Conditions: Obesity Metabolic Disease
Keywords: Obesity Colchicine Inflammation Metabolic Syndrome Dyslipidemia
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 77
Healthy volunteers: yes

Brief summary:
Background:

\- Being overweight may cause low-level inflammation. This inflammation may cause some of the medical problems of obesity, like high blood sugar (diabetes) and heart disease. This study will test whether a medication called colchicine can improve metabolism in adults who are overweight but have not yet developed diabetes.

Objectives:

\- To learn whether colchicine improves sugar regulation and metabolism.

Eligibility:

\- Healthy overweight adults18 to 100 years old.

Design:

* Participants must fast before each visit, including the screening visit.
* Participants will be screened with blood tests,urine tests, medical history, and physical exam. They will have to drink sugar water, and have blood drawn to find out if they are healthy.
* For visit 1, participants will have a medical history and physical exam and answer questions. They will have blood taken with an intravenous (IV) line, give urine sample, and give 2 stool samples..
* Also, subjects will get sugar water through one IV. Blood will be drawn from the other. This measures sugar and insulin levels. During this, participants will lie in a bed and can watch TV.
* Participants will have a full-body X-ray, lying on a table while a camera passes over them. They will also have an abdominal CT scan, lying on a table that moves through a ring that takes pictures.
* Participants will have a small fat tissue sample taken from their abdomen. It is like getting a mini-liposuction.
* Participants will be given the study drug or placebo. They will take it twice daily for 3 months.
* For visit 2, participants will have blood tests, urine tests, medical history, and physical exam.
* For visit 3, participants will repeat the tests in visit 1.

Detailed description:
Obesity affects one-third of the adult U.S. population and is a major risk factor for the development of type 2 diabetes and cardiovascular disease. Mouse models and human data suggest that obesity-induced chronic inflammation is one mechanism promoting obesity-associated comorbid conditions. In obesity, innate immunity is activated by circulating molecules such as fatty acids and cholesterol crystals bind to nucleotide-binding oligomerization (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) receptors in adipocyte tissue macrophages (ATMs). This binding stimulates NLRP3 oligomerization, inflammasome formation, and proinflammatory cytokine activation. The resultant inflammatory cascade leads to insulin resistance and decreased pancreatic beta-cell reserve. It has been proposed that the suppression of this chronic low-level inflammatory state may impede the onset of diabetes and cardiovascular disease.

Recent studies have shown colchicine, a potent microtubule inhibitor commonly used for the treatment of gout and some rare inflammatory conditions, disrupts intracellular localization of NLRP3, thereby blocking inflammasome assembly. As there are limited medical therapies proven effective to improve obesity-related metabolic dysregulation, we propose to determine the efficacy of colchicine 0.6 mg twice daily in non-diabetic obese adults with metabolic syndrome. We will conduct a randomized, double-blinded, placebo-controlled pilot trial of colchicine in forty subjects. We will study changes in insulin resistance, beta-cell reserve, and systemic inflammation. Using adipose tissue obtained from biopsies, we will also study colchicine s local effects on inflammation and insulin resistance. Should results prove promising, this pilot study will allow determination of the sample size needed for an adequately powered study of the effects of colchicine in obese adults with metabolic syndrome.

Seven patients with diet-controlled type 2 diabetes will be given open-label colchicine and followed as described above. We also plan to perform baseline evaluations on 40 subjects who are not eligible for the treatment protocol. This group will consist of non-obese adults, obese adults who are not insulin-resistant, and adults with diet-controlled type 2 diabetes.

Arms:
arm 1: Experimental treatment with placebo capsules identical in appearance to the experimental colchicine preparation arm 2: Experimental treatment with colchicine capsules identical in appearance to the experimental placebo preparation arm 3: Participants with Diet-controlled Type 2 Diabetes who were assigned to Open-label treatment with colchicine. These participants were not randomized and were not part of the randomized controlled trial. arm 4: Participants without obesity seen only for the evaluation component of the study. Such participants are a control group for cross-sectional analyses of baseline data from the experimental cohort. arm 5: Participants with obesity seen only for the evaluation component of the study. Such participants are a control group for cross-sectional analyses of baseline data from the experimental cohort. These participants were found not eligible for randomization. arm 6: Participants with Diet-controlled Type 2 Diabetes seen only for the evaluation component of the study. Such participants are a control group for cross-sectional analyses of baseline data from the experimental cohort.

Interventions: intervention 1: Colchicine 0.6Mg Cap intervention 2: Placebo capsules given intervention 3: Colchicine 0.6Mg Tab
Intervention descriptions: intervention 1: Colchicine 0.6 mg given twice daily intervention 2: Placebo capsules given twice daily intervention 3: Open-label colchicine

Protocol document:
Prot_SAP_000.pdf: 
1 
 
NICHD Human Subjects Research Protocol 
 
Date of this version: 
August 7, 2018 
Project Number 
14-CH-0119 
 
IND/IDE Number
 
WITHDRAWN120722 
 
IND/IDE Holder  
To: 
Karim Calis, PharmD, Chair, IRB, NICHD  
Recommended by:  
 
, Branch Chief, PEMG, NICHD 
 
 
, Clinical Director, NICHD 
 
 
, Clinical Director, NHLBI 
 
 
, Clinical Director, NIDDK 
 
 
, Clinical Director, CC 
Subject: 
Protocol Amendment: 
Pilot study of the effects of colchicine in non-diabetic adults with 
metabolic syndrome 
 
Identifying words: 
• Disease(s): Metabolic syndrome, obesity, dyslipidemia, inflammation 
• Population:  Non-diabetic adults with Metabolic Syndrome 
• Other:  
colchicine, NLRP3, cryopyrin, NALP3 
 
Principal Investigator: 
*Jack A. Yanovski, MD, PhD 
SGO/DTM/NICHD 
 
Lead Associate Investigator:  *Andrew Demidowich, MD 
OCD/NICHD 
 
Accountable Investigator:  
Jack A. Yanovski, MD, PhD 
SGO/DTM/NICHD 
 
*May obtain consent from participants 


2 
 
Study type (check all that apply): 
                Archived biological specimens/medical information 
                Natural history; definition of phenotype, genotype/phenotype correlation 
       x       Prospective linkage/gene identification, NOT providing information to participants 
                Prospective linkage/gene identification, providing information provided to participants  
                Social science; assessments of knowledge, attitudes and behavior 
                Genetic counseling 
       x       Drugs or devices 
                Gene transfer 
                Other interventions 
 
  
Estimated Duration of study: 3 years 
 
Subjects of Study: 
   
 
 
 
  
  
Description 
Number 
Sex 
Age 
Adults screened for protocol 
- 
Screened but not enrolled 
- 
Non-diabetic obese adults with metabolic 
syndrome randomized to colchicine or placebo 
- 
Studied, but not randomized (Evaluation-only) 
- 
Open-Label T2DM arm 
250 
163 
40 
 
40 
7 
M, F 
 ≥ 18 
 
Project uses ionizing radiation: Yes 
 
Medically indicated or research? Research 
 
Project involves use of durable power of attorney: No 
 
Offsite project: No 
 
  
 
 
Research participants to be seen at: 
      x        NIH only*  
 
 
                Off-site only 
 
 
                Both NIH* and off-site 
*Includes participants who physically come to the NIH Clinical Center and/or for whom 
specimens/data are analyzed by Clinical Center departments. If participants will be seen 
at NIH, a Medical Advisory Investigator must be indicated on the 1195 form, unless this 
is a social science project with no clinical interventions. 
 
 
Collaborative Project: 
No. 
 
 


3 
 
Précis: 
 
Obesity affects one-third of the adult U.S. population and is a major risk factor for the development 
of type 2 diabetes and cardiovascular disease.  Mouse models and human data suggest that obesity-induced 
chronic inflammation is one mechanism promoting obesity-associated comorbid conditions.  In obesity, 
innate immunity is activated by circulating molecules such as fatty acids and cholesterol crystals bind to 
nucleotide-binding oligomerization (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) 
receptors in adipocyte tissue macrophages (ATMs).  This binding stimulates NLRP3 oligomerization, 
inflammasome formation, and proinflammatory cytokine activation.  The resultant inflammatory cascade 
leads to insulin resistance and decreased pancreatic beta-cell reserve.  It has been proposed that the 
suppression of this chronic low-level inflammatory state may impede the onset of diabetes and 
cardiovascular disease. 
Recent studies have shown colchicine, a potent microtubule inhibitor commonly used for the 
treatment of gout and some rare inflammatory conditions, disrupts intracellular localization of NLRP3, 
thereby blocking inflammasome assembly.  As there are limited medical therapies proven effective to 
improve obesity-related metabolic dysregulation, we propose to determine the efficacy of colchicine 0.6 mg 
twice daily in non-diabetic obese adults with metabolic syndrome. We will conduct a randomized, double-
blinded, placebo-controlled pilot trial of colchicine in forty subjects.  We will study changes in insulin 
resistance, beta-cell reserve, and systemic inflammation.  Using adipose tissue obtained from biopsies, we 
will also study colchicine’s local effects on inflammation and insulin resistance.  Should results prove 
promising, this pilot study will allow determination of the sample size needed for an adequately powered 
study of the effects of colchicine in obese adults with metabolic syndrome. 
Seven patients with type 2 diabetes will be given open-label colchicine and followed as described 
above. We also plan to perform baseline evaluations on 40 subjects who are not eligible for the treatment 
protocol. This group will consist of non-obese adults, obese adults who are not insulin-resistant, and adults 
with diet-controlled type 2 diabetes.  


4 
 
Table of Contents 
 
I. 
Introduction 
6 
II. 
Study Objectives 
13 
III. 
Specific Aims and Hypotheses 
14 
IV. 
Study Design and Methods 
15 
A. Subject Eligibility 
15 
B. Subject Enrollment 
20 
C. and D. Clinical evaluation and Research Testing/Treatment 
20 
E. Biological Specimens 
26 
F. Molecular Genetic Analysis of DNA 
29 
G. Approved Drugs 
29 
H. Unapproved Drugs 
29 
I. Sharing of Data with Subjects 
29 
J. Questionnaires/Psychological instruments 
30 
K. Genetic Counseling 
30 
L. Follow-up of Patients 
30 
M. Conditions for Discharge from Protocol 
30 
V. 
Analysis of the Study/Oversight 
31 
A. Clinical Description 
31 
i.  
Study Administration, Data Collection, Management, and Storage 
31 
ii.  
Publication of Research Findings 
32 
iii.  
Statistical Analysis of the Data 
32 
iv.  
Monitoring Subjects and Criteria for Withdrawal 
33 
v. 
Stopping Rules 
33 
B. Molecular Studies 
34 


5 
 
VI. 
Determination of Sample Size 
34 
VII. 
Human Subjects Protection 
35 
A. Rationale for Subject Selection 
35 
B. Participation of Vulnerable Populations 
36 
C. Screening Methodology 
36 
D. Risk/Benefit Analysis 
37 
E. Privacy and Confidentiality Provisions 
45 
F. Compensation 
46 
G. Consent Procedures 
46 
H. Pharmaceutical, Biologic, and Device Info 
47 
I. Recruitment Strategies 
49 
J. Existing Data 
49 
K. Criteria for Withdrawal from Study 
49 
L. Re-evaluation of Study 
51 
M. Collection, monitoring, analysis and reporting of adverse events 
51 
a. Waiver of Reporting of Anticipated Non-UP adverse events and 
minor protocol deviations 
52 
b. Plan to monitor and report adverse events 
54 
c. DSMB 
54 
N. IND Monitoring Plan 
54 
VIII. 
Appendices 
58 
IX. 
References 
88 


6 
 
Introduction: 
 
Obesity is a serious disorder that affects approximately one-third of the adult U.S. population and is 
a major risk factor in the development of type 2 diabetes (T2DM), hypertension, dyslipidemia, and 
cardiovascular disease.1-3 The pathophysiology underlying the relationship between obesity, insulin 
resistance, and cardiovascular disease is not fully understood, but numerous studies give evidence that 
inflammation plays a prominent role.  
 
Mouse models of diet-induced and genetically-induced obesity show increased levels of 
inflammatory cytokines, including interleukin (IL)-1β, and IL-18.4  Further, injecting wild-type mice with 
IL-1β decreases insulin sensitivity, whereas IL-1β null mice are protected from insulin resistance after a 12 
week high fat diet (HFD)5.   
Cross-sectional human studies also implicate inflammation in the development of insulin resistance 
and cardiovascular disease.  Data from NHANES III indicate that inflammation is positively correlated with 
BMI6 and the presence of metabolic syndrome (MetS).  Individuals with MetS had more inflammation than 
those without MetS. Higher C-reactive protein (CRP) levels were seen with increasing components of MetS.  
Inflammatory cytokine levels, such as IL-1β, IL-6, and IL-18, were also positively correlated with BMI.7  In 
the Women’s Health Initiative trial, elevated levels of hsCRP and IL-6 were associated with increased risk 
for T2DM and vascular events in apparently healthy postmenopausal women.8,9  Conversely a reduction in 
body weight, either via lifestyle modification or bariatric surgery, lead to decreased levels of inflammation 
and insulin resistance.10,11  Other large cross-sectional studies have also confirmed a relationship between 
inflammation and metabolic abnormalities12,13 and the development of coronary artery disease.14-17 
 
The sources of the chronic low-grade inflammation of obesity arise from multiple organs, but it 
appears that adipose tissue (AT) itself is a large contributor to the inflammatory process.  AT consists of 
adipocytes and the stromal vascular fraction (SVF), which includes fibroblasts, vascular tissue, and adipose 
tissue macrophages (ATM).  In lean individuals, macrophages comprise less than 10% of the cells in AT.18  
The fat cells themselves are smaller in volume and secrete higher levels of adiponectin and omega-3 fatty 
acids, which predispose the macrophages to differentiate to an anti-inflammatory M2 state.  M2 macrophages 
release immunosuppressive cytokines, such as IL-10 and TGFβ, which act on fat and muscle tissue to 
enhance insulin sensitivity.19 However, in obese individuals, adipocytes are both greater in volume and 
number, leading to inefficient triglyceride storage and increased levels of circulating fatty acids and 
ceramides.20  These molecules attach to the pattern recognition receptors in ATMs, which stimulate 
differentiation to the pro-inflammatory M1 phenotype.21  Chronic inflammation ensues, with an increased 
release of chemokines and cytokines including TNFα, IL-1β, IL-6, IL-18, plasminogen activator inhibitor-1 
(PAI-1), monocyte chemoattractant protein-1 (MCP-1), and reactive oxygen species (ROS).21-23  These 


7 
 
factors further augment adipose tissue inflammation by recruiting additional ATMs as well as B and T 
cells.24    
The resultant inflammation is thought to lead to insulin resistance through several concomitant 
pathways.  GLUT4 mediates glucose uptake in adipocytes and skeletal muscle and is integral in glucose 
homeostasis.  In insulin resistant (IR) states, GLUT4 expression in AT is downregulated, and insulin-
stimulated GLUT4 transport to the plasma membrane is impaired.25  Additionally, the chronic inflammatory 
state leads to serine phosphorylation and deactivation of insulin receptor substrate-1 (IRS-1), an important 
downstream mediator of the insulin receptor, by IKK-β.26  IRS-1 expression is downregulated as well.   
Interestingly, Lumeng et al observed that in co-cultured adipocyte and macrophage cells this phenomenon 
was partially reversed when treated with anti-inflammatory TNFα neutralizing antibodies.25    
Moreover, low-grade systemic inflammation can impair pancreatic islet cell functioning and insulin 
secretion.  In early stages of β-cell dysfunction, inflammatory cytokines disrupt the proper intracellular 
calcium storage and flux necessary for adequate insulin secretion.27,28  Chronically, inflammatory signaling 
via the NF-kB and mitogen-activated protein kinase (MAPK) pathways leads to mitochondrial stress, 
reactive oxygen species (ROS) formation, and eventual β-cell apoptosis.29,30 
 
NLRP3 mediates inflammatory activation in obesity 
 
Leukocytes express pattern recognition receptors on their cell surface which allow for induction of a 
rapid inflammatory response to pathogen-associated molecular patterns.  These components of the innate 
immune system, allow for rapid activation of cell-signaling pathways and production of a pro-inflammatory 
cytokine cascade in response to infection.  Similarly, members of the NOD-like receptor (NLR) family can 
recognize endogenous molecules (e.g. free fatty acids, ceramides, urate crystals, ATP) released during cell 
damage and stimulate a robust inflammatory response.31 
 
A member of the NLR family, the NLRP3 (Nod-like receptor family, pyrin domain containing 3) 
inflammasome has been implicated as the major source of chronic inflammation seen in obesity.  NLRP3 
(also known as cryopyrin or NALP3) is primarily expressed in monocytes and macrophages, with little 
production seen in adipocytes or other leukocytes.11,32  Upon binding with a “danger signal,” NLRP3 
receptors oligomerize in the cytosol with procaspase-1 via the adaptor protein ASC (apoptosis-associated 
speck-like protein containing a caspase recruitment domain; also known as PYCARD).  The formation of 
this inflammasome autocatalytically cleaves the cysteine protease procaspase-1 to its active form, caspase-1, 
which in turn cleaves inactive pro-IL-1 and pro-IL-18 into their active forms.33  IL-1β initiates the acute 
phase response and triggers the production and secretion of other pro-inflammatory cytokines, such as TNFα, 


8 
 
IL-6, and MCP-1, resulting in a progressively amplified cytokine network.34  IL-18 also induces the 
production of a number of cytokines, chemokines, and cell-adhesion molecules.35 
 
Obesity and T2DM are associated with elevated circulating levels of danger-associated molecular 
patterns (DAMPs), such as free fatty acids and ceramides.36,37  When human macrophages are cultured with 
saturated fatty acids, IL-1β and IL-18 production increases, but such increases can be abrogated in 
macrophages knocked out for NLRP3, ASC, or caspase-1.  However, knocking out a different Nod-like 
receptor, NLRC4, has no effect.5  Likewise, ceramides, derived from the metabolism of long-chain saturated 
fatty acids, also activate caspase-1 and IL-1β production in human wild-type macrophages, but not in 
NLRP3-knockouts.11 
In vivo mouse models demonstrated similar results.  Nlrp3 and IL1b expression in AT is positively 
correlated with body weight and adiposity in mice, and food restriction results in significant decreases in 
their expression.11  Knocking out components of the NLRP3 inflammasome (e.g. Nlrp3-/-, ASC-/-, caspase-1-/- 
and lL1b-/- mice) does not affect baseline glucose metabolism and insulin sensitivity, but prevents the 
development of insulin resistance and inflammatory cytokine expression during a protracted HFD state.4,5,11,38  
Additionally, ablation of the NLPR3 inflammasome results in markedly smaller adipocytes, elevated levels 
of adipose GLUT4 and adiponectin, with decreased inhibition of IRS-1.11,39  Caspase-1 knockouts also 
demonstrate increased fat oxidation and gain significantly less bodyweight than wild type mice during a 10-
week HFD regimen, despite similar food intake.4  Interestingly no changes in triglyceride or cholesterol 
levels are seen in obese Nlrp3 knockout mice.11 
In humans, metabolically unhealthy obese individuals have greater levels of NLRP3 activity, IL-1β 
expression, AT macrophages, and regulatory T cells (Tregs) in their visceral adipose tissue (VAT) than either 
metabolically healthy obese or lean individuals.   Weight loss in obese subjects with T2DM leads to 
enhanced insulin sensitivity and decreased mRNA expression of IL1B and NLRP3 in subcutaneous adipose 
tissue (SAT).11 
Other circulating molecules seen in models of diet-induced obesity have been found to be potent 
NLRP3 activators.  Oxidized low-density lipoprotein (LDL) and cholesterol crystals increase NLRP3 
inflammasome formation in mice, leading to macrophage activation and IL-1β secretion.  Conversely, 
ablation of the inflammasome reduces early atherosclerosis in high cholesterol diet-fed mice.40  Monosodium 
urate (MSU) crystals, seen in gout and obesity, can also act as a danger signal by stimulating the NLRP3 
inflammasome.41,42   
The progression from insulin resistance to T2DM involves pancreatic inflammation, destruction, and 
reduced pancreatic β-cell reserve.43,44  In a study by Youm, et al, chronically DIO mice had greater levels of 
inflammation, islet fibrosis, and β-cell death than their lean chow-fed littermates, whereas DIO Nlrp3-/- mice 
were protected from these untoward effects.  Consistent with this finding, the DIO Nlrp3-/-mice had lower 


9 
 
fasting glucose and higher fasting insulin levels than their WT counterparts, suggesting that NLRP3 plays an 
important role in both early (i.e. peripheral insulin resistance) and late (i.e. pancreatic beta cell destruction) 
stages of metabolic dysfunction.38 
 
Anti-inflammatory agents in obesity 
 
 
If inflammation is the root cause of obesity-related metabolic dysregulation, then anti-inflammatory 
agents should show benefit.  This has been the case for some mouse models of obesity.  HFD mice treated 
with a neutralizing IL-1β antibody demonstrate significant improvement of glycemic control and beta cell 
function,29 with no effect on weight gain or food intake.45  Given prophylactically, IL-1β antibody treatment 
helps prevent the onset of fasting hyperglycemia and insulin resistance in HFD mice.  IL-1 receptor 
antagonist (IL-1Ra) treatment of DIO mice leads to similar results, with decreased β-cell apoptosis, increased 
β-cell proliferation, and improved glucose-stimulated insulin secretion.45,46  Studies inducing blockade of 
other inflammatory cytokines or pathways in mice, including TNFα47, IL-648, MCP-149, and NF-kB50 have 
also demonstrated favorable metabolic results from reduction of inflammatory processes. 
 
However, such robust results have not been replicated in human clinical trials.  Blockade of TNFα 
had no effect on metabolic parameters T2DM participants47 and only marginal impact in non-diabetic insulin 
resistant subjects.51  Similar findings were seen when using aspirin or the IL-1β antibody canakinumab.52-54  
A different monoclonal IL-1β antibody, gevokizumab, has led to improvements in HbA1c, but not beta-cell 
secretory function or insulin sensitivity in preliminary trials.55  Only anakinra, a recombinant human IL-1Ra, 
has demonstrated any significant benefit, with an improvement in beta-cell secretory function and decrease in 
Hemoglobin A1c in diabetic subjects,56 but not in subjects with impaired glucose tolerance.57 Furthermore, 
anakinra did not affect insulin sensitivity as measured by insulin clamp or HOMA-IR in either study.  
 
While these results are disappointing, they are not wholly unexpected. The machinery involved in 
obesity-induced chronic inflammation is complex.  Cytokines may play complementary, if not redundant, 
roles in promoting inflammation.  Chemokines and endothelial adhesion molecules play integral roles in the 
sustained inflammatory response by facilitating chemoattraction, diapedesis, and migration of additional 
leukocytes to adipose and pancreatic tissues.  For this reason, eliminating a single cytokine may not be 
sufficient to demonstrate significant changes in glucose homeostasis. 
 
Colchicine in preclinical trials 
 
Colchicine remains an intriguing treatment for obesity-associated chronic inflammation because it 
mitigates inflammation through several mechanisms.  Colchicine is a tricyclic alkaloid, extracted from the 


10 
 
flowering plants Colchicum autumnale and Gloriosa superba.58  It has been used to treat gout for over 2000 
years, although the purified form was brought to prominence at the end of the 19th century.59  Colchicine 
exerts its effects by binding in a poorly reversible manner to tubulin, thereby interfering with microtubule 
formation and elongation.  At higher concentrations colchicine promotes depolymerization of microtubules.60  
 
Classically, colchicine was thought to exert its anti-inflammatory actions by inhibiting neutrophil 
chemotaxis and diminishing release of lysosomal enzymes during phagocytosis.  Colchicine also decreases 
leukocyte recruitment by blocking the production and/or release of chemotactic molecules leukotriene B4 
and crystal-derived chemotactic factor (CCF).61   Leukocyte recruitment is further impaired by the inhibition 
of adhesion molecules, such as E-selectin and P-selectins on endothelial cells, L-selectin on leukocytes, 
vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1)61,62.  Surface 
expression of the TNFα receptor in macrophages is also reduced with colchicine, as is neutrophil superoxide 
anion production.63,64  Recent studies also suggest that colchicine may modulate expression of genes involved 
in inflammation or cell migration.65,66  
Notably, oligomerization and activation of the NLRP3 inflammasome is disrupted by 
colchicine.  Microtubules mediate NLRP3 inflammasome formation by transporting ASC and NLRP3 into 
close proximity to each other in the cell, and inhibition of microtubule formation by colchicine has been 
shown to significantly inhibit NLRP3 activation in macrophages both in vitro and in vivo.41,67 
 
Colchicine in human studies 
 
 
Colchicine is currently FDA-approved for the treatment of gout and Familial Mediterranean Fever,68 
and has shown efficacy in other inflammatory conditions.69-71 As inflammation has been hypothesized to play 
a role in the development of cardiovascular disease, several clinical studies have recently examined the 
efficacy of colchicine in cardiovascular-related conditions.  Colchicine 0.5 mg twice daily decreased hsCRP 
levels after one month of treatment in subjects with stable coronary artery disease already on a statin and 
aspirin,72 although this was not seen in patients with acute coronary syndrome or acute stroke.73  Subjects 
with paroxysmal atrial fibrillation, randomized to colchicine after radiofrequency ablation, had decreased 
atrial fibrillation recurrence at 3 months and more substantial post-treatment decrements in hsCRP and IL-6 
levels than those randomized to placebo.74 Colchicine has also demonstrated considerable benefit in reducing 
incidence of recurrent pericarditis75-77 and post-pericardectomy syndrome.78,79 
 
Notably, colchicine has great promise preventing acute coronary syndrome in high risk individuals.  
Among the 532 subjects with stable coronary artery disease on a statin and aspirin and/or clopidogrel, 30% 
of whom had Type 2 diabetes mellitus (T2DM), those randomized to colchicine demonstrated a significantly 
decreased primary composite endpoint of acute coronary syndrome, out-of-hospital cardiac arrest or stroke at 


11 
 
3 years as compared to placebo.80  Another study examined restenosis rate in patients with T2DM 
undergoing percutaneous coronary intervention with bare metal stent placement.  Those randomized to 
colchicine had significantly fewer restenotic events and less neointimal hyperplasia as compared to subjects 
taking placebo.81  Subjects in these studies, many of whom had features of the metabolic syndrome, tolerated 
colchicine well, with the most common side effect being diarrhea/gastrointestinal disturbances (7 – 16%).  
In addition to predisposing to cardiovascular disease, inflammation is thought to play a role in 
insulin resistance.  However, colchicine’s effect on glucose or insulin in individuals with metabolic 
dysregulation is unknown.  Early studies on colchicine suggested that it worsened glucose control by 
inhibiting early and late phase insulin secretion.  However, these studies were done in healthy adults, and the 
treatment duration was less than two weeks.82,83  In subjects with Familial Mediterranean Fever chronically 
on colchicine for 2-13 years, data from frequently-sampled intravenous glucose tolerance testing (FSIVGTT) 
and oral glucose tolerance testing did not demonstrate any differences in fasting insulin or glucose levels, 
early-phase insulin release, or glucose dynamics, as compared with age-matched healthy volunteers.84  
Additionally, neither a Cochrane Database review nor the Colcrys prescriber information insert show 
hyperglycemia as a potential adverse effect of colchicine use.68,85 
 
By blocking NLRP3 inflammasome formation and cytokine production, a plausible mechanism 
exists by which colchicine could improve glucose homeostasis and insulin resistance in obese individuals 
who have evidence for inflammation.  Improvement in metabolic dysregulation may also improve 
cardiovascular risk factors in individuals with MetS, although this has not yet been formally evaluated using 
colchicine.  Consequently, colchicine is an intriguing treatment option for metabolic dysregulation and 
warrants investigation to determine its potential health benefits in obese insulin-resistant individuals. The 
results of such a study also have the potential to advance our knowledge regarding the interplay of 
inflammation and metabolic dysregulation in man.  
 
Adipocyte Ex-Vivo Studies 
 
Whole body insulin-mediated glucose uptake depends primarily on glucose uptake in three organ 
systems: liver, adipose, and muscle.  Upon binding to the insulin receptors in peripheral tissues, insulin 
signaling increases the number of insulin-stimulated glucose transporters (GLUT4) at the cell surface and 
allows augmented glucose translocation across adipocyte and muscle plasma membranes.  However, most 
research on the kinetics of insulin signaling pathways and the studies that examine how inflammation 
perturbs these pathways have been performed largely in either non-human models86-88 or cultured 3T3-L1 
mouse cells.89-91 Preliminary studies have shown that these kinetic models are inadequate to capture insulin 
dynamics at the level of the human adipocyte because they do not recapitulate the multiple phases of GLUT4 
trafficking. While in vivo human studies would serve as the most appropriate representation of insulin 


12 
 
kinetics, the logistics of these measurements make them unrealistic. Therefore, ex vivo experiments may 
instead serve as a more reasonable portrayal of the kinetics of the adipocyte’s response to insulin within 
obese insulin-resistant subjects with chronic inflammation. 
 
Thus, collaborating with the NICHD Section on Membrane and Cellular Biophysics as a part of the 
NICHD Director’s Investigator Award, we have initiated investigations of the effects of colchicine on insulin 
sensitivity locally in the subcutaneous adipose tissue. Dr. Chad McCormick, a member of this collaboration, 
is examining insulin kinetics in coded adipocyte biopsy samples obtained from our subjects by creating a 
novel reporter system in which we transfect subjects’ adipocytes with a HA-pHTomato-GLUT4-mEGFP 
plasmid to quantify GLUT4 translocation to the cell surface after maximal insulin stimulation in culture.  
 
Additionally, it has been recently hypothesized that individual adipocytes do not exhibit variable 
degrees of insulin sensitivity along a spectrum, but rather manifest a binary insulin-sensitive or insulin-
resistant state.92 Consequently, insulin-resistant subjects have some insulin-sensitive adipocytes that respond 
to insulin in a similar fashion as those of lean, healthy individuals, but the percentage of responsive cells in 
insulin-resistant individuals is much lower than that of lean, healthy individuals.92 Dr. McCormick is 
utilizing quantitative immunofluorescence microscopy to investigate whether local SAT inflammation 
promotes IR states by changing insulin-sensitive adipocytes into insulin-refractory adipocytes [Figure 1]. As 
Akt is phosphorylated upon insulin binding to the insulin receptor, we are able to visualize and quantify 
phospho-Akt (phosphorylation at Thr308; pThr308). Ultimately this allows us to evaluate insulin sensitivity 
at the cellular level. By also staining the tissue with anti-CD11c antibody to identify M1 pro-inflammatory 
macrophages as well as CD68, a universal macrophage marker, we are able to assess whether adipocytes in 
close proximity to activated macrophages lack phospho-Akt (pThr308) and therefore exhibit suppressed 
insulin signaling.  
 
 


13 
 
  
 
 
 
The subjects evaluated by the aforementioned methods in our protocol thus far consist only of obese 
insulin-resistant non-diabetics.  Because of the potentially significant findings and novel strategies to 
evaluate local insulin sensitivity in human SAT, it would be worthwhile to investigate how these results 
compare with healthy non-insulin resistant volunteers and subjects with T2DM.   
 
II. Study Objectives: 
 
We propose a pilot study of the effects of colchicine in obese non-diabetic adults with metabolic 
syndrome to determine if colchicine treatment can improve metabolic and inflammatory parameters, both 
locally and systemically, independent of weight loss. This pilot study will determine the sample size needed 
for an adequately powered larger study in the future. 
 
We also propose enrolling additional subjects who do not qualify for the protocol to evaluation only. 
This group will consist of non-obese and obese adults without significant insulin resistance and/or 
inflammation as well as subjects with diet-controlled T2DM. They will not be randomized or receive study 
medication.  The results from these controls will allow us to determine insulin kinetics in SAT over the entire 
spectrum of insulin sensitivity.  
 
Subjects with T2DM have more severe metabolic abnormalities and typically higher inflammatory 
levels, but their pancreatic function may possibly be past the point of reversibility.  Therefore, it is unclear 
whether such subjects would be the most likely or least likely group to derive benefit, if any, from colchicine.  
We propose to enroll seven diet-controlled subjects with T2DM to an open-label colchicine arm. Results 
A 
B 
Figure 1. (A) Immunofluorescence imaging of a 3µm Z-slice of subcutaneous adipose tissue from a subject. Blue 
staining represents AKT p308 (insulin sensitivity), red represents CD68 (macrophages), and green represents 
CD11c (M1 pro-inflammatory macrophages). Most adipocytes have Akt p308 staining, but some are notably 
absent. (B) Zoomed-in images of activated M1 macrophages on Bright field and confocal merge 
immunofluorescent microscopy.  Many of the adipocytes surrounding the M1 macrophages lack Akt p308 staining 
and are insulin-refractory. 


14 
 
from this arm will allow us to determine the sample size that might be needed if a future study for the effects 
of colchicine in T2DM were to be carried out. 
 
III. Specific Aims and Hypotheses:  
 
Through this randomized, double-blind, placebo-controlled clinical trial, we will obtain pilot data for the 
following aims and hypotheses: 
 
1. 
Aim 1: To explore changes in insulin sensitivity, as measured by FSIVGTT, among obese 
non-diabetic adults following long-term colchicine administration. 
Hypothesis 1: We hypothesize that obese non-diabetic adults on colchicine 0.6mg bid for 3 
months will exhibit significant improvements in insulin sensitivity compared with placebo, 
independent of weight loss.  We also hypothesize that reductions in systemic inflammation, 
as measured by hsCRP, will moderate this relationship. 
2. 
Aim 2: To explore changes in other parameters of glucose homeostasis, among obese non-
diabetic adults following long-term colchicine administration. 
Hypothesis 2: Using data from the FSIVGTT, we hypothesize that obese non-diabetic adults 
on colchicine will exhibit significant improvements in acute pancreatic reserve (as measured 
by acute insulin response to glucose (AIRg)) and glucose homeostasis (as measured by the 
Disposition Index). We also hypothesize that insulin resistance as measured by HOMA-IR 
will demonstrate improvement in colchicine-treated subjects.  
3. 
Aim 3: To explore changes in cardiovascular risk factors among obese non-diabetic adults 
following long-term colchicine administration. 
Hypothesis 3: We hypothesize that colchicine-treated subjects will demonstrate significant 
improvements in cardiovascular risk factors and other lipid parameters, including blood 
pressure, LDL, HDL, Lp(a), fatty acid levels, uric acid, hemoglobin A1c, and fasting plasma 
glucose as compared with placebo-treated subjects. 
4. 
Aim 4: To explore changes in inflammation among obese non-diabetic adults following 
long-term colchicine administration. 
Hypothesis 4a: We hypothesize that colchicine-treated subjects will demonstrate significant 
improvements in systemic inflammatory markers as well as leukocyte/endothelial adhesion 
markers. 
Hypothesis 4b: We hypothesize that colchicine-treated subjects will demonstrate significant 
improvements in local adipose tissue inflammation. 


15 
 
5. 
Aim 5: To explore insulin-dependent GLUT4 dynamics locally in human adipocytes across 
the spectrum of insulin sensitivity.  
Hypothesis 5a: We hypothesize that colchicine-treated subjects will demonstrate significant 
improvements in adipose insulin-dependent GLUT4 kinetics in vitro. 
 
IV. Study Design and Methods: 
 
A. Subject Eligibility: All adults who meet the inclusion and exclusion criteria as listed below and who 
can attend all needed study visits at the NIH Clinical Center will be eligible: 
 
I. 
Inclusion Criteria for subjects randomized to colchicine or placebo: 
 
Subjects will qualify for randomization to colchicine or placebo if they meet the following criteria: 
1. 
Good general health.  In general subjects should take no medications.  However, individuals 
taking medications for obesity-related co-morbid conditions, who have not had changes in 
dosage for more than 3 months, may be included, at the discretion of the principal 
investigator. 
2. 
Obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, but weight less than 450 lbs in 
order for subjects to undergo Dual-Energy X-ray Absorptiometry (DXA) scanning. 
3.  
Age 18-100 years. 
4.  
Metabolic Syndrome93 
(Any 3 of the following 5): 
a. 
FPG ≥ 100 mg/dl or Impaired Glucose Tolerance (Glucose ≥ 140 mg/dl at 2 hours of 
OGTT) 
b. 
Triglycerides ≥ 150 mg/dl, or on treatment 
c. 
Waist Circumference: Men ≥ 40 in (≥ 102 cm); Women ≥ 35 in (≥ 88 cm) 
d. 
Reduced HDL-C: Men < 40 mg/dl; Women < 50 mg/dl, or on treatment 
e. 
Hypertension: ≥130 mmHg systolic, or ≥85 mmHg diastolic, or on treatment 
5. 
HOMA-IR ≥ 2.6.  Our goal is to enroll participants who have pre-existing insulin 
resistance.94 
6. 
hsCRP ≥ 2.0 mg/L. We aim to recruit participants with increased baseline level of 
inflammation. Individuals with hsCRP above 2.0 mg/L have been shown to have an 
increased risk for cardiovascular events.16  
 
II. 
Exclusion Criteria for subjects randomized to colchicine or placebo:  


16 
 
1. 
Type 2 diabetes mellitus, as determined by either having: 
a. 
“clear clinical diagnosis” of diabetes, such as “a patient in a hyperglycemic crisis or 
classic symptoms of hyperglycemia and a random plasma glucose ≥200 mg/dL” 
b. 
two of the following three: 
 
i. 
fasting plasma glucose ≥ 126 mg/dL 
ii. 
Hemoglobin A1c ≥ 6.5% 
iii. 
An oral glucose tolerance test glucose concentration of ≥ 200 mg/dL at 2 
hours. 
c. 
one of the above three criteria (bi.-biii.) meeting the T2DM cutoff on two different 
days. 
If only one of the above three criteria (bi.-biii.) meet the T2DM threshold during the 
Screening Visit, that test will be repeated on another day to determine if the subject has 
T2DM or not.  As per ADA guidelines, “The diagnosis [of T2DM] is made on the basis of 
the confirmed test.”95 
 
Moreover, because HbA1c has been shown to be higher in African Americans (AA) 
as compared to other races for the same glycemia, non-diabetic AA may be unfairly 
excluded by their HbA1c alone.96-98  Therefore, for AA subjects, if their 2 hour OGTT and 
fasting glucoses are in the non-diabetic range, and the HbA1c is < 7.0%, we will consider 
them non-diabetic. 
2. 
Presence of a significant active or chronic illness likely to limit life span and/or increase risk 
of intervention, including renal (GFR ≤ 60 ml/min/1.73m2), cardiovascular, hepatic (other 
than obesity-related steatosis), gastrointestinal, immunologic, endocrinologic (e.g. Cushing 
syndrome), pulmonary (other than either asthma not requiring continuous medication or 
sleep apnea-related disorders), or other disorders at the discretion of the investigators. 
3. 
Recent use of colchicine or anorexiant medications in the last 3 months. 
4. 
Known allergy to colchicine. 
5. 
Previous history of agranulocytosis, gout, or significant myositis. 
6. 
Females who are pregnant, planning to become pregnant, currently nursing an infant, or have 
irregular menses, defined as cycles less than 21 days or greater than 45 days.99 
7. 
Individuals who have current substance abuse or a psychiatric disorder or any other 
condition that in the opinion of the investigators would impede competence, compliance, or 
participation in the study. 
8. 
Subjects who regularly use prescription medications unrelated to the complications of 
obesity, especially those known to affect enzymes involved in colchicine metabolism, such 


17 
 
as CYP3A4 or P-glycoprotein (P-gp) (see Appendix B1).  Oral contraceptive use will be 
permitted, provided the contraceptive has been used for at least two months before starting 
study medication.  The use of over-the-counter and prescription medications will be 
reviewed on a case-by-case basis; depending on the medication, subjects who have 
continued to take prescription medication or have stopped taking an exclusionary medication 
for at least 3 months prior to study entry may be eligible (see Appendix B2). 
9. 
Participation in a formal weight loss program (e.g. Weight Watchers) or recent weight 
change of more than 3% of body weight in the past two months. 
10. 
Use of anti-inflammatory medications (e.g. prednisone, NSAIDs) chronically or in the last 
7 days prior to fat biopsy.  
11. 
History of keloid formation. 
12. 
Current users of tobacco or nicotine products (e.g. nicotine patch, e-cigarettes). 
 
III. 
Inclusion Criteria for subjects who are evaluated but not eligible for randomization: 
 
Subjects will qualify for the Evaluation-only arm if they meet the following criteria: 
1. 
Good general health.  In general subjects should take no medications.  The use of over-the-
counter and prescription medications will be reviewed on a case-by-case basis; depending on 
the medication, subjects who have continued to take prescription medication or have stopped 
taking an exclusionary medication for at least 3 months prior to study entry may be eligible 
(see Appendix B2). 
2. 
Weight less than 450 lbs in order for subjects to undergo Dual-Energy X-ray Absorptiometry 
(DXA) scanning. 
3.  
Age 18-100 years. 
 
IV. 
Exclusion Criteria for subjects who are evaluated but not eligible for randomization:  
1. 
Type 2 diabetes mellitus that is not well controlled with diet alone: subjects taking an anti-
diabetic medication (e.g. metformin, insulin, sulfonylureas, etc.) or having a Hemoglobin 
A1c > 9.0% 
2. 
Presence of a significant active or chronic illness likely to limit life span and/or increase risk 
of intervention, including renal (GFR ≤ 60 ml/min/1.73m2), cardiovascular, hepatic (other 
than obesity-related steatosis), gastrointestinal, immunologic, endocrinologic (e.g. Cushing 
syndrome), pulmonary (other than either asthma not requiring continuous medication or 
sleep apnea-related disorders), or other disorders at the discretion of the investigators. 
3. 
Recent use of colchicine or anorexiant medications in the last 3 months. 


18 
 
4. 
Females who are pregnant, planning to become pregnant, or are currently nursing an infant.  
5. 
Individuals who have current substance abuse or a psychiatric disorder or any other 
condition that in the opinion of the investigators would impede competence, compliance, or 
participation in the study. 
6. 
Participation in a formal weight loss program (e.g. Weight Watchers) or recent weight 
change of more than 3% of body weight in the past two months. 
7. 
Use of anti-inflammatory medications (e.g. prednisone, NSAIDs) chronically or in the last 
7 days prior to fat biopsy.  
8. 
History of keloid formation. 
9. 
Current users of tobacco or nicotine products (e.g. nicotine patch, e-cigarettes). 
 
V. 
Inclusion Criteria for subjects with diet-controlled T2DM 
Subjects will qualify for the Open Label arm if they meet the following criteria  
1. 
Diet-controlled T2DM, as determined by having all of the following: 
a  
A diagnosis of T2DM (as defined above in Section IV.II.1.). 
b  
Not on any diabetic/hypoglycemic agents 
c  
Not having an alternate cause of hyperglycemia (e.g. T1DM, glucocorticoid-
induced, lipodystrophy, acromegaly, etc.) 
d 
Hemoglobin A1c ≤ 9.0% 
2. 
Good general health.  In general subjects should take no medications.  The use of over-the-
counter and prescription medications will be reviewed on a case-by-case basis; depending on 
the medication, subjects who have continued to take prescription medication or have stopped 
taking an exclusionary medication for at least 3 months prior to study entry may be eligible 
(see Appendix B2). 
3.  
Age 18-100 years. 
4. 
Obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, but weight less than 450 lbs in 
order for subjects to undergo Dual-Energy X-ray Absorptiometry (DXA) scanning. 
5.  
Metabolic Syndrome93 
(Any 3 of the following 5): 
a. 
FPG ≥ 100 mg/dl or Impaired Glucose Tolerance (Glucose ≥ 140 mg/dl at 2 hours of 
OGTT) 
b. 
Triglycerides ≥ 150 mg/dl, or on treatment 
c. 
Waist Circumference: Men ≥ 40 in (≥ 102 cm); Women ≥ 35 in (≥ 88 cm) 
d. 
Reduced HDL-C: Men < 40 mg/dl; Women < 50 mg/dl, or on treatment 


19 
 
e. 
Hypertension: ≥130 mmHg systolic, or ≥85 mmHg diastolic, or on treatment 
6. 
HOMA-IR ≥ 2.6.  Our goal is to enroll participants who have pre-existing insulin 
resistance.94 
7. 
hsCRP ≥ 2.0 mg/L. We aim to recruit participants with increased baseline level of 
inflammation. Individuals with hsCRP above 2.0 mg/L have been shown to have an 
increased risk for cardiovascular events.16  
 
VI. 
Exclusion Criteria for subjects with diet-controlled T2DM 
1. 
T2DM that is not well controlled with diet alone: subjects will not be eligible if they take an 
anti-diabetic medication (e.g. metformin, insulin, sulfonylurea, etc.), or have HbA1c > 9%. 
2. 
Presence of a significant active or chronic illness likely to limit life span and/or increase risk 
of intervention, including renal (GFR ≤ 30 ml/min/1.73m2), cardiovascular, hepatic (other 
than obesity-related steatosis), gastrointestinal, immunologic, endocrinologic (e.g. Cushing 
syndrome), pulmonary (other than either asthma not requiring continuous medication or 
sleep apnea-related disorders), or other disorders at the discretion of the investigators. 
3. 
Recent use of colchicine or anorexiant medications in the last 3 months. 
4. 
Known allergy to colchicine. 
5. 
Previous history of agranulocytosis, gout, or significant myositis. 
6. 
Females who are pregnant, planning to become pregnant, currently nursing an infant, or have 
irregular menses, defined as cycles less than 21 days or greater than 45 days.99 
7. 
Individuals who have current substance abuse or a psychiatric disorder or any other 
condition that in the opinion of the investigators would impede competence, compliance, or 
participation in the study. 
8. 
Subjects who regularly use prescription medications unrelated to the complications of 
obesity, especially those known to affect enzymes involved in colchicine metabolism, such 
as CYP3A4 or P-glycoprotein (P-gp) (see Appendix B1).  Oral contraceptive use will be 
permitted, provided the contraceptive has been used for at least two months before starting 
study medication.  The use of over-the-counter and prescription medications will be 
reviewed on a case-by-case basis; depending on the medication, subjects who have 
continued to take prescription medication or have stopped taking an exclusionary medication 
for at least 3 months prior to study entry may be eligible (see Appendix B2). 
9. 
Participation in a formal weight loss program (e.g. Weight Watchers) or recent weight 
change of more than 3% of body weight in the past two months. 


20 
 
10. 
Use of anti-inflammatory medications (e.g. prednisone, NSAIDs) chronically or in the last 
7 days prior to fat biopsy.  
11. 
History of keloid formation. 
12. 
Current users of tobacco or nicotine products (e.g. nicotine patch, e-cigarettes). 
 
 
B. Subject Enrollment 
Subjects will be enrolled only at the National Institutes of Health Hatfield Clinical Research Center. 
Each subject will be registered using the Clinical Research Information System (CRIS), but will be 
considered enrolled only after the participant signs the study consent form.  
 
C. Clinical evaluation and D. Research Testing, and/or Treatment 
Brief summary of study design: Participants who appear qualified when first contacted will 
undergo an initial screening visit, during which a history and physical examination, initial protocol 
review, body composition DEXA, and screening laboratory assessment will take place.  If after the 
screening visit, the subject still appears qualified he/she will return for a baseline visit, during which 
time baseline labs, Hollingshead questionnaire, FSIVGTT, body composition DEXA (if not 
performed during the Screening Visit), CT abdomen, and SAT biopsy will take place. After 
assessments are complete, participants who qualify for and agree to randomization will be 
randomized to either placebo or colchicine and given an eight week supply of medication.  
Randomized subjects will be called at 1 week, 1 month, and 2 months to assess for adverse events 
and adherence.  Randomized subjects will return for a safety interim visit between 4-8 weeks to 
assess for adverse events by physical exam and laboratory studies, where they will receive another 8 
week supply of study drug.  At 3 months, randomized subjects will return for the final visit for 
repeat physical exam, labs, FSIVGTT, body composition DEXA, CT abdomen, SAT biopsy, and 
exit questionnaire.  For randomized subjects who complete the study, they will be given the option 
to return for another “washout” visit three months later, which will involve the same testing as the 
baseline and final visits.  All study visits will take place at the NIH Clinical Center, Bethesda, MD. 
(Please see Appendices A1-A6) 
 
Subject who qualify for the Evaluation-Only arm will only undergo the Screening and 
Baseline visits as described above. 
 
For the Open Label arm, seven subjects with T2DM will be recruited. They will undergo the 
same visits and testing as in the randomization arm, described above.  For the Open Label arm only, 
pills will be dispensed with a “smart bottle cap” which will be able to record the time and date that 


21 
 
the pill bottle was opened. Specifically, we will purchase the MEMSCaps system 
(http://www.mwvaardex.com/index.php/our-adherence-solutions-data-collection/memscap-tm).  
Each bottle supplied by NIH pharmacy will come with a TrackCap®, with the participant’s subject 
ID number assigned to the specific cap.  At the end of the three months on study drug, when the 
subject returns the study drug bottle and cap, we will download the data directly to an SGO lab 
computer.  No PII or medical record number will be associated with the TrackCap, and only the 
investigators involved in the study (e.g. JY, AD, SB) will have access to the data.   
 
i. 
Initial Contact: Telephone Screen 
For participants who respond to advertisements requesting participants (see below), initial 
recruitment and eligibility screening will occur by telephone. Recruitment will occur on a 
continuous basis until study enrollment is complete.  Eligible subjects will then be scheduled for 
an outpatient screening visit.  Eligible subjects will be mailed paperwork in advance, including 
the NIH medical history form, which will then be reviewed in person with the potential subject 
at the outpatient screening visit. 
 
ii. 
Screening Evaluation 
Complete medical history and physical exam will be performed with weight (in kg) 
measured while the subject wears light clothes and height (in cm) measured in triplicate.  
Subjects will rest for 5 minutes in the seated position with the antecubital fossa supported at 
heart level when blood pressure measurements are made. Body mass index (BMI) will be 
calculated before protocol is signed and current medications reviewed, so that individuals taking 
an exclusionary medication, have a disqualifying medical condition, or are weighing more than 
the maximum weight criterion (450 lbs) can be dismissed before the protocol is reviewed.   
Protocol review and signing of consent forms: For those who may be eligible, the relevant 
consent form (either evaluation-only or randomized study protocol) will be discussed and study 
risks and benefits explained. 
EKG and fasting blood for complete blood count (CBC), acute care, mineral, and hepatic 
profiles, PT/PTT, TSH, Free T4, Total T3, IGF-1, and creatine kinase (CK) will be obtained to 
ensure that the subject is in good general health.  Fasting blood samples for hsCRP, insulin, and 
HbA1c will be obtained, and a 2 hour OGTT-GH will be performed to confirm subject eligibility 
for the study.  Additional samples for peripheral blood mononucleated cell (PBMC) analysis and 
future research and genomic DNA isolation will be obtained.   


22 
 
Urine for urinalysis, urine pregnancy test (female participants only), and urine toxicology 
screen will be obtained to ensure that the subject is in good general health and meets protocol 
entry criteria. 
If a potential subject is noted to meet any of the exclusion criteria, that individual will be 
dismissed without further evaluation and referred to their usual physician for any required 
treatment. 
DXA Scan for body composition analysis and fat mass will be obtained.  DXA involves 
passing a collimated X-ray beam of 40 and 70 KeV through the subject and collecting the X-rays 
that pass through the patient with a standard X-ray detector. Because the delivery and attenuation 
of the X-rays are measured separately for the two principal energies, the procedure allows the 
differentiation of substances in their path if the attenuation coefficients of these substances are 
known. Because the delivery and attenuation of the X-rays are measured separately for the two 
principal energies, the procedure allows the differentiation of substances in their path if the 
attenuation coefficients of these substances are known. The manufacturer specifies that the array 
beam delivers an effective dose of 0.00003rem total body irradiation. Participants will undergo 
DXA scans in the Metabolic Clinical Research Unit (MCRU) using the Lunar iDXA (GE 
Healthcare, Madison, WI, USA) machine. The scan takes approximately 20-30 minutes. An 
external standard, simulating bone, fat, and muscle, is scanned once a week to validate 
measurements. This standard allows calculation of total body fat, muscle, and bone mass, and 
percentage of body fat. 
 
iii. 
Baseline evaluation 
An interval history and physical exam will be performed with weight (in kg), height (in cm), 
and blood pressure measured as above. 
Socioeconomic Status will be determined using the Hollingshead Two-Factor Index of 
Social Position.100 
Fasting blood samples of hsCRP, insulin, HbA1c, free fatty acids, lipid panel, uric acid, and 
serum beta HCG (female participants only) will be obtained. Blood samples will also be 
collected for PBMC analysis, as well as to measure inflammatory cytokines, endothelial 
adhesion molecules, lipoproteins (e.g. Lp(a), oxidized HDL, NMR lipoprotein particle analysis), 
leptin, and adiponectin.  Additional research blood samples will be drawn for storage in a -80oC 
freezer for possible future research. 


23 
 
Two stool samples to save for future analyses will be obtained. Subjects will be asked to fill 
out a paper survey including 24 hour food intake that will be reviewed in-person with an NIH 
nutritionist (see Appendix G). 
Urine sample as described previously. In addition to the urine sample collected on 
admission, we will collect a timed eight hour urine sample, which will be saved for future 
analyses.101,102 
FSIVGTT: As described previously,103-105 two angiocatheters will be placed in the 
antecubital veins, one for the administration of glucose and insulin and the other for blood 
sampling from the contralateral arm. A glucose load of 50% dextrose 0.3 g/kg given as a smooth 
bolus over 2 min is given at time 0 and a bolus of 0.05 U/kg insulin is given just before minute 
20. Blood samples are taken at times -15, -10, -5, -1, then at 2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 25, 
30, 40, 50, 70, 100, 140, and 180 minutes after glucose injection for the measurement of plasma 
glucose and serum insulin concentrations.106,107  Insulin administration is essential for individuals 
with severe insulin resistance to achieve a valid test.108-110  Insulin sensitivity and glucose 
effectiveness will be assessed using Bergman’s minimal model,103 which requires the particular 
times of blood collection that have been specified above.  The principal investigator will be 
notified immediately of any glucose measurement less than 40 mg/dL. The principal investigator 
will use his clinical judgment in developing an appropriate, situation-specific management plan. 
 
CT abdomen-adipose:  To quantify the fat content of the liver, subcutaneous, and visceral 
compartments, subjects will undergo a CT of the abdomen, where slices at only three levels will 
be obtained.  CT scanning parameters are 5-10 mm slice thickness, 0.7-0.98 in-plane pixel 
resolution, and 120 kVp. As previously established liver fat can be reliably quantified from one 
slice, typically in the T12-L1 region.111,112 
In accordance with previous studies, subcutaneous and visceral fat compartments can 
reliably be quantified from slices of the L2-3 and L4-5 levels.113  Using automated software 
developed at the NIH, an algorithm consisting of body masking, noise reduction, adipose tissue 
labeling, VAT and SAT separation, and quantification will be used. The body mask is created by 
a region-growing algorithm on the image background that segments the low intensity pixels 
outside the body and in a second pass, removes the CT table. Once the body mask is created, an 
anisotropic diffusion filter reduces noise and voxels between -274 HU and -49 HU. A contour 
around the outside of the body, the “external contour”, is initialized. Active contour models are 
then used to iteratively modify the external contour to find the inner boundary of the SAT; this 
results in a contour along the abdominal wall, specifically the “internal contour”. The adipose 


24 
 
tissue volume inside the internal contour contributes to the VAT and the adipose tissue volume 
between the external contour and internal contour contributes to SAT.   
In collaboration with James Vucich, NIH Medical Physicist, it was determined that the CT 
scan will deliver an effective dose of 0.031 rem total body irradiation per scan.  As randomized 
and open-label participants will undergo three CT scans and three DEXA scans as part of the 
study, the total effective radiation dose for the study is 0.093 rem. Evaluation-only participants 
will receive one CT and one DEXA scan (total effective radition dose = .031 rem. For all three  
protocol arms, this dose is well below the dose guideline of 5 rem per year established by the 
NIH Radiation Safety Committee for adult research subjects. 
Subcutaneous abdominal adipose tissue biopsy: Abdominal subcutaneous adipose tissue 
samples will be obtained using a mini-liposuction technique (see Appendix C for checklist). 
Subjects will be advised not to use non-steroidal anti-inflammatory drugs (NSAID; e.g. aspirin, 
ibuprofen, etc.) for at least one week prior to and following the procedure. The biopsies will be 
performed by an MD or CRNP on the adult outpatient unit. A mixture of 1:1 lactated Ringers or 
normal saline and lidocaine will be used as a local anesthetic until there is an “orange peel” 
appearance to the skin. A sterile approach will be used to minimize risk of infection. Using 10 or 
20 cc syringes with blunt, fenestrated needles, gentle to-and-fro movements will be used to 
obtain the samples. The contents of the syringe will be transferred onto a 250 Nylon mesh (Nitex 
screen cloth, Sefar America, Depew, NY) and rinsed with 5-10ml normal saline to wash away 
the lidocaine and blood clots as much as possible. Fifteen grams of subcutaneous adipose tissue 
samples will be used to assess changes in adipocyte size and the expression of proteins involved 
in inflammation. Subjects will be monitored after the procedure, and post-biopsy care 
instructions will be provided to the subjects. 
 
 
Medication Dispensation and Randomization: Subjects eligible for, and willing to 
undergo randomization will be assigned consecutive study numbers.  Investigators, evaluators, 
and participants will be blinded to assignment to drug or placebo. Assignment of each study 
number to placebo or colchicine will be performed by the NIH pharmaceutical development 
section (before 2017) or the NIH Investigational Drug Management Section, with individuals 
randomized in blocks of four, stratified for sex (male vs. female) and race (black vs. non-black).   
Subjects in the Open Label arm will receive purchased brand-name colchicine (Colcrys).  
  
iv. 
Interim safety evaluations 


25 
 
Randomized and open-label participants will be contacted via telephone to evaluate 
medication tolerability after 1 week and then monthly until they return for their final evaluation. 
If a randomized or open-label participant develops any concerning adverse event, the individual 
will be scheduled for an immediate clinic appointment with a trial investigator for further work 
up, as necessary.  Additionally, randomized and open-label participants will have one interim 
safety visit at the NIH Clinical Center with one of the investigators (e.g. JY, AD, SB) for a 
physical examination and blood work (CBC, HbA1c, acute care profile, hepatic profile, lipid 
panel, insulin, uric acid, hsCRP and CK), between 4-8 weeks.  Samples for PBMC analysis and 
inflammatory cytokines will be collected at this visit.  A urine sample will be obtained as 
described previously. The in-person interim safety visit can take the place of one of the safety 
telephone calls. 
 
v. 
Final evaluation 
For randomized and open-label subjects, an interval history and physical exam will be 
performed with weight (in kg), height (in cm), and blood pressure measured as above.  
An exit questionnaire will be performed (See Appendix D).  
Fasting blood for complete blood count (CBC), acute care, mineral, and hepatic profiles, 
PT/PTT, beta HCG (female participants only), and creatine kinase (CK) will be obtained to 
monitor for adverse events and to ensure that the patient remains in good clinical health. 
Additionally, fasting research blood samples, as described in the baseline evaluation for PBMC 
analysis, inflammatory cytokines, endothelial adhesion molecules, lipoproteins, leptin, 
adiponectin, and research specimens to store for future studies, will be obtained.   
Stool sample for future analyses as described previously. 
Urine sample and eight hour urine collection as described previously.  
FSIVGTT: As described previously. 
DXA Scan as described previously. 
CT Abdomen-for liver and intra-abdominal adipose tissue as discussed previously. 
Subcutaneous abdominal adipose tissue biopsy as described previously. 
 
vi. 
Washout evaluation 
For randomized and open-label subjects, an interval history and physical exam will be 
performed, as above.  
Fasting blood as described in the Final Visit.  
Urine sample and eight hour urine collection as described previously.  


26 
 
Stool sample as described previously. 
FSIVGTT as described previously. 
DXA Scan as described previously. 
CT Abdomen-for liver and intra-abdominal adipose tissue as discussed previously. 
Subcutaneous abdominal adipose tissue biopsy as described previously. 
 
E. Biological Specimens 
i. 
Blood Loss 
a. Screening Visit 
i. Acute care, mineral, hepatic panel, CK,  
8 ml 
TSH, Free T4, T3, insulin, hsCRP, IGF1 
ii. CBC/HbA1c 
3 x2 = 6 ml 
iii. ESR 
1 ml 
iv. PT/PTT 
4.5 ml 
v. OGTT 2-hour glucose, GH 
2 x3 x3= 18 ml 
vi. OGTT hsCRP (at 2hr time point) 
1 mL 
vii. Research (Lavender) 
18 ml 
viii. Research (Green) 
10x4 = 40 ml 
ix. Research (Red) 
20 ml 
x. Research (Red/yellow) 
8 ml 
xi. Research (Gut hormones) 
3 ml 
Total 
127.5 ml 
 
b. Baseline Visit 
i. FSIVGTT 
110 ml 
ii. Glucose (Gray) 
1 ml 
iii. CBC/HbA1c 
3 x2 = 6 ml 
iv. ESR 
1 ml 
v. Acute care, lipid panel, insulin, uric acid, CK 
8 ml 
hsCRP, mineral panel, hepatic panel 
 
vi. Research (Lavender) 
10 ml 
vii. Research (Green) 
10x4= 40ml 
viii. Research (Red) 
10x3= 30 ml 
ix. Research (Red/yellow) 
8 ml 


27 
 
x. Research (for Dr. Sack) 
120 ml (optional) 
xi. Research (Gut hormones) 
3 ml 
Total 
217-337 ml 
 
c. Interim Safety visit (randomized and open-label participants) 
i. CBC/HbA1c 
3 ml 
ii. Acute care, lipid and hepatic panels, CK,  
insulin, uric acid, hsCRP 
8 ml 
iii. Research (Red/yellow) 
8 ml 
iv. Research (Red) 
10 ml 
v. Research (Green) 
10 x3 = 30 ml 
Total 
59 ml 
 
d. Final visit (randomized and open-label participants) 
i. FSIVGTT 
110 ml 
ii. Glucose (GYY) 
1 ml 
iii. CBC/HbA1c 
3 x2 = 6 ml 
iv. ESR 
1 ml 
v. PT/PTT 
4.5 ml 
vi. Acute care, mineral, hepatic, lipid panels, 
8 ml 
insulin, uric acid, CK, hsCRP 
 
vii. Research (Lavender) 
10 ml 
viii. Research (Green) 
10x4= 40ml 
ix. Research (Red) 
10x3 = 30 ml 
x. Research (Red/yellow) 
8 ml 
xi. Research (for Dr. Sack) 
120 ml (optional) 
xii. Research (Gut hormones) 
3 ml 
Total 
221.5-341.5 ml 
 
e. Washout Visit (randomized and open-label participants) 
i. FSIVGTT 
110 ml 
ii. Glucose (GYY) 
1 ml 
iii. CBC/HbA1c 
3 x2 = 6 ml 
iv. ESR 
1 ml 


28 
 
v. PT/PTT 
4.5 ml 
vi. Acute care, mineral, hepatic, and lipid panels, 
8 ml 
insulin, uric acid, CK, hsCRP 
 
vii. Research (Lavender) 
10 ml 
viii. Research (Green) 
10x4=40ml 
ix. Research (Red) 
10x3= 30 ml 
x. Research (Red/yellow) 
8 ml 
xi. Research (for Dr. Sack) 
120 ml (optional) 
xii. Research (Gut hormones) 
3 ml 
Total 
221.5-341.5 ml 
 
Note: Some research blood samples will be sent to our collaborators for analysis of lipid, 
inflammatory, and endothelial parameters.  Other research blood samples will be saved 
for storage in a locked -80oC freezer for possible future research, although there are no 
specific additional studies planned at this time. 
 
ii. Adipose tissue biopsy 
a. Baseline visit 
 
 
 
 
 
 
15 g 
b. Final visit (randomized and open-label participants only)  
15 g 
c. Washout visit (randomized and open-label participants only) 
15 g 
 
 
 
Note: A portion of the adipose samples will be snap frozen and stored in a locked -80oC 
freezer for possible future research, although there are no specific additional studies 
planned at this time. 
 
iii. Urinalysis 
a. Screening visit  
 
 
 
 
10 cc 
b. Baseline visit 
 
 
 
 
 
10 cc + 8hr collection 
c. Interim visit (randomized and open-label participants) 
10 cc 
d. Final visit (randomized and open-label participants) 
10 cc + 8hr collection 
e. Washout visit (randomized and open-label participants) 10 cc + 8hr collection 
 
iv. Stool sample 
a. Baseline visit 
 
 
 
 
 
10 cc 


29 
 
b. Final visit (randomized and open-label participants) 
5 cc 
c. Washout visit (randomized and open-label participants) 5 cc 
 
F. Molecular Genetic Analysis of DNA: Yes.  Samples will be collected and stored for potential whole 
exome or whole genome sequencing for alleles linked to obesity, metabolic syndrome, or response to 
colchicine. 
 
G. Approved Drugs:  
No experimental studies involve approved drugs. Insulin is administered during the FSIVGTT. 
Lidocaine is used during adipose tissue biopsies. 
 
H. Unapproved Drugs: Colchicine is FDA-approved for the treatment of gout and Familial 
Mediterranean Fever. It is unapproved for the amelioration of insulin resistance or metabolic 
syndrome.  In this study we plan to use doses approved and previously proven safe for gout 
prophylaxis – 0.6mg PO BID.58,68  From 2014-2016, the NIH Pharmaceutical Development Section 
used colchicine USP compounding powder to make identical-looking colchicine 0.6 mg and placebo 
capsules. After this date, Pine Pharmaceuticals will follow the same procedures to produce 
colchicine and placebo capsules. For the Open Label arm, participants will receive brand-name 
colchicine (Colcrys).  Participants will be instructed to take one capsule twice daily.  If participants 
develop intractable diarrhea, or other mild side effect that does not warrant medication 
discontinuation and/or study termination, the dose may be reduced to one capsule daily (see Section 
V.A.v. and Appendix F).  If side effects resolve, and the subject remains considerably improved or 
symptom-free for two weeks, the dose may be increased back to twice daily at the investigator’s 
discretion.  All subjects will receive a “Medication Guide” (See Appendix E).  An IND has been 
obtained from the FDA (120722). 
 
I. Sharing of Data with Subjects  
 
Specific results that will be given to participants or their health care providers:  If participants have 
concerning results during any of the visits, this will be communicated both to the patient and their 
designated health care providers. At the conclusion of the entire study, when the randomized 
assignment of subjects to medication is given to the Investigators and the analysis of the results is 
complete, the overall results of the investigation will be given to participants and they will be 
informed of the group to which they were randomized.  For the Open Label arm, once all seven 


30 
 
subjects have completed their participation and analysis of the results of the arm has been completed, 
they will be communicated to the participants of the Open Label arm. 
 
J. Questionnaires/Psychological instruments: The Hollingshead Two Factor Index of Socioeconomic 
Status100 will be administered at the Baseline visit. A non-validated exit questionnaire examining the 
patients’ perceptions of their experience in the protocol will be performed at the final visit. 
 
K. Genetic counseling: n/a 
 
L. Follow-up of participants:  After the baseline visit, randomized and open-label participants will be 
contacted by a study investigator by phone at 1 week, 1 month, and 2 months to assess for any 
adverse outcomes and adherence.  If a participant develops any concerning adverse events, the 
individual will be scheduled for an immediate clinic appointment with a trial investigator for further 
evaluation, as necessary.  Additionally, an interim safety visit at the NIH Clinical Center with one of 
the investigators (e.g. JY, AD, SB) and laboratory examination (e.g. CBC, acute care profile, hepatic 
profile, and CK), will be performed for randomized and open-label subjects between 4-8 weeks. 
 
Participants will be contacted by a study investigator in the event that any abnormal laboratory, 
imaging or EKG findings are found during testing at any of the visits.  At the investigator’s clinical 
discretion in conjunction with the subject’s wishes, these abnormalities may be worked up further at 
the NIH Clinical Center as necessary. 
 
M. Conditions for discharge from the protocol (any of the following):  
a. Completion of the protocol.  Specifically, for evaluation-only participants, the subject 
completes the screening visit and baseline visit.  For randomized and open-label 
participants, the subject also completes at least 90 days of investigational medication 
(colchicine or placebo), and the final visit, as described above. 
b. Development of a significant toxicity, such as myositis, agranulocytosis, acute kidney 
injury (see Section V. A. v.), generally defined as grade II or greater toxicity on the 
CTCAE 4.03 list (see Appendix F and attached file for more information).114 
c. Development of an exclusion criterion, besides T2DM or weight change (see Section IV. 
B.) 
d. Voluntary withdrawal from the trial 
e. Non-compliance with the study procedures at baseline assessment (e.g. unwillingness to 
take investigational medication, undergo FSIVGTT, etc.) 


31 
 
 
V. Analysis of the Study/Oversight 
 
 
A. Clinical Description:   
i. Study Administration and Data Collection, Management, and Storage:   
 
The study will be conducted by the research team as listed above.  Samples and data will 
be coded. Human biospecimens will be collected using procedures appropriate for the 
type of biospecimen being collected and will be handled in accordance with the U.S. 
Occupational Safety and Health Administration’s Bloodborne Pathogens Standard for 
Samples. The principal investigator and the co-investigators will have access to 
identifiable participant records. Data will be coded by subject number, but will be 
readily associated with identifiable participant records. Records containing personal 
identifiers will be maintained consistent with the security measures required by the NIH. 
Data will either be transferred directly from the electronic medical record into the 
NICHD Clinical Trials Data Base (CTDB), or for data where direct transfer is 
unavailable, will be double-entered by hand into CTDB.  All data will be kept on secure 
computers in the SGO office, whose doors will be locked when staff is not present.  All 
paper data will also be kept in locked areas in the SGO office. 
Serum and plasma samples not analyzed immediately (as described above) will be stored 
in locked freezers by the NICHD sample management team supervised by the NICHD 
Clinical Director and tracked/managed through CTDB. Human biospecimens in storage 
will have a unique identifier, will be labeled with a printed label and will contain a 
barcode. Samples will be tracked using a computer‐based inventory system that records 
the location and detailed information of every specimen in the repository. 
Sample freezers will be operated using facility environments that include ambient 
temperature controls, good air circulation, lighting, and security. Systems are in place to 
allow for local and remote temperature monitoring of freezers. The NIH has an 
emergency preparedness plan that covers equipment failures and power interruption, 
including back‐up storage capacity and back‐up power generators.  
 
Participants give explicit permission regarding sample use in the consent form of the 
study, indicating if samples may be used for future experimental testing related to 
colchicine response, body weight and metabolism and specify if additional consent is 


32 
 
required.  At the conclusion of the study, samples will be retained for future 
experimental testing related to colchicine response, body weight and metabolism. 
 
The PI will inform the IRB if obtained samples are lost or destroyed before they are 
assayed for primary or secondary outcomes. Loss or destruction of samples saved only 
for tertiary outcomes or future unspecified research will not be routinely reported, unless 
such loss also entails a breach of the Privacy Act. 
 
Data safety monitoring board (DSMB): A data safety and monitoring board will be 
assembled as required by NICHD for pharmaceutical studies. 
 
ii. Publication of Research Findings:   
 
On conclusion of the randomized trial, it is hoped that the results of this pilot 
investigation will be publishable. If so, findings will be submitted to a peer-reviewed 
journal. Regardless of publishability, results will be deposited on www.clinicaltrials.gov 
as required by governmental rules. 
 
iii. Statistical Analysis of the Data 
 
Data analyses will be conducted by the investigators. The primary outcome of the 
randomized study will be change in insulin sensitivity as calculated by the minimal model 
from data obtained through the FSIVGTT in subjects who are randomized to colchicine 
versus those given placebo. Secondary outcomes will be changes in metabolic parameters 
(e.g. AIRg, disposition index, glucose effectiveness, HOMA-IR, HbA1c, lipid panel), and 
the inflammatory marker hsCRP.  Additionally, changes in other inflammatory markers, 
endothelial cell adhesion markers, PBMC inflammatory parameters, SAT adipocyte size, 
SAT inflammatory parameters, and adipose tissue compartments will be evaluated as tertiary 
outcomes.   
 
All analyses will be planned to be performed as intention-to-treat for all randomized 
subjects.  For the primary outcome and the secondary outcomes, we will use an analysis of 
covariance (ANCOVA) to examine the differences between treatment arms, taking into 
account age, baseline body fat percentage, change in body fat percentage, and sex. Two-
sided significance tests will be performed for these analyses, so that both positive and 
negative treatment effects may be detected.  Spearman rank will be used for correlations. 


33 
 
 
For the open-label trial of seven patients with T2DM, the mean change (and the 
standard deviation) for the same variables pre-post treatment will be evaluated to help 
calculate the power of a potential future RCT. 
 
iv. Monitoring Subjects and Criteria for Withdrawal 
 
Screening evaluations may lead to withdrawal of subjects who are not eligible according to 
inclusion/exclusion criteria. Noncompliance with study procedures before subjects are started 
on drug may lead to withdrawal of study participants. Subjects will be followed using an 
“intention to treat” model once randomized.  Phone contacts will be made to review 
medication tolerance and assess for development of serious adverse events after 1 week, 1 
month, and 2 months of treatment. Subjects will be seen if serious adverse events are 
suspected. If subjects are seen by their own physicians for illnesses, we will request the records 
for those visits to determine if they are possibly related to the research. 
 
v. Stopping Rules: 
 
Events that will result in discontinuation of treatment include: pregnancy or serious 
unanticipated complications, including development of any medical problem listed in the 
exclusion criteria after starting on drug. Subjects will be excluded if they have any verified 
abnormality in laboratory values or physical status that cannot be explained by a mild 
intercurrent illness (or by obesity and insulin resistance itself) that in general are considered  
CTCAE grade 2 (See Appendix F) or greater for gastrointestinal, hematologic, clinical 
hemorrhage, kidney/bladder, alopecia, pulmonary, cardiac, neurocerebellar, allergy, flu-like 
symptoms, metabolic, or eye toxicities; and grade 3 or greater for infection, anorexia, 
circulatory, neurologic, dermatologic, coagulation, endocrine, or performance status 
toxicities.115  Problem-specific stopping rules have been defined in the CTCAE v4.03 
submitted to the IRB in conjunction with this protocol.  Investigator error leading to initiation 
of treatment in an ineligible subject will lead to treatment discontinuation as soon as the error 
is uncovered. Should discontinuation be required for any reason, no tapering of colchicine is 
necessary; subjects will be requested to return all unused medication.  Because the randomized 
study is a pilot intended to identify the sample size needed for a fully-powered trial, there are 
no formal stopping rules that would halt the study before all participants have been 
randomized. 


34 
 
 
B. Molecular Studies 
 
Samples will be stored for future genetic studies of variants associated with body weight and 
inflammation. Examples of genes that may be examined include obesity-associated genes such 
as leptin, leptin receptor, melanocortin 4 receptor, melanocortin 3 receptor, brain-derived 
neurotrophic factor, the beta 3 adrenergic receptor, and SIM1, as well as inflammatory genes 
such as NLRP3, ASC, procaspase-1, IL-1, and IL-6. The consent form has been prepared to 
allow participants agree to whole-exome/genome sequencing for identification of genetic 
changes linked to inflammation, obesity or obesity-linked dysregulation of metabolism. 
 
In some instances, investigators will share coded specimens from this protocol with 
collaborators who will not be provided with a key to the code.  Subcutaneous adipose biopsy 
specimens will be sent to Dr. Vincent Manganiello’s lab in a de-identified manner, where they 
will be examined for local inflammation.  Dr. Joshua Zimmerberg’s lab will receive coded 
samples for analysis of inflammation and metabolic function, such as adipose GLUT4 mobility.   
 
In collaboration with the Center for Human Immunology, Autoimmunity, and 
Inflammation (CHI) at the NIH, coded samples will be sent for PBMC analysis, including 
mRNA expression array analysis, flow cytometry and cryopreservation.  Samples of PBMC for 
protein lysates will be analyzed by Dr. Vincent Manganiello’s lab via Western Blot analysis to 
examine colchicine’s effects on NLPR3 inflammasome assembly, as well as for its effects on 
inflammasome-mediated IL-1B production.   Dr. Michael Sack, NHLBI, will also receive coded 
serum samples for analysis of PBMC inflammation. 
 
Dr. James Goedert (NCI) will receive coded samples of blood for analysis of estrogen 
and androgen markers, as they may change with changes in insulin sensitivity. For collaborators 
outside the NIH, The PI will establish these collaborations through an OHSRP request for 
determination and provide a list of all collaborations established in this manner to the IRB at the 
time of CR. 
 
Stool samples will be obtained for future analyses to be performed by CHI. 
 
Dr. Perry Blackshear, NIEHS, will received coded samples of blood and adipose tissue 
for analysis. 
 
VI. Determination of Sample Size:  
 


35 
 
 
The randomized trial is a pilot study, intended to determine the treatment effect size and standard 
deviation for colchicine’s effects on change in insulin sensitivity, to allow for adequate powering of a larger 
future study.  Nonetheless, we will power it so it might be able to detect a moderate-to-large difference 
between treatment groups.  Based on the data of prior studies,116,117 the standard deviation (SD) for change in 
insulin sensitivity as measured by FSIVGTT is about 2 mIU/L/min.  If a similar SD is found in the present 
study, we estimate that a total sample size of 40 subjects (20 colchicine and 20 placebo) is necessary to have 
80% power (β) to detect a 60% difference in insulin sensitivity between colchicine and placebo groups, at 
level of significance <0.05 (2-sided). 
  
VII. Human Subjects Protection: 
A. Rationale for Subject Selection:  This study seeks to understand how colchicine affects insulin 
sensitivity, pancreatic beta-cell function, and low-grade inflammation in humans.  Because obese 
participants have a greater level of insulin resistance than non-obese individuals, and participants 
with MetS have a greater level of inflammation than those without, we selected to test obese 
individuals with metabolic syndrome who demonstrate both high insulin resistance and evidence 
for inflammation.  Participants with type 2 diabetes mellitus frequently are taking medications 
that may confound the results of the tests we plan to study.  Additionally, diabetics are presumed 
to have beta-cell destruction which may be too far advanced to demonstrate benefit from an 
intervention, whereas a disease process in an earlier stage (e.g. insulin resistance and/or 
prediabetes) may demonstrate benefit. On the other hand, diabetics also have the greatest level of 
obesity-associated inflammation, so they may demonstrate benefit from colchicine.  To 
investigate this further, we will recruit seven subjects with diet-controlled DM to an Open Label 
arm.    
In order to expand our knowledge of local insulin action at the level of the adipocyte, we 
also plan to enroll subjects across a larger spectrum of insulin sensitivity/resistance for testing 
only at the Screen and Baseline Visits.  Subjects who are not eligible to be randomized to study 
drug but who will be enrolled to the Evaluation Only arm will include those who are not obese, 
obese but without significant insulin-resistance or evidence of inflammation, and those with diet-
controlled type 2 diabetes. Such subjects are excluded, as listed above, only if they are pregnant 
or nursing, use medications or substances that affect the validity of measures, have a significant 
medical/psychiatric condition, or weigh too much for required procedures. 
Children are not studied because the nature of the experiment involves a minor increment 
above minimal risk (adipose tissue biopsies, potentially toxic medication), that can be answered 
in adult subjects.   


36 
 
Adults of all races and ethnicities will be included. Since metabolic syndrome is identified in 
large percentages among minority groups including Asian Americans, African American and 
Hispanic Americans, we anticipate good representation of all major races/ethnicities. It is 
expected, given our recruitment procedures targeting individuals living in the greater 
metropolitan Washington D.C. area, that we will recruit rates of minority participation in excess 
of their representation in the Washington, D.C. metropolitan area: 64.2% Caucasian, 27.2% 
African-American and 8.6% Hispanic. 
B. Participation of Children and Other Vulnerable Populations: n/a 
C. Screening Methodology 
Subjects who appear eligible when assessed during a phone screening intended to assess general 
health and body weight/height (to determine BMI) will attend a screening visit at the NIH 
Clinical Center, during which time eligibility will be determined. History and physical 
examination will be conducted by a licensed practitioner. Laboratory data from blood draw and 
pregnancy testing will be reviewed before subjects are scheduled for the Baseline visit and 
randomization to drug/placebo (or initiation of colchicine in the open-label arm).  
 
Information regarding the key assays used for eligibility criteria (all measured by the NIH 
Clinical Center Laboratory Medicine Department): 
 
Glucose 
 @75mg/dL    
: intraassay CV 2%             interassay CV 3% 
 @ 379 mg/dL  
: intraassay CV 1%             interassay CV 2% 
Sensitivity: 1 mg/dL 
 
  
Insulin 
@ 24.2 µU/mL    
: intraassay CV 1.2% 
 
interassay CV 6.0% 
@ 82 µU/mL  
: intraassay CV 1.0% 
 
interassay CV 2.5% 
Sensitivity: 0.2uU/mL 
  
hsCRP 
@ 0.239 mg/dL     : intraassay CV 5.2%              
interassay   5.2% 
@ 0.650 mg/dL    
: intraassay CV 5.0%             
interassay   5.7% 
Sensitivity: 0.016 mg/dL 


37 
 
  
Triglycerides 
@ 68 mg/dL     
: intraassay CV 3%            
interassay CV 4% 
@384 mg/dL    
: intraassay CV 2%            
interassay CV 2% 
Sensitivity: 2 mg/dL 
  
HDL cholesterol 
@ 26 mg/dL    
: intraassay CV 2.3%            
interassay CV 2.7%   
@ 47 mg/dL    
: intraassay CV 1.6%            
interassay CV 2.3%   
@ 67 mg /dL   
: intraassay CV 1.9%           
interassay CV 2.1% 
Sensitivity: 3 mg/dL 
 
Hemoglobin A1c 
@ 5.1% 
 
: intraassay CV 0.4% 
 
interassay 1.11% 
@9.9% 
 
: intraassay CV 0.5% 
 
interassay 0.73% 
Sensitivity: 4.2% 
 
D. Risks/Benefits Analysis (including considerations of alternatives to participation) 
1. Potential Benefits, in addition to have the results of all screening testing, (as outlined above) 
from randomization include the following 
a. Improving insulin sensitivity 
b. Improving pancreatic beta-cell reserve 
c. Decreasing inflammation 
d. Decreasing cardiovascular risk 
e. Benefit to medicine and society 
2. Risks/Discomforts 
a.    Colchicine (randomized and open-label participants only) 
i. Adverse Reactions 
Among post-marketing experience in the use of Colcrys (the trade name for 
colchicine that is available in the US), adverse reactions have been generally 
reversible upon temporarily interrupting treatment or lowering the dose of 
colchicine. The following adverse reactions have been reported with colchicine: 
- 
Neurological: sensory motor neuropathy 
- 
Dermatological: alopecia, maculopapular rash, purpura, rash 


38 
 
- 
Digestive: abdominal cramping, abdominal pain, diarrhea, lactose intolerance, 
nausea, vomiting 
- 
Hematological: leukopenia, granulocytopenia, thrombocytopenia, 
pancytopenia, aplastic anemia 
- 
Hepatobiliary: elevated AST, elevated ALT 
- 
Musculoskeletal: myopathy, elevated CPK, myotonia, muscle weakness, 
muscle pain, rhabdomyolysis 
- 
Reproductive: azoospermia, oligospermia  
Tolerance, abuse, or dependence with colchicine has not been reported.68 
 
In recent clinical trials, the most commonly reported adverse reactions were 
abdominal symptoms such as diarrhea, cramping, nausea, diarrhea, abdominal pain, 
and vomiting. For example, in a randomized, placebo-controlled trial investigating 
colchicine 0.6mg PO bid for 6 months in participants after coronary angioplasty, of 
the 130 subjects in the intervention group 28% developed diarrhea, whereas other 
side effects, including nausea or rash, were not significantly different from 
placebo.118  Another randomized placebo-controlled study investigating colchicine 
0.5mg PO bid for 6 months in DM participants undergoing  percutaneous coronary 
intervention (PCI) with a bare metal stent (BMS), of the 196 subjects 16% 
developed diarrhea or nausea in the colchicine group vs. 7% in the placebo group.81 
 
Subjects who may develop renal or hepatic impairment due to causes independent of 
participating in the protocol are at increased risk for developing adverse reactions 
and toxicities as colchicine is metabolized in the liver, and excreted in significant 
amounts in the bile and urine. (See Section VII. H.) 
 
ii. Fatal Overdose 
Fatal overdoses, both accidental and intentional, have been reported in adults and 
children who have ingested colchicine. The exact dose of colchicine that produces 
significant toxicity is unknown. Fatalities have occurred after ingestion of a dose as 
low as 7 mg over a 4-day period, while other participants have survived after 
ingesting more than 60 mg. A review of 150 participants who overdosed on 
colchicine found that those who ingested less than 0.5 mg/kg survived and tended to 
have milder toxicities, such as gastrointestinal symptoms, whereas those who took 


39 
 
0.5 to 0.8 mg/kg had more severe reactions, such as myelosuppression. There was 
100% mortality in those who ingested more than 0.8 mg/kg.  
 
The first stage of acute colchicine toxicity typically begins within 24 hours of 
ingestion and includes gastrointestinal symptoms, such as abdominal pain, nausea, 
vomiting, diarrhea, and significant fluid loss, leading to volume depletion. 
Peripheral leukocytosis may also be seen. Life-threatening complications typically 
occur 24 to 72 hours after drug administration, and death may result from respiratory 
depression and cardiovascular collapse. Individuals who survive a severe overdose 
may develop rebound leukocytosis and alopecia one week after the initial ingestion. 
Treatment of colchicine poisoning should begin with gastric lavage and supportive 
measures. No specific antidote is known, and colchicine is not effectively removed 
by dialysis. 
 
 
 
 
iii. Drug Interactions 
Colchicine is metabolized by P-gp and CYP3A4. Life-threatening and fatal drug 
interactions have been reported in individuals taking colchicine concurrently with P-
gp and/or strong CYP3A4 inhibitors (see Appendix B1). If treatment with a P-gp or 
strong CYP3A4 inhibitor is required in a subject, the investigational medication will 
be discontinued and the patient will be withdrawn from the protocol.  
 
iv. Pregnancy 
Adequate well-controlled studies on the use of colchicine in pregnancy do not exist.  
Among published reports of pregnant women using colchicine to control their 
Familial Mediterranean Fever, no increased risk of miscarriage, stillbirth, or 
teratogenic effects was seen.  However, colchicine did demonstrate fetal toxicity and 
teratogenicity in the offspring of pregnant rats.  Subjects currently pregnant, 
breastfeeding, or planning to become pregnant will be excluded from the study.  
Enrolled female subjects will be strongly advised to use contraception and condoms 
if sexually active. As noted above, women who become pregnant while taking study 
medication will be immediately told to stop medication and will be withdrawn from 
all study procedures. The study team will follow up with the participant regarding 
the outcome of the pregnancy.  
 


40 
 
b. Physical Examination by a health care provider involves no known risk, but does take 
time. A limited physical examination will be performed in a concise but thorough 
manner with appropriate measures taken to provide the privacy of the subject. 
c. Questionnaires are also without significant risk, but are inconvenient because of the 
time required to complete. 
d. DXA scanning is not painful, but may be inconvenient because of the time needed to 
complete the study. DXA scanning involves radiation exposure for research purposes 
only.  According to the manufacturer’s specifications, DXA scanning for body 
composition using the array beam delivers an effective dose of 0.00003rem total body 
radiation. This calculated value is known as the “effective dose” and is used to relate the 
dose received by each organ to a single value. This amount of radiation from the three 
DXA scans to be performed in this study is 0.00009 rem. For comparison, the average 
person in the U.S. receives a radiation exposure of 0.3 rem/yr from natural background 
sources, such as from the sun, outer space, and from radioactive materials that are found 
naturally in the earth’s air and soil.  
e. Blood withdrawals will remain well within the NIH guideline for adults of 7 ml/kg 
every 6 weeks. Blood collection with venipuncture is associated with mild discomfort 
and the possibility of localized bruising or extravasations. The risk of infection, 
phlebitis, or fainting is extremely small. 
f. Stool samples are also without significant risk, but some subjects may find them 
uncomfortable to collect.  The surveys and food records are without significant risk, but 
may be inconvenient because of the time required to complete. 
g. Oral glucose tolerance test is also is without significant risk, but is inconvenient 
because of the time required to complete the study. The only risks from this kind of 
study are those described for any blood draw, as well as developing nausea from the oral 
glucose.  As we are screening out patients with diabetes mellitus, the risk of developing 
hyperglycemia exists, but in most cases should be transient and not clinically significant. 
h. Subcutaneous abdominal adipose tissue biopsies. The risks associated with biopsies 
include pain, bleeding, bruising, infection, numbness related to nerve injury, and 
scarring or keloid formation. Lidocaine will be used to diminish pain. A sterile approach 
will be incorporated to avoid risk of infection, and to our knowledge, there has not yet 
been a report of infection. After the procedure, sterile dressing will be applied, in 
addition to an ice pack; the latter will be used to decrease bleeding/hematoma formation. 
In the immediate post-procedure period (while subjects are observed), the site will be 


41 
 
monitored for immediate complications, and addressed appropriately. Biopsies from 
abdominal subcutaneous fat will be taken. Subjects will also be instructed on signs of 
these risks and to observe the site after discharge, and to immediately report any 
concerns to the clinical team. The physician/nurse practitioner who is in charge of 
performing the biopsy will fill out a "Surgical/Invasive Procedure Verification 
Checklist” during the procedure to make sure every prerequisite to ensure safety of the 
subject is met. If increased occurrences of any of these risks are noted, technique will be 
adjusted in attempt to reduce the risk. 
i. 
Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) is 
inconvenient because of the time it takes to complete, the need for two intravenous lines, 
and the need to be confined to bed.  The only risks from this kind of study are those 
described for any blood draw (see #5), mild arm tenderness while the dextrose is 
infused, and the possibility of a decreased blood glucose value from the administration 
of insulin. The standard dose of insulin administered for evaluation of growth hormone 
secretory capacity, 0.05 U/Kg, will be administered.  With mildly low blood sugars (< 
50 mg/dL), subjects get hungry and may become drowsy or sweaty.  With blood sugars 
under 30 mg/dL, subjects may be difficult to arouse or have seizures.  However, because 
the obese adults to be studied on this protocol will all have some degree of insulin 
resistance, significant hypoglycemia is not anticipated.  Nevertheless, a physician or 
nurse practitioner will be present during this test for the first hour of the test (including 
the first thirty minutes following insulin administration) to monitor for signs of 
significant hypoglycemia. The principal investigator will be notified immediately of any 
glucose measurement less than 40 mg/dL. The principal investigator will use his clinical 
judgment in developing an appropriate, situation-specific management plan.  Treatment 
will take place as needed with dextrose or glucagon according to clinical evaluation. 
j. 
CT Abdomen for hepatic and intra-abdominal adipose tissue is not painful, but may 
be inconvenient because of the time needed to complete the study.  Some people feel 
anxious while inside the CT scanner. 
 
Computed tomography involves radiation exposure for research purposes only.  
Although each organ will receive a different dose, the amount of radiation exposure 
subjects will receive per scan is equal to a uniform whole-body exposure of 0.031 rem. 
This calculated value is known as the “effective dose” and is used to relate the dose 
received by each organ to a single value. The total effective radiation dose that patients 
will be exposed to in the study is 0.093 rem, well within the dose guideline established 


42 
 
by the NIH Radiation Safety Committee for adult research subjects. The guideline is an 
effective dose of less than 5 rem/yr.  No contrast dye will be administered as part of this 
protocol. 
 
One possible effect that could occur at these doses is a slight increase in the risk of 
cancer. The natural chance of a person getting a fatal cancer during his/her lifetime is 
about 25 %. The increase in the chance of getting a fatal cancer as a result of the 
radiation exposure received from this research study is 0.1%. Therefore, the total risk of 
fatal cancer may be estimated to increase from 25% to 25.1%. This change in risk is 
small and cannot be measured directly. Compared with other everyday risks, such as 
flying in an airplane or driving a car, this increase is considered slight. 
 
Subjects will be advised to notify the research staff if they have participated in 
research studies at the NIH or other institutions that involved the use of radiation so as to 
make sure that the total radiation dose from all studies is not excessive. Women with 
childbearing potential must have a negative pregnancy test before undergoing the CT 
scan. 
k. “Smart” Pill Bottle Cap.   We will use  a “MEMS cap” (MWV Switzerland, Ltd) on 
the top of the medicine bottles to record patient adherence to the study drug. As 
described above, the cap records the date and time that the bottle is opened, and the data 
will be downloaded by one of the protocol investigators onto a laboratory computer.  
This will pose no additional risk to the subjects.    
 
l. 
Testing for DNA including exome/whole genome sequencing. The risks from DNA 
tests are primarily the risk of discovery of incidental medical information, risks of 
genetic discrimination and risks related to confidentiality and data availability.  
a. 
Incidental medical information.  Genetic risk factors may be found for 
diseases unrelated to the condition for which the patient is being studied. This risk is 
inherent in any genetic analysis; however, the risk increases with increased 
magnitude of data and degree of analysis.  This study will uncover incidental 
information. In some cases this information will provide additional details about 
diseases already known to be present in a family. For example, identification of a 
BRCA1 mutation may be new information for a family, but they may already know 
that breast cancer occurs in their family. Similarly, identification of a Huntington 
disease mutation is not likely to occur in a family without any prior family history. 
Clinically significant information could be identified for diseases that were not 


43 
 
previously recognized to be a concern in a given family.  This could occur with 
dominant disorders that show decreased penetrance or with recessive genetic 
disorders. Exome studies can detect carrier status for recessive disorders such as 
cystic fibrosis or sickle cell anemia.  Determination of carrier status for recessive 
disorders will not impact the subject’s health directly, but this information does have 
potential reproductive implications for the subject and other members of the family. 
This information could cause anxiety in some individuals; however, being aware of 
these conditions provides an opportunity for genetic counseling. 
As genetic understanding of genetic risk factors for multifactorial disorders 
increases, we may detect vast numbers of polymorphisms that slightly increase the risk 
of a specific disorder such as diabetes or heart disease.  The knowledge of these risk 
factors could provide an opportunity to alter lifestyle factors that contribute to the risk, 
but at the same time could produce anxiety.  Unless felt to be of urgent medical 
importance, we will not report these results to patients or families.  General principles 
guiding a decision to inform guardians about genetic information obtained from this 
study will be: 
i. The genetic change must be known or predicted to be of urgent clinical 
significance to either a proband or a first degree relative. 
ii. Knowledge of the finding must have a clear direct benefit that would be lost if 
diagnosis was made at a later time point.  Specifically, knowledge of this risk 
factor will substantially alter the patient’s medical care.   
iii. The potential benefit of knowing a genetic disorder exists clearly outweighs the 
potential risks of anxiety and subsequent medical testing that could result from 
this knowledge. 
iv. Autosomal recessive mutations will only be reported if a) the carrier frequency 
for mutations in that specific gene is greater than 1% (This corresponds to 
disorders with a disease incidence of more than 1/40,000), b) the syndrome results 
in significant morbidity, c) early diagnosis and intervention would have 
significant benefit for an affected individual, and d) early diagnosis is not likely 
to be made by other means.   
 
The decision to notify or not notify will be made by the study investigators based on the 
state of genetic knowledge at the time of data analysis.  Although not precluded, the 
database will not be actively screened for changes that in the future are found to be 


44 
 
associated with a specific disease.  If a genetic change of clinical significance is 
detected, subjects will be given the option to have confirmatory testing performed in a 
CLIA approved laboratory.  Confirmatory testing will be performed on new DNA 
samples obtained from the probands.  Identification of genetic disease in a proband 
could produce anxiety for the parent, siblings or other relatives.  Relatives of the proband 
could learn that they are at risk for a genetic disorder. 
 
b. Genetic Discrimination:  If an individual elects to have a genetic finding 
confirmed, that information will then become part of the medical record at the NIH.  
This information will be released to third parties if the individual sign a release of 
information form.  An insurance company or an employer could interpret this to be a 
pre-existing condition to deny benefits or coverage.   This however, is largely a 
theoretical concern.  No cases of discrimination are known to have resulted due to 
participation in a research study. The risk of genetic discrimination in the context of 
health insurance and employment should also be decreased by Genetic Information 
Nondiscrimination Act of 2008. 
c. Confidentiality and Data availability:  Samples and data will be coded.  Only 
individuals involved in consenting and patient care will have access to identifiers.  
Records containing personal identifiers will be maintained consistent with the security 
measures required by the NIH. We will follow guidelines developed by the NIH for 
projects funded by the Federal Government.  In lieu of specific guidelines, subjects 
may opt out of having sequence data deposited in public databases.  
 
Results of genetic tests performed for research will not be placed in the medical record.  
It is possible that we will send subject’s DNA to other scientists working with us on 
obesity gene studies, but in this case personal identifiers will be removed. If a subject 
chooses to withdraw from the study, we will keep the DNA for analysis, unless the 
subject requests that the sample be destroyed. 
 
3. Assessment of Risk/Benefit Ratio:  Although it is impossible to quantify the exact risk to 
benefit ratio, we feel that the risks as mentioned above are a minor increment above minimal 
risk and mitigated whenever possible.  The potential benefit to the randomized and open-
label subjects can be large with a decrease in cardiovascular risk factors, improvement in 
metabolic profile, and decrease in chronic inflammation.  Additionally, we feel that this 


45 
 
study will contribute significant knowledge to the field of medicine in examining a novel 
therapeutic approach in humans to improve insulin resistance and metabolic syndrome.  To 
date the effects of disrupting the NLRP3 inflammasome on metabolic parameters and 
glucose homeostasis have not been studied in humans with metabolic syndrome. 
 
4. Alternatives to participation:  The major alternative is not to participate in this experiment, 
as there are no inflammasome-reducing medications approved for patients with metabolic 
syndrome. Participants could also consider starting a formal lifestyle modification program, 
including improved diet and exercise.  Established medical options for obesity and metabolic 
syndrome include undergoing bariatric surgery or starting weight-loss medications (e.g. 
lorcaserin or phentermine/topiramate).  Participants can look up research alternatives for 
interventions for obesity or metabolic syndrome on www.clinicaltrials.gov.     
 
E. Privacy and Confidentiality Provisions 
We will follow all relevant NIH policies and HRPP SOPs. Samples and data will be coded.  
Only individuals involved in consenting and patient care will have access to identifiers.  Records 
containing personal identifiers will be maintained consistent with the security measures required 
by the NIH. Access to the code will be limited to the study investigators (e.g. JY, AD, TC, and 
SB).  Electronic data will be password protected and accessible only by authorized study 
personnel. Electronic data will be backed up daily and stored at a secure server. All hardcopy 
data will be locked in Dr. Yanovski’s storage cabinets in research offices at the NIH Clinical 
Research Center and will be accessible only by authorized study personnel. All data will be 
collected specifically for the purpose of the current proposed research project. Any email 
communications that involve PII will be sent using encryption or the secure email system of the 
NIH. Since even when precautions are taken to ensure participant confidentiality, data collection 
in any study is accompanied by threat to privacy and confidentiality, in the unlikely event of a 
potential breach of confidentiality, the PI will immediately inform the IRB. The hsCRP and other 
clinical chemistry results are done by NIH Clinical Pathology and will be in the medical record. 
Results of the serum cytokine profile, endothelial adhesion profile, lipoprotein NMR, DXA, 
DNA, and adipose tissue studies will not be placed in the medical record.   
 
In the Clinical Trials Database, clinical and demographic information will include age; sex; 
race/ethnicity; family history of diabetes, hypertension, or hyperlipidemia and results entered 
from each case report form for visits and phone conversations. 


46 
 
 
F. Compensation 
We will use NIH guidelines for payment of research volunteer. The remuneration is based on 
time and inconvenience during the stay. Payment will be as follows: 
 
[For randomized or open-label subjects] 
1. Outpatient screening visit: 
$100 
2. Baseline evaluation visit: 
$300 
3. Interim Safety Visit: 
$50 
4. Final Visit: 
$300 
5. Washout Visit: 
$300 
       Total= 
$1050 
 
[For evaluation-only subjects] 
1. Outpatient screening visit: 
$100 
2. Baseline evaluation visit: 
$300 
 
Total= 
$400 
 
 
G. Consent Procedures 
Each subject will receive a written explanation of the purposes, procedures, and potential 
hazards of the study (See Consent Form). The purpose of the project, all testing procedures, and 
study components will be described in detail. Potential participants will also be informed of the 
possible risks and inconveniences of the study. Consent will be obtained only by the principal 
and associate investigators and Key Research Personnel designated on the first page of the 
protocol (e.g. JY, AD, SB), in person at the beginning of the first Screening Visit.  
Communication of this information and of the subject’s consent will be documented in the 
medical record. All subjects will be informed of their right to withdraw from the study at any 
point of time during the study. 
 
Non-English–Speaking Participants 
If a non-English speaking participant is unexpectedly eligible for enrollment, the participant 
will be provided with the CC Short Written Consent Form for Non-English Speaking Research 
Participants in the participant’s native language and a verbal explanation of the purpose, 


47 
 
procedures and risks of the study as described in MAS Policy M77-2, NIH HRPP SOP 12 and 
45 CFR 46.117(b)(2). The IRB-approved English consent form will serve as basis for the verbal 
explanation of the study. The investigator will obtain an interpreter unless the investigator is 
fluent in the prospective participant’s language. Preferably, the interpreter will be someone who 
is independent of the participant (i.e., not a family member). Interpreters provided by the CC 
will be used whenever possible. The interpreters will interpret all oral communications (English 
to target language and conversely) about the IRB-approved English consent form, facilitate 
discussion between the participant and investigator, and ensure understanding. 
The IRB-approved English consent form will be signed by the investigator obtaining consent 
and a witness to the oral presentation. The CC Short Written Consent Form will be signed by 
the participant and a witness who observed the presentation of information. The interpreter may 
sign the consent document as the witness and, in this case, will note “Interpreter” under the 
signature line. A copy of both signed forms will be provided to the participant to take home. 
The investigator obtaining consent will document the consent process in the participant’s 
medical record, including the name of the interpreter.  
 
We request prospective IRB approval of the use of the short form for up to a maximum of 5 
separate encounters in a given language and will notify the IRB at the time of continuing review 
of the frequency of the use of the Short Form. Should we reach the threshold of 5, we will 
notify the IRB of the need for an additional use of the Short Form and that we will have that 
consent document translated into the given inherent language. 
 
H. Pharmaceutical Information 
Colchicine is an alkaloid chemically described as (S)N- (5,6,7,9-tetrahydro- 1,2,3,10-
tetramethoxy-9-oxobenzo [alpha] heptalen-7-yl) acetamide with a molecular formula of 
C22H25NO6 and a molecular weight of 399.4. 
 
Pharmacokinetics 
Absorption: “In healthy adults, colchicine is absorbed when given orally, reaching a mean Cmax 
of 2.5 ng/mL (range 1.1 to 4.4 ng/mL) in 1 to 2 hours (range 0.5 to 3 hours) after a single dose of 
0.6 mg administered under fasting conditions.  After 10 days on a regimen of 0.6 mg twice daily, 
peak concentrations are 3.1 to 3.6 ng/mL (range 1.6 to 6.0 ng/mL), occurring 1.3 to 1.4 hours 
post-dose (range 0.5 to 3.0 hours). In some subjects, secondary colchicine peaks are seen, 
occurring between 3 and 36 hours post-dose and ranging from 39% to 155% of the height of the 


48 
 
initial peak. These observations are attributed to intestinal secretion and reabsorption and/or 
biliary recirculation.  Absolute bioavailability is reported to be approximately 45%. 
Administration with food has no effect on the rate of absorption, but does decrease the extent of 
colchicine by approximately 15%, which is likely clinically insignificant.”68  
 
Distribution 
“The mean apparent volume of distribution in healthy young volunteers was approximately 5 to 
8 L/kg. Colchicine binding to serum protein is low, 39 ± 5%, primarily to albumin regardless of 
concentration”68.  Accumulation into neutrophils and macrophages is slow, only reaching peak 
concentration at 48 hours.119  
 
Colchicine crosses the placenta (plasma levels in the fetus are reported to be approximately 15% 
of the maternal concentration). Colchicine also distributes into breast milk at concentrations 
similar to those found in the maternal serum.68 
 
Metabolism 
Colchicine is demethylated to two primary metabolites, 2-O-demethylcolchicine and 3-O-
demethylcolchicine (2- and 3-DMC, respectively), and one minor metabolite, 10-O-
demethylcolchicine (also known as colchiceine), primarily through CYP3A4. Plasma levels of 
these metabolites are minimal.68 
 
Elimination/Excretion 
“In healthy volunteers (n=12) 40 – 65% of 1 mg orally administered colchicine was recovered 
unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a 
role in colchicine elimination. Following multiple oral doses (0.6 mg twice daily), the mean 
elimination half-lives in young healthy volunteers (mean age 25 to 28 years of age) is 26.6 to 
31.2 hours.”68 
 
Preparation of Investigational Colchicine by Pharmaceutical Development Section or Pine 
Pharmaceuticals 
Colchicine USP powder, purchased from Spectrum Chemical, will be dispensed. Each capsule 
will contain 600 micrograms of colchicine. Matching placebo capsule will be produced that only 
contain the non-colchicine ingredients. Colchicine will be verified to be chemically pure and to 


49 
 
have acceptable stability using standard approaches by the NIH Pharmaceutical Development 
Section (before 2017), the NIH IDMS subsequently, or Pine Pharmaceuticals. 
 
I. Recruitment Strategies 
Participants will be recruited from Washington, DC and local suburbs in Maryland and Virginia. 
Recruitment efforts will aim to enroll subjects in proportion to their representation in the 
population of Maryland. Subjects of all racial, ethnic and socio-economic backgrounds will be 
invited to participate in this study.  We will contact by mail or email, adult obese subjects who 
have previously indicated interest in research and/or have already participated in protocols run 
by the Section on Growth and Obesity (SGO), to inform them of this new study and assess their 
potential interest.  These potential subjects will be provided with a telephone number and email 
address to call or write if they are interested to request more information. Participants will be 
also be recruited by means of flyers posted in the NIH Clinical Center, in other buildings at the 
NIH campus in Bethesda, MD, and in surrounding local businesses.  If necessary, further 
subjects will be recruited through newspaper advertisements or letter mailings. Advertisements 
will be submitted to the IRB before use. 
 
J. Existing data: n/a 
 
K. Description of criteria for withdrawal from study 
 
 
The types, frequency, and duration of tests and visits are outlined on the flow diagrams 
(Appendix A1-6).  Subjects will be examined at each of their visits. If unanticipated reactions are 
uncovered during the study, we will report these promptly to the IRB. The CRC has ample medical 
resources should any unanticipated event occur. Additionally, study staff will seek evidence of 
emotional or physical distress or discomfort, and will be instructed to terminate the protocol if a 
participant demonstrates distress. 
 
Study staff will emphasize to participants that they are able to withdraw from the study at 
any time, without penalty. Noncompliance with study procedures may lead to withdrawal of 
study subjects – for example, unwillingness to take the medication or inability to complete 
required testing (e.g. FSIVGTT). Other events that will result in discontinuation of treatment 
include:  
1.  Pregnancy. 


50 
 
2.  Any verified abnormalities in laboratory values or physical status that cannot be explained 
by an intercurrent unrelated illness (or by obesity itself) that are considered CTCAE grade 2 or 
greater for gastrointestinal, hematologic, clinical hemorrhage, kidney/bladder, alopecia, 
pulmonary, cardiac, neurocerebellar, allergy, flu-like symptoms, metabolic, or eye toxicities; and 
grade 3 or greater for infection, anorexia, circulatory, neurologic, dermatologic, coagulation, 
endocrine, or performance status toxicities.115  Problem-specific stopping rules have been 
defined in the CTCAE v4.03 submitted to the IRB in conjunction with this protocol.   
 
Unblinding Procedure 
In the randomized portion of the trial, all participants, Study Site staff, and pathology 
and laboratory personnel are blinded to the individual assignment of the order in which 
colchicine and placebo are administered. Participants will learn their individual assignments (i.e., 
be unblinded) when the trial is complete. In rare instances, it may be necessary to unblind a 
participant's order of assignment before completion of the trial, to a physician, to the Study Site, 
or to the participant.  
In general, however, participants should not be unblinded. Anytime a staff member 
learns the treatment assignment of a participant, the staff member is at risk of being influenced 
by that information. For example, if the unblinded participant was known to have taken the 
active agent and reported a toxicity, the staff member might make inferences about the effects of 
colchicine on that participant, and possibly on other participants as well. The management of 
future participants may be influenced by this information. Maintaining the double-blind design 
offers the best protection against this potential bias. 
In the unlikely event that a Serious and Unexpected Suspected Adverse Reaction 
(SUSAR) occurs and a physician must be unblinded to the treatment group to which an affected 
trial subject belongs, the Investigational Drug Management Section (IDMS) will be contacted by 
a study investigator (usually by the Principal Investigator). The study investigator will request 
that IDMS release the needed information and specify the individual to receive the information. 
IDMS will normally supply unblinding information only to a physician who is not a co-
investigator on the study and make clear that group assignment must not be given to study 
investigators. This procedure is intended to ensure that the identity of the investigational 
medicinal product is revealed only insofar as is necessary. As much as possible, the blinding 
should be maintained for the investigators and for anyone responsible for data analysis or 
interpretation. A subject’s treatment group should not be revealed to a study investigator except 
in a medical emergency, i.e. when this appears necessary to ensure the subject’s safety and 


51 
 
would be instrumental in further treatment decisions. If a subject’s treatment is unblinded, this 
must be documented by IDMS in their written records. In all cases, the reasons and rationale for 
unblinding will be also documented in writing and maintained in the study file. 
Unblinded data are also available to the Data Safety Monitoring Committee (DSMC). In 
the case of a SUSAR, the DSMC is informed and will thus have the opportunity to review 
subject-level data and make any changes to the experimental plan that are required. In the case of 
a SUSAR, the DSMC may elect to reveal the treatment group to which a subject belongs, request 
additional safeguards, or stop the study. The DSMC will assist investigators in deciding if a 
SUSAR requires any of the study investigators to become unblinded so that the FDA can be 
informed of subject assignment because of a SUSAR. 
 
L. Re-evaluation of Study: Not Applicable for this pilot study. 
 
M. Collection, monitoring, analysis and reporting of adverse events 
Adverse events, protocol deviations, unanticipated problems (UP), serious adverse events, 
sponsor and serious, are defined as described in NIH HRPP SOP 16 (“Reporting Requirements 
for Unanticipated Problems, Adverse Events and Protocol Deviations.”). All adverse events 
occurring during the study, including those observed by or reported to the research team, will be 
recorded. Serious unanticipated problems and serious protocol deviations will be reported to the 
IRB and CD as soon as possible but not more than 7 days after the PI first learns of the event. 
Not serious unanticipated problems will be reported to the IRB and CD as soon as possible but 
not more than 14 days after the PI first learns of the event. Not serious protocol deviations will 
be reported to the IRB as soon as possible but not more than 14 days after the PI first learns of 
the event. 
 
Deaths will be reported to the Clinical Director within 7 days after the PI first learns of 
the event. 
 
The PI and AIs will immediately report SAEs to the Sponsor according to the requirements of 21 
CFR 312.64(b) and as agreed upon with the sponsor. The PI will record nonserious AEs and 
report them to the Sponsor according to the timetable for reporting specified in the protocol (21 
CFR 312.64(b)). 
 


52 
 
a. Waiver of Reporting to the IRB of anticipated minor protocol deviations and minor 
adverse events (AE) 
The following anticipated minor deviations in the conduct of the protocol will not be 
reported to the IRB unless they occur at a rate greater than that which is anticipated to 
occur: 
Problem 
Expected Frequency 
Rescheduled appointment for protocol visit 
50% 
Unable to be contacted for follow up phone call 
20% 
Inability to obtain blood sample after 2 attempts 
25% 
Venous sample at a time point not obtained 
25% 
Bruising, fainting or lightheadedness after a blood draw 
10% 
Hemolysis or other issue preventing analysis of a blood or urine 
sample 
25% 
Stool sample not obtained or obtained on a different day 
25% 
Adequate subcutaneous adipose tissue sample not obtained 
25% 
Subject needs to make an additional visit for labwork (e.g. 
arrives too late for bloodwork, specimen result 
hemolyzed/equivocal, etc.) 
30% 
CT at time point not obtained 
15% 
Loss of investigational medications by subject 
15% 
Inadvertent loss of samples or data 
10% 
Appointment conducted >2 weeks beyond anticipated date 
10% 
Extra samples of blood drawn 
10% 
Inadvertent collection of additional data (e.g. extra survey, food 
record, stool sample, etc.) 
10% 
Becoming physically ill (e.g. abdominal pain, nausea, etc.) from 
consuming NIH CC food 
10% 
Sustaining minor bodily injury (e.g. twisted ankle) while 
participating in protocol 
5% 
Subject missed at least one dose but took at least 50% of study 
medication prescribed 
100% 
Subject took fewer than 50% of study medication prescribed 
15% 
Subject took an extra dose of study medication 
5% 
Subject forgot to return study medications at subsequent visit 
20% 


53 
 
Loss of, or forgot to bring back, MEMSCap 
20% 
MEMSCap not dispensed with open-label colchicine 
20% 
 
The following anticipated non-UP adverse events will not be reported to the IRB unless 
they occur at a rate greater than that known to occur in this population: 
i. Colchicine administration (events detailed in the FDA-approved package insert for 
colchicine): We anticipate that up to 30% of subjects will experience gastrointestinal 
side effects (e.g. diarrhea, abdominal pain, nausea, vomiting),68 which may require 
dose reductions to 0.6mg once daily. If this dose adjustment does not improve 
symptoms, it will be decided by patient and physician, on a case by case basis, 
whether to discontinue medication before the study is completed. Other anticipated 
adverse events from colchicine include: fatigue (4%), pharyngolaryngeal pain (3%), 
and headache (2%). Rare events (< 1%) may include alopecia, blood dyscrasias, 
hepatotoxicity, hypersensitivity reaction, neuromuscular toxicity (e.g. myalgia, 
myasthenia, myopathy, neuropathy, dizziness, rhabdomyolysis), and rash.68 
If the rate or severity of these events exceeds the rate or severity anticipated in the 
protocol or FDA-approved package insert, the events will be classified and reported as 
though they are Unanticipated Problems. 
 
Because we anticipate that other mild symptoms may occur in the course of 
participation in the protocol unrelated to study drug or participation, we will not 
submit Unanticipated Problems to mild signs/symptoms (CTCAE Grade ≤ 2), such as 
rhinorrhea, nasal congestion, watery eyes, cough, lightheadedness, mild wheezing, 
menstrual cramps, muscle weakness, fever blister, mild urinary tract infection, etc., 
that occur infrequently (≤ 10%).   
 
ii. OGTT: Infection (<5%), bruising (<30%), phlebitis (10%), nausea (10%), vomiting 
(10%), lightheadedness (10%).  
iii. FSIVGTT: Infection (<5%), bruising (<30%), phlebitis (10%), nausea (10%), 
vomiting (10%), hypoglycemia (10%), lightheadedness (10%), hunger (10%).  
iv. Fat Biopsy: Infection (<5%), bruising (<30%), bleeding (10%), nausea (10%), 
lightheadedness (10%), soreness (50%), local skin reaction (10%). 
v. Other: Skin reaction to EKG electrodes <15% 
 


54 
 
If the rate of these events exceeds the rate specified in the protocol, the events will be 
classified and reported as though they are Unanticipated Problems.  
 
b. Plan to monitor and report adverse events  
As outlined in Appendix A, for randomized and open-label subjects, adverse events will 
be monitored via telephone at one week, one month, and two months after the Baseline 
Visit using structured case report forms.  If any participant develops any concerning 
adverse events, the individual will be scheduled for an immediate clinic appointment 
with a trial investigator for further work up, as necessary.  Adverse events will also be 
assessed during the final visit via interim history and physical, as well as laboratory 
studies as described in Section IV C/D.  
 
Once 20 subjects have been enrolled into the randomized study, an interim analysis 
examining the rate of unanticipated problems and adverse events will be performed to 
evaluate whether they are occurring at a frequency greater than anticipated.   
 
c. DSMB 
A DSMB will be assembled for oversight of the randomized phase of this protocol by 
the Clinical Director, NICHD, with membership and scope determined by applicable 
institutional guidelines.  The DSMB will meet to evaluate all serious adverse events, and 
will at a minimum convene after at least 20 subjects have been enrolled.  The DSMB 
will examine whether there is evidence of safety and efficacy for colchicine.  The 
primary outcome measure that we propose the DSMB examine for efficacy is change in 
insulin sensitivity as determined from the FSIVGTT using the minimal model 
calculation.  For safety, the DSMB will review adverse event questionnaire data, and 
reports of side effects from all visits.  These reports will also be supplemented by a 
manual review by the investigators, who will add any other events not captured by these 
systems, and data files of laboratory values for CBC, acute care, hepatic, and mineral 
panels.  Results will be presented as an A vs. B analysis prepared by the data manager.  
The DSMB will be asked to prepare a detailed report to supply to the IRB that describes 
any adverse events discussed, and that explains the DSMB's vote to allow the study to 
continue or to end the study.  
 
N.  IND Monitoring Plan 


55 
 
1.   
Purpose 
The purpose of this Monitoring Plan is to describe the rationale and process for the collection, 
recording, and verification of data for NICHD Protocol, titled: Pilot study of the effects of 
colchicine in non-diabetic adults with metabolic syndrome. 
 
2.   
Objectives 
a. To establish a monitoring plan to ensure the protocol data are in compliance with 
Good Clinical Practice (GCP), NICHD Institutional Review Board (IRB) and 
Federal regulations.  
b. To ensure the validity, accuracy and integrity of the data 
 
 
3.   
Study Staff Responsibilities  
Jack A. Yanovski, MD, PhD (the principal investigator) is responsible for all aspects of the 
study. Some responsibilities may be delegated to the current associate investigator Andrew 
Demidowich, MD: 
 
Delegation of responsibility will be documented on a study staff Signature and Delegation of 
Responsibility Log.  
STUDY STAFF NAME 
TITLE 
*DELEGATED RESPONSIBILITIES 
Jack Yanovski, MD, PhD 
Principal-
Investigator 
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 
Andrew Demidowich, MD 
Lead Associate 
Investigator 
1, 2, 3, 4, 5, 6, 7, 8, 11, 12 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Jordan Levine, BS 
Co-investigator 
1, 6, 7, 8, 11 
 
 
 
 


56 
 
*Delegated Study Tasks:    
1. Obtain Informed 
Consent 
2. Obtain Medical History 
3. Perform Physical Exam 
4. Assess Eligibility Criteria 
5. Prescribe Study 
Drug/device 
6. CRF Completion  
7. CRF Queries 
8. Query completion 
9. Maintain Regulatory Docs  
10. Maintain IRB documents  
11. Data Monitoring 
12. Safety Monitoring  
 
 
4.   
Source Documentation and Case Report Forms 
Jack A. Yanovski, MD, PhD and Andrew Demidowich, MD are responsible for coordinating data 
collection and will review the data for accuracy and completeness within seven days of each 
subject visit.  
 
The PI (Jack A. Yanovski, MD, PhD) along with study co-investigator Andrew Demidowich, 
MD will conduct initial monitoring. Primary documents, Case Report Forms, and the 
Clinical Trials Database will also be audited per NICHD guidelines by Amarex. LLC. 
Patient consent documents, primary outcome and safety laboratory results, and diagnostic 
test results will be monitored for accuracy, correct dating, and agreement between case 
report forms and source documents. As case report forms are entered electronically into the 
NICHD Clinical Trials Database, the computer system contains logs indicating changes 
made and the circumstances leading to these changes. 
 
FDA regulatory requirements (annual reports, adverse events reporting, etc.) related to IND 
# 120722 (Colchicine) will also be monitored. The medical records of active subjects 
(defined as subjects receiving study medication) will be monitored quarterly or more 
frequently as required.  The FDA issues will be monitored at least annually. Any major 
findings will be summarized in writing and reported to the NICHD Institutional Review 
Board and DSMC, if indicated. Investigator credentials, training records, and the delegation 
of responsibility log will also be reviewed on an annual basis. 
 


57 
 
The NICHD Data Safety Monitoring Board will also conduct monitoring per NICHD 
guidelines. They will conduct A versus B analyses on data, but may also see unblinded data 
from the trial for their review of adverse events. 
 
5.   
IRB and DSMC Documentation  
All IRB documentation can be found in PTMS. The Principal Investigator, Jack A. 
Yanovski, MD, PhD, is responsible for maintaining IRB and DSMC correspondence related 
to this protocol, including records of all reviews of the study and submissions to the IRB and 
DSMC. 
 
6.   
FDA Documentation  
Jack A. Yanovski, MD, PhD is responsible for maintaining FDA correspondence, including 
forms 1571 and 1572 and other correspondence (e.g., annual reports, amendments, safety 
reports) in the electronic binder for IND # 120722 (Colchicine).  
 
Copies of all such correspondence are also maintained in PTMS as part of the NICHD protocol record. 
 
7.   
Adverse Event Procedures and Documentation  
Please refer to Section M of the protocol. 
 
8. Study Completion 
Upon completion of the study Jack A. Yanovski, MD, PhD will retain possession of the 
electronic IND binder and electronic Protocol Binder in a secure location. FDA requires 
records be retained for at least 2 years after study completion.  HHS regulations require that 
subjects’ records be maintained for at least three years after completion of a study. 
 


58 
 
Flyers, informational email and/or letters to 
previous subjects, newspaper 
advertisements 
Inclusion and exclusion criteria are 
reviewed.  If eligible, potential subjects 
scheduled for outpatient screening visit. 
Appendix A1– Study Design 
 
Event 
 
 
 
 
 
 
Procedure 
 
  
 
 
 
 
 
 
 
 
 
 
  
   
 
 
 
 
(within 4 weeks) 
 
 
 
 
 
 
(1 week) 
 
 
 
 
 
(3 weeks later) 
 
 
 
 
 
 
 
 
 
 (1 month) 
 
 
 
 
 
 (1 month) 
 
 
 
 
 
 (3 months) 
Study advertisement 
Telephone screening 
In clinic/5-SWS Day Hospital: Interim 
H&P, baseline labs, FSIVGTT, and SAT 
biopsy will take place all on the same day.  
For subjects eligible for randomization, a 
55 day supply of pills given to subject, 
randomized to either placebo or colchicine.  
In clinic/5-SWS Day Hospital: H&P, initial 
protocol review, EKG, body composition 
DEXA, screening labs, OGTT.   
Phone Call (randomized and open-label 
subjects)
Outpatient screening visit 
By investigator: to assess for adverse 
events and adherence/tolerability.  
Baseline visit 
Interim Safety Visit (randomized and open-
label subjects)
Phone Call (randomized and open-label 
subjects) 
Final visit (randomized and open-label 
subjects) 
In 5-SWS Day Hospital: Interim H&P, 
labs, FSIVGTT, body composition DEXA, 
and SAT biopsy will take place all on the 
same day. Pill bottle will be collected from 
patient and study treatment will be 
terminated. 
In clinic/5-SWS Day Hospital: Interim 
H&P, assess for adverse events and 
adherence/tolerability, check safety labs 
(e.g. CBC, acute care and hepatic panels, 
CK). 55 day supply of pills will be given to 
the subject. 
Washout visit (optional) and discharge  
(randomized and open-label subjects) 
In 5-SWSDH: Interim H&P, labs, 
FSIVGTT, DEXA, and SAT biopsy. 


59 
 
Performed at Time 0 of the 2 hour OGTT. 
Performed in Day Hospital. 
Schedule baseline visit if subject qualifies 
Page Protocol team on arrival of patient.  
Accurate height x3 and weight.  H&P 
performed. 
Protocol is reviewed by research team, and 
consent is signed formally with witness 
present.   
Performed in Day Hospital 
Performed on 7th floor, Metabolic Unit 
Appendix A2 – Screening Visit Flowsheet 
 
                     Event 
 
 
 
 
 
 
 
Procedure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fasting blood draw 
2 hour oral glucose tolerance test 
Discharge from NIH 
Arrive to NIH 5-SWS Day Hospital by 
8AM 
Protocol Review 
EKG 
DXA Scan 


60 
 
Performed at Time -15 min of the 
FSIVGTT 
Performed in Day Hospital. 
Page Protocol team on arrival of patient.  
Accurate height x3 and weight.  Interval 
H&P performed. 
Performed by a study investigator. 
Performed in Radiology 
Performed in Day Hospital. Stool sample 
collected in Day Hospital if subject did not 
bring sample from home. 
Appendix A3 – Baseline Visit Flowsheet 
 
                     Event 
 
 
 
 
 
 
 
Procedure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fasting blood draw  
FSIVGTT 
Stool sample and  
Hollingshead Questionnaire 
Arrive to NIH 5-SWS Day Hospital by 
8AM 
Subcutaneous Adipose Tissue Biopsy 
CT Scan 
Discharge from NIH 


61 
 
Page Protocol team on arrival of patient.  
Accurate height x3 and weight.  Interval 
H&P performed. 
Performed in Day Hospital. 
Appendix A4 – Interim Safety Visit Flowsheet (randomized and open-label only) 
 
                     Event 
 
 
 
 
 
 
 
Procedure 
 
 
 
 
 
 
 
 
 
 
 
Arrive to NIH 5-SWS Day Hospital by 
8AM 
Fasting blood draw 
Discharge from NIH 


62 
 
Performed by a study investigator. 
Performed at Time -15 min of the 
FSIVGTT 
Page Protocol team on arrival of patient.  
Accurate height x3 and weight.  Interval 
H&P performed. 
Performed in Day Hospital. 
Performed on 7th floor, Metabolic Unit 
Performed in Radiology 
Performed in Day Hospital. 
Appendix A5 – Final Visit Flowsheet (randomized and open-label only) 
 
                     Event 
 
 
 
 
 
 
 
Procedure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subcutaneous Adipose Tissue Biopsy 
Fasting blood draw  
DXA Scan 
FSIVGTT 
Arrive to NIH 5-SWS Day Hospital by 
8AM 
CT Scan 
Exit Questionnaire 
Discharge from NIH 
Stool sample  
Collected in Day Hospital if patient did not 
bring sample from home. 


63 
 
Performed by a study investigator. 
 
Performed at Time -15 min of the 
FSIVGTT 
Page Protocol team on arrival of patient.  
Accurate height x3 and weight.  Interval 
H&P performed. 
Performed in Day Hospital. 
 
Performed on 7th floor, Metabolic Unit 
 
Performed in Radiology 
 
Appendix A6 – Optional Washout Visit Flowsheet (randomized and open-label 
only) 
 
                     Event 
 
 
 
 
 
 
 
Procedure 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subcutaneous Adipose Tissue Biopsy 
Fasting blood draw  
DXA Scan 
FSIVGTT 
Arrive to NIH 5-SWS Day Hospital by 
8AM 
CT Scan 
Discharge from NIH 
Stool sample  
Collected in Day Hospital if patient did not 
bring sample from home. 


64 
 
Appendix B1 
 
 Potentially Significant Drug Interactions with Colchicine 
 
Drug 
Noted or Anticipated Outcome 
Strong CYP3A4 Inhibitors 
 
Atazanavir 
Clarithromycin 
Cimetidine 
Cobicistat 
Darunavir/Ritonavir 
Indinavir 
Itraconazole 
Ketoconazole 
Lopinavir/Ritonavir 
Nefazodone 
Nelfinavir 
Ritonavir 
Saquinavir 
Telaprevir 
Telithromycin 
Tipranavir/Ritonavir 
Tolbutamide 
Significant increase in colchicine plasma levels; fatal colchicine toxicity 
has been reported with clarithromycin, a strong CYP3A4 inhibitor. 
Similarly, significant increase in colchicine plasma levels is anticipated 
with other strong CYP3A4 inhibitors. 
 
 
Moderate CYP3A4 Inhibitors 
 
Amprenavir 
Aprepitant 
Azithromycin 
Diltiazem 
Erythromycin 
Fluconazole 
Fosamprenavir 
Grapefruit Juice 
Verapamil 
Significant increase in colchicine plasma concentration is anticipated. 
Neuromuscular toxicity has been reported with diltiazem and verapamil 
interactions. 
 
 
P-gp Inhibitors 
Significant increase in colchicine plasma levels; fatal colchicine toxicity 
has been reported with cyclosporine, a P-gp inhibitor. Similarly, significant 
increase in colchicine plasma levels is anticipated with other P-gp 
inhibitors. 
Cyclosporine 
Ranolazine 
 
HMG-Co A Reductase Inhibitors 
 
Atorvastatin 
Fluvastatin 
Lovastatin 
Pitavastatin 
Pravastatin 
Rosuvastatin 
Simvastatin 
The addition of one drug to a stable long-term regimen of the other has 
resulted in myopathy and rhabdomyolysis (including a fatality). 
 
 
Other Lipid Lowering Drugs 
The addition of one drug to a stable long-term regimen of the other has 
resulted in myopathy and rhabdomyolysis (including a fatality). 
Fibrates 
Gemfibrozil 
 
 
Digitalis Glycosides 
 
Digoxin 
Rhabdomyolysis has been reported. 
 
 


65 
 
Other 
Dasatinib 
Fusiric Acid (systemic) 
Ivacaftor 
Mifepristone 
 
 
Combination with colchicine may increase CYP3A4 substrates. 
Other (con’t) 
Aripiprazole 
Axitinib 
Cyanocobalamin 
Saxagliptin 
 
 
Colchicine may cause a decrease in serum concentrations. 
 
 


66 
 
Appendix B2 
 
 Medications that may confound the assessment for diabetes  
 
Thiazide diuretics at a dose greater than 25mg/day 
Systemic non-cardioselective beta-blockers 
- 
Carvedilol 
- 
Labetalol 
- 
Nadolol  
- 
Penbutolol Sulfate 
- 
Pindolol  
- 
Propanolol  
- 
Timolol 
 
Niacin 
Systemic glucocorticoids 
Prescription or over-the-counter weight loss or weight gain medications/supplements 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


67 
 
Appendix C- Surgical/Invasive Procedure Verification Checklist 
 
Date:  
 
Time:  
Procedure (PER CONSENT):  
Responsible Physician(s)/LIP(s):  
Surgical Site(s) Marked: 
 
 
  
INSTRUCTIONS: Check the boxes and sign in the appropriate boxes below to indicate the steps that have been completed. Do not 
continue with the process unless you are able to verify that each step has been completed as appropriate. 
 
Step  
  
Verification Process  
 
Signature of Care Team 
Member Documenting the 
Information 
Pre-Procedure Area:  
1)  
Identification of Correct:   
Yes  
N/A  
  
  
Patient  
  
  
  
  
Procedure  
  
  
 
  
Side, site, and level (if appropriate)  
  
  
 
2)  
Surgical Site and/or Side Marked  
  
  
  
3)  
Appropriate documents confirming the procedure side, site, and level 
where appropriate are present (for example, history and physical, nursing 
assessment, and pre-anesthesia assessment)  
  
  
 
  
Accurately completed, and signed, procedure consent form  
  
  
 
  
Correct diagnostic and radiology test results(for example, radiology 
images and scans, or pathology and biopsy reports) are properly labeled 
and available  
  
  
 
  
Required blood products, implants, devices, and/or special equipment for 
the procedure are available  
  
  
 
Immediately Prior to the Start of the Surgery/Invasive Procedure:  
4)  
“Time Out” – Prior to the procedure in the operating room/procedure 
area, ALL TEAM MEMBERS participate together in a time out to 
verbally verify:  
  
Yes  
  
N/A  
  
  
Correct patient identity  
  
  
  
  
Correct side, site, and level are marked as appropriate  
  
  
 
  
Accurately completed, and signed, procedure consent form  
  
  
 
  
Agreement on the procedure to be performed  
  
  
 
  
Correct patient position  
  
  
 
  
Availability of appropriately labeled relevant images and tests  
  
  
 
  
The need for antibiotics or fluids for irrigation purposes  
  
  
 
  
Safety precautions based on patient history or medication use  
  
  
 
*COMPLETE THIS SECTION ONLY IF UNABLE TO COMPLETE A STEP IN THE VERIFICATION PROCESS 
ABOVE – EXPLAIN WHY  
Step  
Explanation  
Signature  of Care Team Member 
Documenting the Information  
Date  
 
 
 
 


68 
 
Appendix D 
3-Month Visit (Final Visit) Exit Questionnaire 
Date _____/_____/_____ 
 
Dear Study Participant, 
 
You recently completed a research study where half of the study participants took colchicine and 
half took placebo capsules for three months.  We would like to ask you some questions about your 
feelings and attitudes about the study.  With your help we hope to be able to improve our studies in 
the future.  Please answer all questions as honestly as possible. 
 
1. 
Which capsule (colchicine or placebo) do you think you were taking?  
Check one 
 
_____  colchicine 
 
_____  placebo 
 
Why do you think so? _____________________________________________________ 
 
2. 
How sure or unsure are you about which capsules you were taking? 
 
Circle one: 
 
3. 
When you agreed to join the study, do you think that you fully understood the study and 
everything you would need to do?     Check one: 
 
 
_____ yes 
 
_____ no 
 
 
 
If no, what didn’t you understand? ___________________________________________ 
 
4. 
Knowing what you know now, if you could do it all over again, would you join this study?      
Check one: 
 
 
_____  yes 
 
_____  no 
 
5. 
What would you tell a friend who was thinking of entering the study?  Check one: 
 
 
_____  join the study  
_____  don’t join the study 
1 
2 
3 
4 
5 
Very unsure 
Somewhat 
 unsure 
Undecided 
Somewhat 
sure 
Very sure 


69 
 
 
6. 
Suppose we knew for sure that taking colchicine could help you lose one pound per year, or 
at least keep you from gaining a pound or two.  Would it be worth the effort of taking the 
colchicine? 
 
 
______ yes 
 
______ no 
 
 
7. 
Do you feel your overall health has improved due to being in the study? 
 
 
______yes 
 
______no 
 
 
8. 
What effect do you think the capsules had on your body weight? 
 
 
______ no effect 
______ lost weight 
______ gained weight  
 
9. 
If you lost weight, what do you think was the reason? 
 
Check all that apply 
 
 
______ study capsules 
     ______ changed eating habits 
 
 
______ exercise 
other (please list) _______________________________________ 
 
10. 
If you tried any special diets or weight loss supplements during the three month period 
please describe (for example, Atkins, low fat, low carb, meal bars): 
 
 
________________________________________________________________________ 
 
11. 
Do you feel the study capsules improved any of the following in you? (check all that apply): 
 
 
______ joint pain 
 
______ sense of taste 
 
 
______ mobility 
 
______ energy 
 
 
If yes, please explain: ______________________________________________________ 
 
12. 
Do you think the study capsules had any side effects? 
 
 
______ yes 
 
______ no 
 
 
If yes, please list: _________________________________________________________ 
 


70 
 
________________________________________________________________________ 
 
13. 
Did you find the alarm clock useful to help remind you to take your medication?   
(check one): 
 
 
______ yes 
 
______ no 
 
 
If no, why not? __________________________________________________________ 
 
________________________________________________________________________ 
 
14.   
Why did you decide to be part of the study? 
Rank in order of importance (1 for first choice, 2 for second choice, etc.)  
Leave blank if the reason does not apply to you at all: 
 
 
______  wanted to improve my health 
 
______  make a contribution to science / help other people 
 
______  try to lose weight 
 
______  financial compensation 
 
______  opportunity for medical care at no cost 
 
______  wanted to take colchicine 
 
______  other: ___________________________________________________________ 
 
15. 
What was the worst part of the study?   
 
Rank in order of importance (1 for first choice, 2 for second choice, etc.)  
 
Leave blank if item does not apply to you: 
 
 
______  coming to NIH (traveling, security checks) 
 
______  taking the capsules 
 
______  blood draws 
 
______  FSIVGTT (3 hour IV glucose test) 
 
______  Fat biopsy 
 
______  DEXA (body fat) scan 
 
______  Collecting the stool sample 
 
______  physical exams and body measurements 
 
______  appointment times/having to take time off from work 
 
______  filling out questionnaires 
 
______  didn’t get the results I was expecting from the study capsules 
 
______  other: ___________________________________________________________ 
 


71 
 
16. 
We know that for most people it is difficult to take every capsule on time every day and you 
probably missed some doses. What do you think might have helped you to be better at 
taking the capsules?  (check all that apply): 
 
 
 
______if I only had to take one capsule a day instead of two 
 
 
______if I could have taken the two capsules together, once a day 
 
 
______if the capsules were smaller 
 
 
______if the capsules were easier to swallow 
 
 
______if it were easier to remember to take the capsules 
 
______  other: ________________________________________________________ 
 
Please tell us anything else that may have helped you to do a better job of taking your 
capsules 
 
 
  
____________________________________________________________________ 
 
 
17. 
Please write in any other comments or suggestions for the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
________________________________________________________________________ 
 
THANK YOU FOR BEING A PART OF THE STUDY 


72 
 
3-Month Visit (Final Visit) Exit Questionnaire for T2DM Open Label Arm 
 
Date _____/_____/_____ 
 
Dear Study Participant, 
 
You recently completed a research study where study participants took colchicine capsules for three 
months.  We would like to ask you some questions about your feelings and attitudes about the 
study.  With your help we hope to be able to improve our studies in the future.  Please answer all 
questions as honestly as possible. 
 
1. 
When you agreed to join the study, do you think that you fully understood the study and 
everything you would need to do?     Check one: 
 
 
_____ yes 
 
_____ no 
 
 
 
If no, what didn’t you understand? ___________________________________________ 
 
2. 
Knowing what you know now, if you could do it all over again, would you join this study?      
Check one: 
 
 
_____  yes 
 
_____  no 
 
3. 
What would you tell a friend who was thinking of entering the study?  Check one: 
 
 
_____  join the study  
_____  don’t join the study 
 
4. 
Suppose we knew for sure that taking colchicine could help you lose one pound per year, or 
at least keep you from gaining a pound or two.  Would it be worth the effort of taking the 
colchicine? 
 
 
______ yes 
 
______ no 
 
 
7. 
Do you feel your overall health has improved due to being in the study? 
 
 
______yes 
 
______no 
 
 
8. 
What effect do you think the capsules had on your body weight? 
 
 
______ no effect 
______ lost weight 
______ gained weight  
 


73 
 
9. 
If you lost weight, what do you think was the reason? 
 
Check all that apply 
 
 
______ study capsules 
     ______ changed eating habits 
 
 
______ exercise 
other (please list) _______________________________________ 
 
10. 
If you tried any special diets or weight loss supplements during the three month period 
please describe (for example, Atkins, low fat, low carb, meal bars): 
 
 
________________________________________________________________________ 
 
11. 
Do you feel the study capsules improved any of the following in you? (check all that apply): 
 
 
______ joint pain 
 
______ sense of taste 
 
 
______ mobility 
 
______ energy 
 
 
If yes, please explain: ______________________________________________________ 
 
12. 
Do you think the study capsules had any side effects? 
 
 
______ yes 
 
______ no 
 
 
If yes, please list: _________________________________________________________ 
 
________________________________________________________________________ 
 
13. 
Did you find the alarm clock useful to help remind you to take your medication?   
(check one): 
 
 
______ yes 
 
______ no 
 
 
If no, why not? __________________________________________________________ 
 
________________________________________________________________________ 
 
 
 
 
 


74 
 
14.   
Why did you decide to be part of the study? 
Rank in order of importance (1 for first choice, 2 for second choice, etc.)  
Leave blank if the reason does not apply to you at all: 
 
 
______  wanted to improve my health 
 
______  make a contribution to science / help other people 
 
______  try to lose weight 
 
______  financial compensation 
 
______  opportunity for medical care at no cost 
 
______  wanted to take colchicine 
 
______  other: ___________________________________________________________ 
 
15. 
What was the worst part of the study?   
 
Rank in order of importance (1 for first choice, 2 for second choice, etc.)  
 
Leave blank if item does not apply to you: 
 
 
______  coming to NIH (traveling, security checks) 
 
______  taking the capsules 
 
______  blood draws 
 
______  FSIVGTT (3 hour IV glucose test) 
 
______  Fat biopsy 
 
______  DEXA (body fat) scan 
 
______  Collecting the stool sample 
 
______  physical exams and body measurements 
 
______  appointment times/having to take time off from work 
 
______  filling out questionnaires 
 
______  didn’t get the results I was expecting from the study capsules 
 
______  other: ___________________________________________________________ 
 
16. 
We know that for most people it is difficult to take every capsule on time every day and you 
probably missed some doses. What do you think might have helped you to be better at 
taking the capsules?  (check all that apply): 
 
 
 
______if I only had to take one capsule a day instead of two 
 
 
______if I could have taken the two capsules together, once a day 
 
 
______if the capsules were smaller 
 
 
______if the capsules were easier to swallow 
 
 
______if it were easier to remember to take the capsules 
 
______  other: ________________________________________________________ 
 


75 
 
Please tell us anything else that may have helped you to do a better job of taking your 
capsules 
 
 
  
____________________________________________________________________ 
 
 
17. 
Please write in any other comments or suggestions for the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
________________________________________________________________________ 
 
THANK YOU FOR BEING A PART OF THE STUDY 
 


76 
 
 
Appendix E 
MEDICATION GUIDE  
Congratulations on starting your involvement with our research protocol!  Participants in the 
Randomization Arm of this study have been randomized to receive either the research medication 
(colchicine) 0.6 mg capsules twice a day or a placebo.  Neither the study subjects nor the 
investigators know which “version” of the research medication you are receiving.  Participants in 
the Open-Label Arm of the study will be taking colchicine 0.6 mg capsules twice a day 
Read this Medication Guide before you start taking the medication.  This Guide does not take the 
place of talking to your healthcare provider or the NIH research team about your medical 
conditions or treatment. You should let your healthcare provider know that you may be taking the 
research medication as part of a research protocol.  
What is the most important information I should know about the research medication?  
The research medication can cause serious side effects or death if levels of the research 
medication are too high in your body.  
• 
Taking certain medicines with the research medication can cause your level of the research 
medication to be too high, especially if you have kidney or liver problems.  
• 
Tell the NIH research team about all your medical conditions, including if you have kidney 
or liver problems. Your dose of the research medication may need to be changed.  
• 
Tell the NIH research team about all the medicines you take, including prescription and non-
prescription medicines, vitamins and herbal supplements.  
• 
Even medicines that you take for a short period of time, such as antibiotics, can interact with 
the research medication and cause serious side effects or death.  
• 
Talk to the NIH research team, your healthcare provider, and pharmacist before taking any 
new medicine. 
  
• 
Especially tell the NIH research team if you take:  
• atazanavir sulfate (Reyataz
®
)  
 
 
• clarithromycin (Biaxin
®
)  
• cyclosporine (Neoral
®
, Gengraf
®
, Sandimmune
®
)  • darunavir (Prezista
®
)  
• fosamprenavir (Lexiva
®
) with ritonavir  
 
• fosamprenavir (Lexiva
®
)  
• indinavir (Crixivan
®
)  
 
 
 
• itraconazole (Sporanox
®
)  
• ketoconazole (Nizoral
®
) 
 
 
 
• lopinavir/ritonavir (Kaletra
®
)  
• nefazodone (Serzone
®
)  
 
 
 
• nelfinavir mesylate (Viracept
®
)  
• ritonavir (Norvir
®
)   
 
 
 
• saquinavir mesylate (Invirase
®
)  
• telithromycin (Ketek
®
)  
 
 
 
• tipranavir (Aptivus
®
)  


77 
 
 
Ask the NIH research team, your healthcare provider, or pharmacist if you are not sure if you 
take any of the medicines listed above. This is not a complete list of all the medicines that can 
interact with the research medication.  
 
• 
Know the medicines you take. Keep a list of them and show it to your healthcare provider 
and pharmacist when you get a new medicine.  
• 
Keep the research medication out of the reach of children.  
 
Who should not take the research medication?  
Do not take the research medication if you have liver or kidney problems and you take certain other 
medicines. Serious side effects, including death, have been reported in these patients even when 
taken as directed. See “What is the most important information I should know about the research 
medication?”  
What should I tell the NIH research team before starting the research medication?  
See “What is the most important information I should know about the research medication?”  
Before you take the research medication tell the NIH research team about all of your medical 
conditions including if you:  
• 
have liver or kidney problems  
• 
are pregnant or plan to become pregnant. It is not known if the research medication will 
harm your unborn baby. Please tell the NIH research team immediately if you are pregnant 
or plan to become pregnant.  
• 
are breast-feeding or plan to breast-feed. The research medication passes into your breast 
milk. Due to the possible risks to the child, you are not eligible for this study if you are 
nursing. 
 
Using the research medication with certain other medicines, such as cholesterol-lowering 
medications or digoxin, can affect each other causing serious side effects.  Talk to the NIH research 
team and your healthcare provider about whether the medications you are taking might interact with 
the research medication, and what side effects to look for.  
How should I take the research medication?  
• 
Take the research medication exactly as the NIH research team instructs you to take it. If 
you are not sure about your dosing, call the NIH research team. 
• 
The medication can be taken with or without food.  
• 
If you take too much the research medication go to the nearest hospital emergency room 
right away.  
• 
If you miss a dose, then take it as soon as you remember. If it is almost time for your next 
dose, just skip the missed dose. Take the next dose at your regular time. Do not take 2 doses 
at the same time.  
 
What should I avoid while taking the research medication?  
Avoid eating grapefruit or drinking grapefruit juice while taking the research medication. It can 
increase your chances of getting serious side effects.  


78 
 
What are the possible side effects of the research medication?  
The research medication can cause serious side effects or even cause death. See “What is the 
most important information I should know about the research medication?”  
Get medical help right away, if you have:  
• 
Muscle weakness or pain  
• 
Numbness or tingling in your fingers or toes  
• 
Unusual bleeding or bruising  
• 
Increased infections  
• 
Feel weak or tired  
• 
Have significant dizziness 
• 
Pale or gray color to your lips, tongue, or palms of your hands  
• 
Severe diarrhea or vomiting  
 
The most common side effects of the research medication are abdominal pain, diarrhea, nausea 
and vomiting.  
Tell the NIH research team if you have any side effect that bothers you or that does not go away.  
These are not all of the possible side effects of the research medication. For more information, 
ask the NIH research team, your healthcare provider, or pharmacist.  
How should I store the research medication?  
• 
Store at room temperature between 68° and 77°F (20° to 25°C).  
• 
Keep tightly closed in the provided container.  
• 
Keep out of the light.  
 
Keep the research medication and all medicines out of the reach of children.  
 


79 
 
Appendix F 
(Adapted from Common Terminology Criteria for Adverse Events v4.0 (CTCAE) 
Publish Date: May 28, 2009) 
 
Grades 
 
Grade refers to the severity of the adverse event (AE). The CTCAE displays Grades 1 through 5 with unique 
clinical descriptions of severity for each AE based on this general guideline: 
 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated. 
 
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental Activities of Daily Living (ADL)*. 
 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation 
of hospitalization indicated; disabling; limiting self-care ADL**. 
 
Grade 4: Life-threatening consequences; urgent intervention indicated. 
 
Grade 5: Death related to AE. 
 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
 


80 
 
Appendix G 
 
You will be completing Self Sampling at home (or at the NIH) for up to 4 visits as part of the 
colchicine study: 
 Screening Visit 
 Medication Initiation Visit 
 3 month Final (Medication Completed) Visit 
 6 month Washout Visit (Optional) 
 
 
Supply list for Stool Collection: 
 
1. Fecocainter stool container with toilet “frame” 
2. Brown Top Stool Collection Vial (x3) 
3. Permanent Marker 
4. Clear Bag for stool collection vial (biohazard bag) 
5. Disposable gloves 
6. Stool sampling instructions 
7. Food Dietary record + instructions 
 
 
For Questions Contact: 
Jordan Levine, Research Coordinator 
 
 
[Phone Number Written Here] 
 
jordan.levine@nih.gov 
Ginika Onyekaba, Research Coordinator 
 
 
[Phone Number Written Here] 
ginikanwa.onyekaba@nih.gov 
Andrew Demidowich, MD, Lead Associate Investigator 
[Phone Number Written Here] 
andrew.demidowich@nih.gov 
  
 
 


81 
 
STOOL SPECIMEN COLLECTION: 
1. Wash your hands. 
2. Label your brown-lid container with the date and time of collection using the 
permanent marker provided. The inside of the container is sterile until opened. 
 
 
3. To minimize urine collection, first empty your bladder before performing the next 
steps. 
 
4. Place the stool-collecting frame and Fecocontainer into the toilet, securely under 
the seat.  
          
                       
 
5. Take a bowel movement in the bowl.  


82 
 
 
6. Put on gloves. 
 
7. As shown in Figure A, unscrew the cap carefully to avoid spilling fluid.  Use the 
small spoon attachment on the lid to scoop up a “pea size” sample. Place the 
shovel with the sample into the specimen container, and secure the lid tightly and 
shake vial for 5 seconds.  Try not to spill any of the liquid inside the vial (it helps 
preserve the stool).   
 
               
  
 
8. Repeat two more times for a total of three stool vials.  Uncap and work with only 
ONE vial at a time.  
9. Place all three stool vials into the biospecimen bag provided. 
 
A 
B 
C 


83 
 
10. Dispose of remaining feces into toilet and flush (optional).  Close Fecocontainer 
with the lid provided and throw away into a garbage bag. Throw the gloves away in 
the same bag. Wash Hands. 
  
11. Return stool samples during your scheduled clinic visit.  Because the vials have the 
special preservative, they do not need to be refrigerated or frozen.  However, you 
put the bag in the freezer if you wish.   


84 
 
Colchicine Study (14-CH-0119) 
Keeping Food Records 
 
 
To better understand what you usually eat and drink when you are not in the hospital, 
please write down everything you eat and drink for a typical day. 
 
When should the food records be kept?   Write down all foods and beverages you 
consume for 24 hours before you come to the Clinical Center for your appointment. This 
day should represent a fairly typical day for you.   
 
Eat normally on this day.  Don’t change your food choices, methods of food preparation, or 
where you eat just because you are recording your intake. There is no right or wrong way 
to eat for this evaluation. 
 
How and what should be recorded?  Use a new form each day.  It is best to record what 
you eat immediately after each meal and snack. 
 
You should write down: 
 
• the time you begin eating each meal and snack 
• all foods and beverages, except for plain water. 
• all condiments (such as ketchup, margarine, mayonnaise, salad dressing, sauces, 
gravy,  sugar, etc).  You do not need to record salt, pepper, herbs and spices. 
• all medicines, vitamins, minerals, and/or other supplements taken. 
 
 
For each food and beverage that you list, include an amount and a description.  To guide 
you, refer to the sample food record and the hints for recording amounts and description 
information on the next few pages.  
 
What do I do with the forms after they are filled out?   Bring them back with you to the 
NIH when you come next time.  
 
 
If you have any questions or concerns, please contact me by e-mail or by phone. 
 
 
 
 
 
Dietitian’s name:_Amber Courville______ 
Phone number: _ 301-594-8051 _________ 
E-mail: __ courvillea@nih.cc.gov _______________ 


85 
 
Hints for Completing the Amount Column 
 
 
A.  Measure foods after preparation and cooking is completed. 
 
B.  Measurements can be listed in 4 ways: 
 
 
1.  The number of items. 
 
 
 
Examples: 
saltines  
6 
 
 
 
 
white bread 2 slices 
 
 
 
 
grapes 
12 
 
 
 
 
ketchup 
2 packets 
 
 
2.  In household measures, using standard level measuring cups and spoons. 
 
 
 
Examples: 
applesauce 1/3 cup 
 
 
 
 
popcorn 
3 cups 
 
 
 
 
jelly 
 
1 ½  TB [tablespoons] 
 
 
 
 
2% milk 
1.5 CP [cup] 
 
 
 
(Do not use non-standard measures like “handful” or “serving”) 
 
 
3.  By weight or by volume, as listed on a package (or by using a kitchen scale if         
      
you have one).  
 
 
 
Examples: 
ginger ale 
12 FL OZ [fluid ounces] 
 
 
 
 
yogurt  
4.5 oz [ounces] 
 
 
 
 
Almond Joy 49 gm [grams] 
 
 
 
 
roast beef 
2 ½  oz 
 
 
 
 
pretzels 
1/3 of 6.5 oz bag 
 
 
 
 
 
 
4.  By dimensions, using a ruler. 
 
 
 
Examples: 
pancake 
5” diameter 
 
 
 
 
meatball 
1 ¼” diameter 
 
 
 
 
lasagna  
3 ½” x 4” x 1½” cube 
 
 
 
 
pizza  
1/8 of 14” diameter  [or draw it with dimensions] 
 
 
 
 
 
 
 
• Remember not all food that is served is eaten, and at other times, you may go back for seconds.  
You may need to adjust portion sizes to reflect the amount you actually ate. 
 
 


86 
 
Hints for Completing the Description Column 
 
A.  Describe foods completely. 
 
Examples: 
 
 
 
sirloin steak, fat partially trimmed 
 
 
80% lean ground beef (or 80/20 ground beef) 
 
 
chicken drumstick, skin removed before cooking 
 
 
reduced fat or 2% milk 
 
 
baked potato, skin eaten 
 
 
carrot cake with cream cheese frosting 
 
B.  Include brand names whenever possible.  Also include terms like calcium-fortified, light, and 
reduced calorie if listed on the label. 
 
Examples: 
 
 
Country Crock Light spread tub margarine  
Oreo reduced-fat cookies 
Miller Lite draft beer 
 
 
Hellmann’s fat-free cholesterol-free mayonnaise 
 
 
Dannon lowfat fruited yogurt 
 
 
sliced peaches in light syrup 
 
C.  Include information about preparation and cooking methods. 
 
Examples: 
 
 
skinless chicken breast 
floured and pan-fried in corn oil 
 
 
canned corn  
 
tub margarine and sugar added 
 
 
Campbell’s tomato soup 
made with water 
 
 
mac and cheese 
 
from mix, made with whole  milk and  
 
 
 
 
 
 
 
       Parkay stick margarine 
 
D.  For mixed dishes and recipe items, you only need to list major ingredients.  You do not need to 
write down the entire recipe. 
 
Examples: 
 
 
potato salad  
 
made with potatoes, eggs, regular mayo 
 
 
chocolate chip cookies 
homemade with real butter, walnuts added 
 
 
meatloaf 
 
 
made with 85/15 ground beef, oatmeal,   
 
 
 
 
 
      
   ketchup, egg 
 
E.  For fast food items from major chains, you only need to name the item.  No description is 
necessary, unless you “special order” an item.  Also, note if all of it wasn’t eaten. 
 
Examples: 
 
 
Biggie Fries (Wendy’s) 
 
 
 
Quarter Pounder with Cheese (McDonald’s) - didn’t eat pickles 
 
 
Meat-lovers Pan Pizza (Pizza Hut) 
 
F.  Remember to record any additions made at the table, such as margarine, sugar, ketchup, 
mustard, sauces, mayonnaise.  List them separately, and include amounts. 
 




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beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and beta-cell Function in type 
2 diabetic patients. Diabetes 2013;62:3027-32. 
106. 
Anderson RL, Hamman RF, Savage PJ, et al. Exploration of simple insulin sensitivity 
measures derived from frequently sampled intravenous glucose tolerance (FSIGT) tests. The 
Insulin Resistance Atherosclerosis Study. Am J Epidemiol 1995;142:724-32. 
107. 
Saad MF, Anderson RL, Laws A, et al. A comparison between the minimal model and 
the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose 
tolerance. Insulin Resistance Atherosclerosis Study. Diabetes 1994;43:1114-21. 
108. 
Yang YJ, Youn JH, Bergman RN. Modified protocols improve insulin sensitivity 
estimation using the minimal model. Am J Physiol 1987;253:E595-602. 


94 
 
109. 
Korytkowski MT, Berga SL, Horwitz MJ. Comparison of the minimal model and the 
hyperglycemic clamp for measuring insulin sensitivity and acute insulin response to glucose. 
Metabolism 1995;44:1121-5. 
110. 
Coates PA, Luzio SD, Brunel P, Owens DR. Comparison of estimates of insulin 
sensitivity from minimal model analysis of the insulin-modified frequently sampled intravenous 
glucose tolerance test and the isoglycemic hyperinsulinemic clamp in subjects with NIDDM. 
Diabetes 1995;44:631-5. 
111. 
Davidson LE, Kuk JL, Church TS, Ross R. Protocol for measurement of liver fat by 
computed tomography. Journal of applied physiology 2006;100:864-8. 
112. 
Speliotes EK, Massaro JM, Hoffmann U, et al. Liver fat is reproducibly measured using 
computed tomography in the Framingham Heart Study. Journal of gastroenterology and 
hepatology 2008;23:894-9. 
113. 
Fujimoto WY, Jablonski KA, Bray GA, et al. Body size and shape changes and the risk 
of diabetes in the diabetes prevention program. Diabetes 2007;56:1680-5. 
114. 
Common Terminology Criteria for Adverse Events (CTCAE) v4.03. In: National Cancer 
Institute, National Institutes Health, ed. Bethesda, MD: U.S. Department of Health and Human 
Services; 2010. 
115. 
Perry M. In: Williams, Wilkins, eds. The Chemotherapy Sourcebook. Baltimore; 1992 
1133-40. 
116. 
Essah PA, Arrowood JA, Cheang KI, Adawadkar SS, Stovall DW, Nestler JE. Effect of 
combined metformin and oral contraceptive therapy on metabolic factors and endothelial 
function in overweight and obese women with polycystic ovary syndrome. Fertility and sterility 
2011;96:501-4 e2. 
117. 
Mitri J, Dawson-Hughes B, Hu FB, Pittas AG. Effects of vitamin D and calcium 
supplementation on pancreatic beta cell function, insulin sensitivity, and glycemia in adults at 
high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized 
controlled trial. Am J Clin Nutr 2011;94:486-94. 
118. 
O'Keefe JH, Jr., McCallister BD, Bateman TM, Kuhnlein DL, Ligon RW, Hartzler GO. 
Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty. J Am 
Coll Cardiol 1992;19:1597-600. 
119. 
Chappey ON, Niel E, Wautier JL, et al. Colchicine disposition in human leukocytes after 
single and multiple oral administration. Clin Pharmacol Ther 1993;54:360-7. 
 

ICF_001.pdf: 
 
 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
               •  Adult Patient or     •  Parent, for Minor Patient 
 
 
INSTITUTE: 
National Institute of Child Health and Human Development 
 
 
STUDY NUMBER: 
14-CH-0119 
PRINCIPAL INVESTIGATOR:  Jack Yanovski, M.D. 
 
 
STUDY TITLE: 
Pilot Study of the Effects of Colchicine in Non-Diabetic Adults with Metabolic Syndrome 
 
 
Continuing Review Approved by the IRB on 01/24/18 
Amendment Approved by the IRB on 07/13/18 (S)  
 
 
Date Posted to Web: 08/03/18 
Standard 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY 
 
•   Adult Patient or    •   Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent (1) 
 
 
INTRODUCTION 
 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
 
First, we want you to know that: 
 
 
Taking part in NIH research is entirely voluntary. 
 
 
You may choose not to take part, or you may withdraw from the study at any time.  In either case, you will not 
lose any benefits to which you are otherwise entitled.  However, to receive care at the NIH, you must be taking 
part in a study or be under evaluation for study participation. 
 
 
You may receive no benefit from taking part.  The research may give us knowledge that may help people in the 
future. 
 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research treatments 
they would want to receive (such as blood transfusions).  If you have such beliefs, please discuss them with your NIH 
doctors or research team before you agree to the study. 
 
Now we will describe this research study.  Before you decide to take part, please take as much time as you need to ask 
any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other 
health professional. 
 
 
Purpose of this Study 
 
Approximately 30% of adults in the US have a body mass index (BMI) over 30 kg/m2, and are at greater risk for a 
number of medical problems, including high blood pressure, high blood cholesterol, high triglyceride levels, high blood 
sugar (diabetes) and heart disease.  It is thought that being overweight leads to a state of low-level inflammation and 
this inflammation may actually lead to some of the medical problems associated with obesity.  The purpose of this study 
is to find out if a medication called colchicine can improve metabolism in adults who have medical complications of their 
high body weight (these complications are sometimes called the “metabolic syndrome”), but who have not yet developed 
high blood sugar (diabetes). 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  2  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Colchicine is an anti-inflammatory medication that has been used for centuries in the treatment of gout.  From animal 
studies and human studies there is some evidence that anti-inflammatory medicines like colchicine may improve the 
pancreas’s ability to secrete insulin and the body’s ability to regulate sugar.  We ask you to join our study, so we can find 
out whether colchicine can improve sugar regulation and metabolic parameters. 
 
If you qualify and agree to participate, you will be one of 40 people assigned by chance to take either colchicine or 
placebo capsules by mouth twice a day for 3 months.  The colchicine capsules will come in the same dose that is available 
in pharmacies and is prescribed for a disease called “gout”: 0.6 milligrams.  The placebo capsules look just like the 
colchicine capsules, but do not contain any colchicine.  You will have a 50% chance of being assigned to take colchicine.  
 
This study is designed to be ‘double-blind’: neither the doctors nor the study participants will know who is taking 
colchicine capsules and who is taking placebo.  Only the NIH pharmacy will know whether a study participant is receiving 
colchicine or placebo. Unless it becomes medically necessary, the participants and the doctors will not be told until the 
study is completed (when no participant is still taking colchicine). The purpose of the ‘double blinding’ is to make sure we 
avoid bias on the part of the people involved in the study.  When the study is completed, we will send all participants 
information about the results, and tell them whether they were taking colchicine or placebo capsules. 
 
Study participants will need to come to the NIH Clinical Center for four outpatient visits, with an optional fifth outpatient 
visit. It is important that participants arrive fasting (no food or beverages besides water) to each of these visits.  
Participants will be compensated for their time and inconvenience (see below: Compensation on page 5). 
 
Study Population 
 
We wish to recruit 40 overweight adults. 
 
Who Can Be in This Study 
 
You may be eligible for this research study if you are greater than 18 years old, have a body mass index that is at least 
30 kg/m2 (calculated by dividing weight in kg by height in meters squared), weigh less than 450 lbs, and are in good 
general health. You also have to meet certain levels for insulin resistance and inflammation, as measured by lab testing, 
to participate in the full study. If you are a woman of child-bearing age, you will be asked to use an effective form of 
birth control before participating in this study. 
 
Who May Not Be In This Study 
 
You may not be eligible for this study if you have a major medical illness that would interfere with study tests or 
measurements, such as heart, kidney, liver, lung, blood, gut, or endocrine diseases, or uncontrolled high blood 
pressure. If you are currently using a medication that affects sugar and fat metabolism or absorption in your body, or a 
medicine that should not be taken with colchicine, you may not be eligible to participate. Also individuals who are 
pregnant or nursing, or planning to become pregnant, have had a recent weight change greater than 3% of total body 
weight, have been using weight reducing medications, have recently used colchicine, have a known allergy to 
colchicine, or use tobacco or nicotine (e.g. e-cigarettes) products will not be recruited for this study. Individuals with a 
history of keloid formation (who easily develop scars on their skin after an injury) are advised not to take part in this 
study. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  3  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Procedures of the study 
 
The study consists of four outpatient visits: an outpatient screening visit at the Clinical Center to determine eligibility, 
a baseline visit to study your metabolism before the intervention, a short outpatient visit to check how you are 
feeling, and a final visit 3 months after the baseline visit look for changes after the intervention.  Upon completing the 
final visit, you have the option to return 3 months later to come for another washout visit. This visit will look to see if 
the changes from the intervention continue to last even after stopping the study medication.  You will be randomized to 
receive colchicine or placebo on the day you complete the baseline visit. 
 
Outpatient Screening Visit 
 
This visit will take about 3 hours to complete.  You will be seen on a weekday in the Clinical Center at the National 
Institutes of Health.  We ask that you remain fasting for 10 hours before coming to the clinic and have nothing to eat or 
drink except water that morning.  During this visit, we will perform the following: 
 
1. Protocol review and signing of consent form. We will go over the study in detail, and answer any questions. 
The consent form will need to be signed before you can take part in the study. 
 
2. Complete medical history and physical exam, with weight, height, and blood pressure measurement. 
 
3. An EKG will be performed to examine your heart function. 
 
4. Fasting blood tests to ensure that you are in good health. The analysis will examine blood cell count, liver and 
kidney function, cholesterol levels, blood sugar and insulin levels, thyroid tests, inflammation level, as well as 
reserve blood samples to be preserved for additional possible research tests.  We will also plan to do tests to find 
out if you have any differences in genes that may be important for metabolism and body weight. In addition to 
looking at some genes we already think are important for body weight, we will use new DNA sequencing 
technology that will look at all the human genes we know about. This is known as exome and genome 
sequencing. This new technology allows us to look at DNA in great detail. 
 
5. Urine sample collection to ensure that your kidneys work normally, that you are not taking any illicit drugs, 
and a pregnancy test (for women of childbearing age). 
 
6. Oral glucose tolerance test.  We will perform a test to examine whether you have diabetes, called a 2-hour 
glucose tolerance test.  You will drink a cup of sugar water and then will have your blood drawn 1 and 2 hours 
later to look at your blood sugar level. 
 
7. Dual energy x-ray absorptiometry (DEXA) to look at your body composition. The test involves lying still on a 
table while a small camera passes over your body. The dose of the x-ray is much less than the amount you would 
get from a normal chest x-ray. The total amount of time to do this test will be about 20-30 minutes. 
 
 
 
Baseline Visit 
 
If you qualify for participation in the study, you will be scheduled for the baseline visit.  We ask that you remain fasting 
for 10 hours before coming to the clinic and have nothing to eat or drink except water that morning.  You will be seen on 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  4  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
a weekday in the Clinical Center at the National Institutes of Health, and the visit will take about 8 hours to complete.  
During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement.  A 
questionnaire will also be performed. 
 
2. Fasting blood tests to look at your baseline metabolic and inflammatory levels, as well as reserve blood 
samples to be preserved for additional possible research tests including a sample for future genetic analysis.  We 
will insert a small needle into your vein (an intravenous line or I.V.) in order to obtain blood samples. 
 
3. Stool sample collection. We will obtain two stool samples to save for future experiments.  As part of this 
collection, we will ask you to keep track of your diet for 24 hours on a form that will be provided to you, as diet 
can affect the results of the stool testing.  You will also go over this “food record” in person with a nutritionist. 
 
4. Urine sample collection as described before. We will also collect urine over your eight hours of testing to save 
for future experiments. 
 
5. Frequently sampled intravenous glucose tolerance test (FSIVGTT).  This study tells us a lot about how 
sugar is used by your body, how well your insulin works, and how sensitive your body is to insulin.  The FSIVGTT 
study is done while you rest in bed.  A second IV line will be placed in your arm. We will give you some sugar 
water into one IV over a 2 minute period.  We will then draw blood samples from the other IV at -15, -10, -5, -1, 
2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 25, 30, 40, 50, 70, 100, 140, and 180 minutes (a total of 3 hours) to measure 
sugar and insulin levels.  Exactly 20 minutes into the test, we will give you a small amount of insulin through the 
IV.  A physician or nurse practitioner will be present during the first hour of the study. You can watch TV during 
this test. 
 
6. Computed Tomography (CT) Scan of the abdomen to look at where you tend to store your fat.  The test 
involves lying still on a movable table which passes through a large ring where the camera sits.  The test does 
involve radiation, but because we only need to take a snapshot of your abdomen, the method that will be used 
minimizes your exposure.  The total amount of time to do this test will be about 20-30 minutes. 
  
7. Subcutaneous Fat Biopsy. To examine the level of certain molecules in your fat tissue, a small sample of fat 
tissue will be taken from under the skin of your abdomen via a “mini-liposuction” technique. Lidocaine, a local 
anesthetic, is used to numb the area.  A needle will be used to remove a piece of fat tissue measuring about 1 ½ 
teaspoons.  A bandage is then applied to the site of needle insertion.  We can give you some mild pain 
medication such as Tylenol, or stronger medication if needed, after the biopsy. The biopsy will be taken from a 
place on your body that is normally covered and not easily seen.  
 
8. Dispense Study Medication. You will be given approximately an 8-week supply of study medication to be 
taken two times a day (morning and late afternoon/evening) at home. The medication can be taken with or 
without food. We will give you a reminder alarm to help you remember when to take your medicine. If you forget 
to take a dose, then take it as soon as you remember.  But if it is within 4 hours of the time for your next dose, 
do not take a double dose.  Just skip the missed dose.  
 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  5  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Short Outpatient Visit 
 
To make sure that you doing well taking the medication, you will be seen on a weekday in the Clinical Center at the 
National Institutes of Health. This visit will take about 2 hours to complete.  We ask that you bring your bottle of pills 
with you. During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement. 
  
2. Fasting blood tests to ensure that you are in good health, to examine your inflammation levels, as well as 
reserve blood samples to be preserved for additional possible research tests. 
 
3. Urine sample collection as described before. 
 
4. Dispense Study Medication.  We will give you another bottle of study medication (about 8 weeks’ worth) to 
last you until the Final (3 month) Visit.  As before, if you forget to take a dose, then take it as soon as you 
remember.  But if it is within 4 hours of the time for your next dose, do not take a double dose.  Just skip the 
missed dose. 
 
Final Visit 
 
We will ask you to bring your bottle with any leftover pills to your final visit appointment.  We ask that you remain fasting 
for 10 hours before coming to the clinic and have nothing to eat or drink except water that morning.  You will be seen on 
a weekday in the Clinical Center at the National Institutes of Health, and the visit will take about 8 hours to complete.  
During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement.   
2. Fasting blood tests as described before. We will insert a small needle into your vein (an intravenous line or 
I.V.) in order to obtain blood samples. 
3. Stool sample collection as described before. 
4. Urine sample collection as described before. 
5. Frequently sampled intravenous glucose tolerance test (FSIVGTT) as described before.  
6. DEXA Scan as described before. 
7. CT Scan as described before. 
8. Subcutaneous Fat Biopsy as described before 
9. Exit questionnaire to tell us about your experience of participating in our protocol. 
 
Optional Washout Visit 
 
Because we would like to see if colchicine will continue to have lasting positive effects on your glucose regulation, 
metabolism, inflammation, and/or cardiovascular health even after you’ve stopped taking it, we invite patients to return to 
the NIH Clinical Center 3 months after finishing the study medication for repeat testing.   
 
As before, we ask that you remain fasting for 10 hours before coming to the clinic and have nothing to eat or drink 
except water that morning.  You will be seen on a weekday in the Clinical Center at the National Institutes of Health, and 
the visit will take about 8 hours to complete.  During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement.   


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  6  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
2. Fasting blood tests as described before. We will insert a small needle into your vein (an intravenous line or 
I.V.) in order to obtain blood samples. 
3. Stool sample collection as described before. 
4. Urine sample collection as described before.   
5. Frequently sampled intravenous glucose tolerance test (FSIVGTT) as described before.  
6. DEXA Scan as described before. 
7. CT Scan as described before. 
8. Subcutaneous Fat Biopsy as described before 
 
When the study is complete, you will return to the care of your regular physician. Participation in this study does not 
commit NIH to your long term care. 
 
Results of Tests at the NIH 
 
We will be measuring many things in your blood during your visits, and it is possible we might uncover a medical problem 
that requires treatment.  You will not be routinely provided treatment for any health condition discovered. However, you 
will be informed about such findings (e.g., high blood pressure) and any medically important information including blood 
tests or physical exam results will be forwarded to your primary care physician at your request.  Some of these medical 
problems might prevent you from participating further in the study. 
 
Risks and discomforts 
 
1. Physical examination. A physician or a nurse practitioner may need to examine you with your clothes off, with 
appropriate precautions to protect your privacy.  Some may find this examination embarrassing. 
 
2. Radiation Exposure: This research study involves exposure to radiation from three DEXA scans and three CT 
scans. Please note that this radiation exposure is not necessary for your medical care and is for research 
purposes only.   The NIH Radiation Safety Committee has reviewed the use of radiation in this research study and 
has approved this use as involving minimal risk and necessary to obtain the research information desired. 
 
Although each organ will receive a different dose, the amount of radiation exposure you will receive yearly from 
this study is equal to a uniform whole-body exposure of 0.093 rem. This calculated value is known as the 
“effective dose” and is used to relate the dose received by each organ to a single value. The amount of radiation 
you will receive in this study is below the dose guideline established by the NIH Radiation Safety Committee for 
research subjects.  This guideline is an effective dose of 5 rem received per year. 
 
For comparison, the average person in the United States receives a radiation exposure of 0.3 rem per year from 
natural background sources, such as from the sun, outer space, and from radioactive materials that are found 
naturally in the earth’s air and soil.  If you would like more information about radiation and examples of exposure 
levels form the other sources, please ask the investigator for a copy of the pamphlet called, An Introduction to 
Radiation for NIH Research Subjects. 
 
3. Blood withdrawal.  The blood withdrawal amount is well below the NIH guideline for a safe amount of blood 
withdrawal (550 cc every 8 weeks).  A small bruise may form at any site where the blood is taken.  The risk of 
infection or fainting is very small.  Inflammation or clotting of a vein also may rarely occur. 
 
Some of your blood will be sent to another laboratory within the NIH to examine your inflammation levels.  The 
samples will be coded, and only the investigators from this study will have access to the identity of the samples. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  7  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
4. Stool sample collection has no risk, and should only take a moment to complete.  The samples will be coded, 
and only the investigators from this study will have access to the identity of the samples. 
 
5. Urine sample collection has no risk and should only take a moment to complete.  If you do test positive for an 
illicit substance, the result will be part of your NIH Medical Record. 
 
6.  Questionnaires are not risky, but may be inconvenient because of the time necessary to complete them. 
 
7.  Oral glucose tolerance test.  This test is inconvenient because of the time it takes to complete.  The only risks 
from this kind of study are those described for any blood draw, as well as developing nausea from the oral 
glucose. Patients may transiently develop high blood sugar levels from the glucose, but it should normalize within 
a few hours and should not be clinically significant. 
 
8. Intravenous glucose tolerance test. This test is inconvenient because of the time it takes to complete.  You 
can watch TV during this test. The only risks from these kinds of studies are those described for any blood draw, 
the possibility of slight arm tenderness in the arm receiving the sugar infusion, (this tenderness goes away within 
a few minutes with gentle rubbing of the arm), and the possibility of a low blood sugar during the study.  With 
slightly low blood sugars (less than 50 mg/dL), participants may get hungry, have a headache, feel shaky or 
dizzy, may become drowsy, or may become sweaty.  With very low blood sugars (under 30 mg/dL) participants 
may have trouble speaking, be difficult to arouse, and even have seizures.  However, in the test we are doing, we 
will be giving you extra sugar to raise your blood sugar above normal, and then we will try to bring it back to 
normal (95-105 mg/dL) with insulin.  To do this, we will measure blood sugar at 2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 
24, 27, 30, 40, 50, 70, 90, 120, 140, 160, and 180 minutes (a total of 3 hours).  A physician or nurse practitioner 
will be present during the first hour of your test to make sure everything is working properly.  We expect that the 
chance of even a slightly low blood sugar is very low.  If a low blood sugar does not come up on its own quickly, 
the test will be stopped and you will be given sugar by vein to raise the blood sugar to normal. 
 
9. Fat tissue biopsies. Possible side effects of the biopsy procedure are pain during and for two to three days 
after the procedure, although rarely the biopsy site may be tender or sore or have bruising or swelling for 2-3 
weeks. Biopsy wounds usually heal with a very small, nearly unnoticeable scar, but sometimes a raised scar 
(keloid) or visible lump may result. Your risk is slightly higher if you are African American. Lidocaine injection for 
numbing before fat biopsies may cause some mild burning before the numbing takes effect. Rare adverse effects 
include infection at the biopsy sites or an allergic reaction to Lidocaine that may lead to a rash and/or swelling of 
the injected area. If you know you are allergic to Lidocaine, we will change to another local anesthetic. Another 
risk of the procedure is minor bleeding in the area of the biopsy. Some medications may increase the amount of 
bleeding from the biopsy. If you are taking medications such as Coumadin, Plavix or aspirin to thin your blood, 
you WILL NOT have a biopsy. If you are taking aspirin or non-steroidal medications such as Advil for pain you will 
need to stop taking these medicines for one week before the biopsy is performed. 
 
10. Medication.  The most common adverse effects from the medication used in this study are nausea, vomiting, 
diarrhea, and abdominal pain.  Some rare side effects (< 1%) have been reported including decreased production 
of red cells (which could make you feel tired), white blood cells (which can make more susceptible to infections), 
and/or platelets (which may make you more susceptible to bruising or bleeding), tingling (neuropathy), dizziness, 
muscle pain or weakness, rash, allergic reaction, decreased sperm count, and increased liver enzyme levels.  
These symptoms usually occur in people with underlying medical problems, or were on certain medications, that 
predisposed them to having the reaction.  In general, these symptoms resolved within a week once the 
medication was stopped. Although colchicine has been used for about 2000 years for gout, as with any 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
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CONTINUATION:  page  8  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
medication, there is always the possibility of unpredicted side effects.  We will monitor you for all adverse effects.  
If (severe) adverse effects develop, we will decrease the dose, temporarily stop, or discontinue the medication.   
 
If you experience any of the following, contact our team right away: 
• 
Muscle weakness or pain 
• 
Numbness or tingling in the fingers or toes 
• 
Unusual bleeding or bruising 
• 
Severe diarrhea or vomiting 
 
There are no adequate well-controlled studies on the use of colchicine in pregnancy.  Data from a limited number 
of published studies found no evidence of an increased risk of miscarriage, stillbirth, or teratogenic effects among 
pregnant women using colchicine.  However, colchicine did demonstrate birth defects in the offspring of pregnant 
rats.  If you think you might become pregnant, we will ask that you not participate in this study. 
 
• 
Taking certain medicines with colchicine can cause your level of colchicine to be too high, especially if 
you have kidney or liver problems (refer to “Medication Guide” for more information).   
• 
Even medicines that you take for a short period of time, such as antibiotics, can interact with colchicine 
and cause serious side effects or death.  Please tell us about any new medicine you need to take so we 
can make sure you can continue using colchicine.  
• 
Avoid drinking grapefruit juice, as it can interfere with your body’s ability to breakdown colchicine. 
 
Keep the medication out of the reach of children. 
 
11. DNA testing. If you allow us to study your DNA, we will use it for genome sequencing. Genome sequencing is a 
test that could give us different kinds of results. These include: 
a. We could identify changes in genes that are related to metabolism and body weight. 
b. We could identify changes in genes that contribute to other diseases or problems.  
c. We could identify changes in genes that are not known to cause any disease. These are known as normal 
variations.  
d. We could find changes in genes that are new and of uncertain clinical importance. This means that we do not 
know if they could cause or contribute to a disease or if they are normal variations. 
 
Not all gene changes will have health implications for your family. Changes in genes that have health implications 
for your family: 
 
1. May have already caused health problems. 
2. May cause a health problem in the future. 
 
One of the goals of this study is to identify changes in genes that may be involved in obesity. This research may 
take years. If however we identify a genetic cause or likely cause of obesity, with your permission, we will contact 
you. Please let us know your preference by initialing one of these two statements: 
 
______  I would like to be contacted with information about the progress of this study and contacted 
about any results related to obesity. I understand that this research will take years and that a 
specific abnormality might not be identified in me. 
 
______ Please do not contact me regarding the progress of this study or any specific gene changes 
related to obesity. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  9  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
If we detect a genetic change that might be important for you, then we will have to confirm this result in a 
certified laboratory. For this confirmation, we will ask for a new sample of DNA from you. In most cases this will 
involve obtaining a small sample of blood (1-2 teaspoons). In some cases we can obtain enough DNA to confirm 
a genetic change by swabbing the inside of the cheek. You can decide whether you want to do that later, if we 
contact you with the information that we have found a possible important genetic difference. 
 
Identifying gene changes that are not related to the condition being studied is known as incidental medical 
information. 
 
We will find gene changes in everyone that we study, but we are only specifically looking for genes related to 
metabolism and body weight. We will not analyze your DNA for changes that are not related to metabolism and 
body weight. Even so, some gene changes not related to metabolism and body weight will be detected.  
 
We will only inform you only of changes that have urgent medical significance and would benefit from early 
medical treatment. An example of this would be a gene change that causes cancer and where you would benefit 
from early screening. We will not inform you of all gene changes that have uncertain health implications. For 
example we will not report gene changes that only predispose individuals to disease. An example of this would be 
a gene change that influences the risk of heart disease, but where the development of the disease is dependent 
on many genetic and non-genetic (such as diet and smoking) factors. If we find a change in a gene that is 
important to your family’s health, we will only be able to give you those results if the change has been confirmed 
in a certified laboratory. To make sure an error has not occurred, we would need to obtain a new sample of DNA 
from you to confirm the experimental results.  
 
In addition to knowing what we could find, we would like you to know the limitations of the genome sequencing 
and what we will NOT be able to tell you about the changes that we find.  
 
1. Not all gene changes that cause disease will be detected.  
2. Some changes that are not currently known to cause health problems will be found to cause health problems 
in the future. We cannot promise to be able to tell you about those changes in the future.  
3. We will not tell you about gene changes that are not known to have health implications, nor will we tell you 
about gene changes that have only reproductive consequences.  
4. This gene sequencing cannot be substituted for diagnostic testing recommended by another physician.  
 
Please initial all of the following statements to indicate that you understand the extent to which we will inform 
you about incidental genetic changes that we find:  
 
______ I understand that I will be informed only of genetic changes that researchers involved in this 
study feel are urgently important for my family’s health and that knowledge of these changes has 
the potential to provide a significant benefit for me or my family.  
 
______ I understand that investigators will not specifically look for gene changes not related to 
metabolism and body weight, and that identification of other disease-causing genes will only 
occur by chance depending on the analysis being done.  
 
______ I fully understand that even though they could have health or reproductive consequences, I will 
not be told about all genetic changes identified that are not related to metabolism and body 
weight.  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  10  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
If we detect a gene change not related to metabolism and body weight and the investigators feel it meets the 
requirements of having urgent medical significance so that you would benefit from medical treatment, then you 
will be given a choice to learn or not learn about a genetic change that we find. You can chose not to be 
contacted at all if that is your preference. An exception to your ability to choose whether or not to find out about 
a gene change would be a gene change that investigators feel is of critical importance to your health. An example 
of this would be a gene change that has a high probability of causing cancer or a disease for which early 
treatment would be beneficial. Before confirming the result in a clinical laboratory we will contact you to obtain a 
new sample of DNA. 
 
If you have a gene change with urgent health implications, the NIH will confirm the genetic change present in 
one member of your family. We will discuss the results with you so that you understand who else in your family 
could be a carrier for this same change. We can help arrange for this testing to be done, but the NIH cannot 
promise to perform or pay for the clinical testing necessary to confirm or determine who else in your family may 
have this change in their DNA. 
 
Once a gene change is confirmed, we will discuss the results with you and make recommendations regarding 
appropriate medical follow up. The NIH cannot promise to perform or pay for recommended medical tests or 
evaluations. 
 
It is possible that a gene change will not be confirmed on subsequent testing. This could be due to an error in the 
DNA sequencing or an error in processing the DNA or cell lines. Although you likely will be glad that we did not 
confirm a problem, this may cause some anxiety and concern that you otherwise would not have experienced. 
 
Please let us know your preferences by initialing one of the following statements: 
 
______ I DO want to be re-contacted if genetic variants with urgent health implications are discovered 
during this research testing. 
 
______ I DO NOT want to be re-contacted if genetic variants with urgent health implications are 
discovered during this research testing. I understand that an exception to this choice, as 
described above, will be made for a gene change of critical medical significance. 
 
Emotional and psychological risks from DNA testing. Identification of gene changes could cause emotional 
and psychological problems. In some situations psychological counseling could be recommended. 
 
1. Learning about disease risk in your family can be distressing. 
2. Learning that you passed on a gene that does not work to your child can be distressing. 
3. Other members of your family could be upset to learn that they may be at risk for a disorder because of your 
participation in this study. 
 
You may be falsely reassured about your health status if we do not report any changes to you. 
 
Other risks of genetic testing. If we confirm a gene change in your DNA in a diagnostic laboratory, this 
information will become part of your medical record at the NIH. Some people are concerned that information 
about them from their medical records could be released. Possible problems include insurance or employment 
discrimination. Measures to protect the confidentiality of your information are described below. These problems 
may also occur if you disclose information yourself or agree to have your research records released. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  11  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
There are state and federal laws that protect against genetic discrimination. A federal law called the Genetic 
Information Nondiscrimination Act (GINA) generally makes it illegal for health insurance companies, group health 
plans, and most employers to discriminate against you based on your genetic information. According to this law, 
health insurance companies or group health plans (as of May 21, 2010) cannot request your genetic information 
or use it to make decisions about your eligibility or premiums; and employers cannot use it in deciding to hire, 
promote, or fire you or in setting the terms of your employment (as of Nov 21, 2009). 
 
Be aware that this Federal law does not protect you against genetic discrimination by companies that sell life 
insurance, disability insurance, or long-term care insurance. 
 
The following link contains details on this policy: 
http://www.genome.gov/Pages/PolicyEthics/GeneticDiscrimination/GINAInfoDoc.pdf 
 
You may ask your research team for additional information or a copy of The Genetic Information 
Nondiscrimination Act of 2008 informational document. 
 
Genetic studies can uncover unexpected family relationships. For example, it is possible that we might learn that 
a family member is not the biological child of the parents with whom she or he lives (for example, because of 
adoption). We will not ordinarily provide this type of information to any member of the family or to the referring 
physician. However, we may make exceptions under extraordinary circumstances if this information were required 
for the medical care of the individuals involved. If we are convinced this is necessary, we will provide the 
information to the physician providing medical care to the patient. 
 
Use of stored samples and data 
 
Future DNA Research. Currently we plan to sequence known genes. This represents only about 1% of your 
DNA sequence. In the future we may sequence other parts of your DNA, and eventually, we may completely 
sequence your DNA. These additional studies may occur years from now. Some of your DNA may be sent to other 
laboratories for specific tests. If this is done DNA will be coded and not have your name on the sample or the 
paperwork that goes to the laboratory. Should you withdraw from this study, we will keep your DNA for analysis 
unless you ask us to destroy the DNA samples. 
 
Please initial one of the following three statements regarding future research: 
 
______  DNA can be used for other kinds of future health-related research. This research is not limited to studies 
related to obesity, metabolism and body weight. This testing may be done by research laboratories that 
are not at the NIH. I authorize use of these samples without my additional consent. I understand I will 
not be contacted if these samples are used in the future. 
 
______  I understand that genetic samples collected during these NIH visits will be saved and used for future 
experimental testing related to obesity, metabolism, and body weight. This testing may be done by 
research laboratories that are not at the NIH. I do NOT authorize use of these samples for any other 
purpose without my additional consent. I must be contacted and give consent if these samples are to be 
used in the future. 
______ Do not use my DNA for any future studies beyond those described above in this consent form. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  12  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Future research with blood samples. Our specific research plans have been summarized in this consent form. 
In the course of the research, we will obtain blood samples. While we can do some of our tests immediately, we 
may want to store your blood samples in the freezer for future studies. In addition, certain information will be 
stored in your medical record. In the future, it is possible that your blood samples or medical records will be used 
for other research purposes that are not specifically outlined in this consent form. If this is done, samples will be 
coded, and you will not be identified by name. These samples may be stored at a separate site (called a 
repository) that specializes in storing clinical samples. You have the option, in the future, of requesting that these 
samples not be used for any additional testing. In addition, it is possible that some information obtained from 
these studies will be published in the medical literature. However, your identity will not be included in any 
publications. 
Please initial one of the following two statements: 
 
______ I understand that samples collected during these NIH visits will be saved and used for future 
experimental testing related to body weight, and/or metabolism. This testing may be done by research 
laboratories that are not at the NIH. I authorize other uses of these samples without my additional 
consent. I understand I will not be contacted if these samples are used in the future. 
 
______ I understand that samples collected during these NIH visits will be saved and used for future 
experimental testing related to body weight, and/or metabolism. This testing may be done by research 
laboratories that are not at the NIH. I do NOT authorize any other use of these samples without my 
additional consent. I must be contacted and give consent if these samples are to be used in the future. 
 
All through the process of the study and afterwards, the confidentiality of participants will be protected by using 
codes and medical record numbers in recording your information and test results. Only medical personnel 
involved in this study will have access to participants’ names, test results, and patient code numbers. 
 
You need to be aware that DNA sequence is like a fingerprint. Theoretically if enough DNA sequence information 
is available, someone could identify you based on his/her DNA sequence. To facilitate genetic research, your DNA 
sequence information may be deposited in other databases. In this case, unless we have your permission, we will 
deposit the data in a manner that would not allow someone to identify you. Please understand that this 
information cannot be removed once it is deposited. 
 
Please initial one of the following boxes. 
 
______ I do not want DNA sequence data to be deposited in any database other than the one associated with 
this study. 
 
______ My DNA sequence data can be deposited in databases that limit access to IRB (ethics board) approved- 
researchers. 
 
______ My DNA sequence can be deposited in a database that is available only to scientists but that does not 
require IRB approval of research studies. I understand that someone could theoretically identify me from 
this information. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  13  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Potential benefits of participation 
 
We are hopeful that your participation in this study will provide evidence as to whether colchicine will help metabolic 
parameters in obese individuals.  However, you might not benefit directly from participating in this study.  Should we find 
abnormalities in any of your test results, you will be notified and receive a copy to assist you in seeking further medical 
evaluation. This information may or may not improve your health.  
 
 
Right of Withdrawal and Conditions for Early Withdrawal  
 
You may withdraw from the study at any time and for any reason without loss of benefits or privileges to which you are 
otherwise entitled.  
 
 
Discussion of New Findings with You 
 
After all participants have completed the study, we will inform you about which medicine you took and, once the study is 
fully analyzed, let you know if colchicine seemed to help with inflammation and insulin resistance. There is no general 
plan to share your individual test results with you. However, if any findings suggest you have a medical issue, we will 
provide this information to you and your primary care provider. You may request a copy of your routine laboratory tests if 
you desire.  
 
 
Study Termination 
 
You may be asked to end your participation in this study at any time if we believe that continuation is not in your best 
medical interest or if you are unable to comply with the requirements of the study.  
 
 
Alternatives to Participation 
 
The alternative to this study is not to participate. You may be eligible for other studies in the NIH. You may learn more 
about them through www.clinicaltrials.gov. 
 
 
Compensation 
You will be compensated for the time and inconvenience associated with participation according to NIH research 
volunteer guidelines.  Compensation for completing all of the testing described above is $100 for the outpatient screening 
visit, $50 for the safety visit, and $300 each for the baseline, final, and washout visits.  The total amount you could 
receive for participation if you complete all parts of this study is $1050. 
 
 
Conflict of Interest 
 
The NIH and members of this research team have no financial interest related to this research study.  
 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  14  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
Posting of Research Results on www.ClinicalTrials.gov  
 
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This web site 
will not include information that can identify you. At most the Web site will include a summary of the results. You can 
search this Web site at any time. 
 
 
______  I have received a copy of the signed consent form. 
 


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  15  of  15  pages 
 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
OTHER PERTINENT INFORMATION 
 
1. Confidentiality.  When results of an NIH research study are reported in medical journals or at scientific meetings, the 
people who take part are not named and identified.  In most cases, the NIH will not release any information about your 
research involvement without your written permission.  However, if you sign a release of information form, for example, 
for an insurance company, the NIH will give the insurance company information from your medical record.  This information 
might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance. 
 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you should know that the Act 
allows release of some information from your medical record without your permission, for example, if it is required by the 
Food and Drug Administration (FDA), members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
 
2. Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-term medical care for any 
injury resulting from your participation in research here.  In general, no long-term medical care or financial compensation 
for research-related injuries will be provided by the National Institutes of Health, the Clinical Center, or the Federal 
Government.  However, you have the right to pursue legal remedy if you believe that your injury justifies such action. 
 
3. Payments.  The amount of payment to research volunteers is guided by the National Institutes of Health policies.  In 
general, patients are not paid for taking part in research studies at the National Institutes of Health.  Reimbursement of 
travel and subsistence will be offered consistent with NIH guidelines. 
 
4. Problems or Questions.  If you have any problems or questions about this study, or about your rights as a 
research participant, or about any research-related injury, contact the Principal Investigator, Jack A. Yanovski, MD, PhD; 
Building 10-CRC Room 1-3330, Telephone: 301-496-4686 or Associate Investigator Andrew Demidowich, MD; Building 10-
CRC Room 1-3330, Telephone: 301-496-4686. 
 
You may also call the Clinical Center Patient Representative at 301-496-2626. 
 
5. Consent Document.  Please keep a copy of this document in case you want to read it again. 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby consent to take 
part in this study. 
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby give permission 
for my child to take part in this study.   
(Attach NIH 2514-2, Minor’s Assent, if applicable.) 
 
  
 
 
  
 
Signature of Adult Patient/Legal Representative 
Date 
 
 
 
Print Name 
Signature of Parent(s)/Guardian 
Date 
 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to participate in the study. 
 
 
 
  
 
 
 
 
Signature of Parent(s)/Guardian 
Date 
 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM JANUARY 24, 2018 THROUGH FEBRUARY 24, 2019. 
 
 
 
  
 
 
  
 
Signature of Investigator 
Date 
 
 
 
Print Name 
Signature of Witness 
Date 
 
 
 
Print Name 
 


 
 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
               • Adult Patient or     •  Parent, for Minor Patient 
 
 
INSTITUTE: 
Instituto Nacional de Salud Infantil y Desarrollo Humano (National Institute of Child Health and  
 
Human Development) 
 
 
STUDY NUMBER: 
14-CH-0119 
PRINCIPAL INVESTIGATOR:  Jack Yanovski, M.D. 
 
 
STUDY TITLE: 
Estudio preliminario de los efectos de la colchicina en adultos no diabéticos con síndrome 
metabólico 
  
(Pilot Study of the Effects of Colchicine in Non-Diabetic Adults with Metabolic Syndrome) 
 
 
Continuing Review Approved by the IRB on 01/24/18 
Amendment Approved by the IRB on 07/13/18 (S)  
 
 
Date Posted to Web: 08/03/18 
Standard Spanish 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY 
 
•   Adult Patient or    •   Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent (2) 
 
 
INTRODUCCIÓN 
 
Deseamos invitarle a participar en un estudio de investigación en los Institutos Nacionales de Salud (National Institutes of 
Health, NIH). 
 
En primer lugar, queremos que Ud. sepa que: 
La participación en una investigación del NIH es totalmente voluntaria. 
Usted puede decidir no participar o retirarse del estudio en cualquier momento. En cualquier caso, no perderá 
ninguna compensación a la que pueda tener derecho. No obstante, para recibir atención médica en el NIH usted 
debe participar en un estudio o estar en evaluación para participar en uno. 
 
Es posible que no reciba ningún beneficio por su participación. Con la investigación podemos adquirir 
conocimientos que ayuden a otras personas en el futuro. 
 
En segundo lugar, algunas personas pueden tener creencias personales, religiosas o éticas que limiten los tipos de 
tratamientos médicos o de investigación que deseen recibir (por ejemplo, transfusiones de sangre). Si usted es una de 
esas personas, hable al respecto con sus médicos o con el equipo de investigación del NIH antes de acceder a participar 
en el estudio. 
 
El estudio se describe en las siguientes páginas. Antes de decidir participar, tómese todo el tiempo que necesite para 
hacer preguntas y hablar del estudio con cualquier persona del NIH, o con su familia, amigos, médico personal o 
cualquier otro profesional de la salud.
 
Propósito de este Estudio 
Aproximadamente 30% de los adultos en los EE.UU. tienen un índice de masa corporal (IMC ) superior a 30 (kg /m2), y 
están en mayor riesgo de una serie de problemas médicos, incluyendo la presión arterial alta, colesterol alto en la sangre, 
niveles altos de triglicéridos, azúcar en la sangre (diabetes) y enfermedades del corazón. Se cree que tener sobrepeso, 
puede llevar a un estado de inflamación aunque de nivel bajo, y que esta inflamación puede conducir a algunos de los 
problemas médicos asociados con la obesidad. El propósito de este estudio es investigar si un medicamento llamado 
colchicine puede mejorar el metabolismo de los adultos que tienen complicaciones médicas debido a su sobrepeso 
corporal (estas complicaciones son algunas veces llamadas, "síndrome metabólico"), pero que aún no han desarrollado 
altos niveles de azúcar en la sangre (diabetes). 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  2  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Colchicine es una medicación anti- inflamatoria que se ha utilizado durante siglos en el tratamiento de la gota. A partir de 
estudios en animales y estudios en humanos, existe alguna evidencia de que los medicamentos anti-inflamatorios 
como colchicine pueden mejorar la capacidad del páncreas para secretar insulina y la capacidad del cuerpo para regular el 
azúcar. Les pedimos que se unan a nuestro estudio, por el cual esperamos averiguar si colchicine puede mejorar la 
regulación del azúcar y los parámetros metabólicos. 
  
Si califica y está de acuerdo en participar, Ud. será una de 40 personas asignadas al azar para tomar ya sea cápsulas de 
colchicine o cápsulas de placebo por vía oral, dos veces al día durante 3 meses. Las cápsulas de colchicine vendrán en la 
misma dosis que está disponible en las farmacias y se prescribe para una enfermedad llamada "gota": 0.6 miligramos. Las 
cápsulas de placebo se parecen a las cápsulas colchicine, pero no contienen colchicine. Usted tendrá un 50% de 
probabilidad de ser asignado a tomar colchicine. 
  
Este estudio está diseñado para ser "doble ciego": ni los médicos ni los participantes del estudio sabrán quién está 
tomando las cápsulas de colchicine y quién está tomando placebo. Sólo la farmacia del NIH sabrá si un participante en el 
estudio está recibiendo colchicine o placebo. A menos que sea necesario por razones médicas, ni los participantes ni los 
médicos serán informados de quién esta tomando lo uno o lo otro, hasta que se complete el estudio (hasta cuando todos 
los participantes terminen de tomar las capsulas). El propósito del estudio "doble ciego" es asegurarse de que no va a 
existir prejudicio hacia ninguna de las personas involucradas en el estudio. Cuando se haya completado el estudio, le 
enviaremos cada uno de los participantes información sobre los resultados y les daremos a conocer si estaban tomando 
colchicine o cápsulas de placebo. 
   
Los participantes del estudio tendrán que venir al Centro Clínico del NIH para cuatro consultas ambulatorias, con una 
quinta consulta ambulatoria opcional. Es importante que los participantes llegen en ayunas (sin alimentos ni bebidas 
aparte de agua) a cada una de estas visitas. Los participantes serán compensados por su tiempo y cualquier 
inconveniente (ver más abajo: Compensación en la página 5). 
 
Población de estudio 
Deseamos reclutar a 40 adultos con sobrepeso. 
  
Quién puede participar en este estudio 
Usted puede ser elegible para este estudio de investigación si es mayor de 18 años de edad; si tiene un índice de masa 
corporal mínimo de 30, el cual se calcula dividiendo el peso del individuo en kilogramos, por su altura en metros, al 
cuadrado, (Kg/m2); pesar menos de 450 libras, y que se encuentre en buen estado de salud general. Usted también tiene 
que cumplir con ciertos niveles de resistencia a la insulina y a la inflamación, medidas por pruebas de laboratorio, para 
participar en todo el estudio. Si usted es una mujer en edad de procrear, se le pedirá que use un método efectivo de 
control de la natalidad antes de participar en este studio. 
 
Quienes no pueden participar en este estudio 
Usted no puede ser elegible para este estudio si tiene una enfermedad médica grave que pudiera interferir con las 
pruebas o mediciones del estudio, como enfermedades del corazón, riñón, hígado, pulmón, sangre, intestinal o 
enfermedades endocrinas o presión arterial alta no controlada. Si usted está usando un medicamento que afecta 
el metabolismo del azúcar y la grasa o la absorción en su cuerpo, o un medicamento que no se debe tomar con  
colchicine, es posible que no sea elegible para participar. Tampoco son elegibles las mujeres que están embarazadas o 
lactando, o tienen intención de quedar embarazadas; las personas que han tenido un cambio de peso reciente superior al 


 
  
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3% del peso corporal total, han estado utilizando medicamentos para reducir el peso, han usado recientemente la 
colchicina, tener una alergia conocida a la colchicina, o utilizan productos de tabaco o nicotina (p. ej. e-cigarrillos), no 
serán reclutadas para este estudio. Se recomienda a las personas con antecedentes de formación de queloides (que  
fácilmente desarrollan cicatrices en su piel después de una lesión) no participar en este estudio. 
  
Procedimientos del estudio 
  
El estudio consta de cuatro visitas ambulatorias en el Centro Clínico: una visita para determinar elegibilidad, una 
visita inicial para estudiar su metabolismo antes de la participación, una corta visita ambulatoria para comprobar 
cómo se siente el participante durante el estudio, y una visita final 3 meses después de la visita inicial para ver los 
cambios después de la participación. Al término de la visita final, usted tiene la opción de volver 3 meses después para 
otra visita en la cual se quiere ver si los cambios observados mientras la participacion en el estudiopermanecen incluso 
después de suspender la medicación del estudio. Se le asignará al azar para recibir la colchicina o placebo el día de 
completar la visita inicial. 
 
Visita Ambulatoria de Selección de Pacientes  
  
Esta visita tomará unas 3 horas para realizarse. Usted será visto en un día de semana en el Centro Clínico del NIH. Le 
pedimos permanecer en ayunas durante las 10 horas anteriores a su llegada a la clínica y no debe comer o beber nada, 
excepto agua por la mañana. Durante esta visita, vamos a realizar lo siguiente: 
  
1. Protocolo y firma del formulario de consentimiento. Vamos a repasar el estudio en detalle y a responder 
cualquier pregunta. El formulario de consentimiento debe ser firmado antes de poder tomar parte en el estudio. 
 
2. Historia médica completa y un examen físico, con el peso, la altura, y la medición de la presión arterial. 
 
3. Un ECG se realizará para examinar la función de su corazón. 
 
4. Los análisis de sangre en ayunas para asegurarse de que usted se encuentra en buen estado de salud. El 
análisis examinará el recuento de células de la sangre, función hepática y renal, niveles de colesterol, los niveles 
de azúcar e insulina en sangre, pruebas de función tiroidea, nivel de la inflamación, así como muestras de sangre 
de reserva para ser preservadas para poder examinar durante futuras investigaciónes. También realizaremos 
pruebas para determinar si usted tiene alguna diferencia en genes que pueden ser importantes para el 
metabolismo y el peso corporal. Además para buscar algunos genes que ya nosotros pensamos que son 
importantes para el peso corporal, vamos a utilizar nueva tecnología de secuenciación de DNA que se verá en 
todos los genes humanos que conocemos. Esto se conoce como “exome” y secuenciación del genoma. Esta 
nueva tecnología nos permite mirar el ADN en gran detalle. 
 
5. Recogida de muestras de orina para asegurarse de que sus riñones funcionan normalmente, que no está 
tomando cualquier droga ilícita, y una prueba de embarazo (para las mujeres en edad fértil). 
 
6. Prueba de tolerancia a la glucosa oral. Vamos a realizar una prueba para examinar si usted tiene diabetes, la 
llamamos prueba de tolerancia a la glucosa de 2 horas. Va a tomar una taza de agua con azúcar y luego se 
tomarán muestras 1 y 2 horas después para mirar su nivel de azúcar en la sangre. 
 


 
  
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7. Absorciometría dual de rayos X (DEXA) para examinar su composición corporal. La prueba consiste en 
permanecer inmóvil sobre una mesa mientras una pequeña cámara pasa sobre su cuerpo. La dosis de los rayos X 
es mucho menor que la cantidad que se obtiene de una radiografía de pecho normal. La cantidad total de tiempo 
para realizar esta prueba será de unos 20 a 30 minutos. 
 
Visita Inicial 
  
Si reúne los requisitos para participar en el estudio, se le cita para la visita inicial. Le pediremos que permanezca en 
ayunas durante 10 horas antes de llegar a la clínica y no comer o beber nada, excepto agua por la mañana. Usted será 
visto en un dia entre semana en el Centro Clínico de los Institutos Nacionales de Salud, y la visita tomará alrededor de 8 
horas para completarse. Durante esta visita vamos a realizar lo siguiente:  
 
1. Intervalo de historia clínica y examen físico, con el peso, la altura, y la medición de la presión arterial. También 
se completará un cuestionario. 
 
2. Los análisis de sangre en ayunas para mirar su metabolismo basal y los niveles inflamatorios, así como 
muestras de sangre de reserva para ser preservados para las pruebas de investigación adicionales posibles, 
incluyendo una muestra para futuro análisis genético. Vamos a insertar una pequeña aguja en la vena (una vía 
intravenosa o IV) con el fin de obtener las muestras de sangre. 
 
3. Obtención de muestras de heces, obtendremos dos muestras de heces para conservar para futuros 
experimentos. Como parte de esta colección, le pediremos que mantenga un record de su dieta por 24 horas en 
un formulario que se le entregara a usted, y asi ver como la dieta puede afectar los resultados de las pruebas de 
heces. Los resultados de este “diario de nutricion” irá con un nutricionista. 
 
4. Obtención de muestras de orina como se describe antes. También vamos a recoger la orina durante su visita a 
ahorrar para futuros experimentos. 
 
5. Prueba de tolerancia a la glucosa intravenosa muestreado frecuentes.  Este estudio nos dice mucho 
acerca de cómo su cuerpo utiliza el azúcar, qué tan bien está funcionando su insulina y cómo es la sensibilidad de 
su cuerpo a la insulina. El estudio FSIVGTT se hace mientras usted descansa en una cama. Una segunda línea IV 
se coloca en su brazo. Le daremos un poco de agua de azúcar en una vía intravenosa durante un período de 2 
minutos. Entonces vamos a tomar muestras de sangre de la otra IV en -15, -10, -5, -1, 2, 3, 4, 5, 6, 8, 10, 14, 
19, 22, 25, 30, 40, 50, 70, 100, 140, y 180 minutos (un total de 3 horas ) para medir los niveles de azúcar e 
insulina . Exactamente a los 20 minutos en la prueba, le daremos una pequeña cantidad de insulina a través de la 
IV. Un médico o enfermera practicante estará presente durante la primera hora del estudio. Usted puede ver la 
televisión durante esta prueba. 
 
6. Tomografía Computarizada (TC) del abdomen para observar donde se tiende a almacenar su grasa. La 
prueba consiste en permanecer quieto en una mesa móvil que pasa por un gran anillo donde esta ubicada la 
cámara. La prueba implica radiación, pero solo porque tomaremos una foto de su abdomen, el método que se 
utilizará minimiza su exposición. La cantidad total de tiempo para realizar esta prueba será de unos 20 a 30 
minutos 
 
7. Subcutánea Biopsia de grasa. Para examinar el nivel de ciertas moléculas en el tejido graso, se tomará una 


 
  
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pequeña muestra de tejido graso de debajo de la piel de su abdomen a través de una técnica de "mini-
liposucción". Para adormecer el área donde se tomarà la muestra, se utilizará la lidocaína, un anestésico local. 
Una aguja se utilizará para extraer una porción de tejido graso que mide alrededor de 1 ½ cucharaditas. Un 
vendaje se aplica entonces al sitio de inserción de la aguja. Podemos darle algún medicamento para el leve dolor, 
como Tylenol o medicamento más fuerte si es necesario, después de la biopsia. La biopsia se tomará de un lugar 
del cuerpo que normalmente está cubierto y que no se ve fácilmente. 
 
8. Los medicamentos de dispensación de Estudio. Se le dará un suministro de aproximadamente 8 semanas 
de la medicación del estudio para ser tomado dos veces al día (mañana y tarde/noche) en casa. El medicamento 
se puede tomar con o sin alimentos. Le daremos una alarma de recordatorio para ayudarle a recordar cuándo 
tomar su medicamento. Si se olvida de tomar una dosis, tómela tan pronto como lo recuerde. Pero si está dentro 
de las 4 horas de la hora de su siguiente dosis, no tome una dosis doble. Sólo tome la dosis olvidada. 
 
Visita Ambulatoria Corta 
  
Para asegurarse de que está tomando bien el medicamento, usted será visto en un día de la semana en el Centro Clínico 
de los Institutos Nacionales de Salud. Esta visita se tomara alrededor de 2 horas en completarse. Le pedimos que traiga 
su botella de píldoras con usted. Durante esta visita vamos a realizar lo siguiente:  
 
1. Intervalo de historia clínica y examen físico, con el peso, la altura, y la medición de la presión arterial. 
 
2. Análisis de sangre en ayunas, para asegurarse de que está en buen estado de salud, para examinar sus niveles 
de inflamación, así como muestras de sangre de reserva para ser preservado para las pruebas adicionales 
futuras.  
 
3. Recogida de muestras de orina como se describe antes. 
 
4. Los medicamentos de dispensación de Estudio. Le daremos otra botella de la medicación del estudio (para 
un periodo de cerca de 8 semanas) para que le dure hasta la visita final (3 meses). Al igual que antes, si olvida 
tomar una dosis, tómela tan pronto como lo recuerde. Pero si está dentro de las 4 horas de la hora de su 
siguiente dosis, no tome una dosis doble. Omita la dosis olvidada. 
  
Visita Final 
  
Le pediremos traer su botella con pastillas sobrantes de su anterior visita. Le pedimos permanecer en ayunas durante 10 
horas antes de llegar a la clínica y no comer o beber nada excepto agua por la mañana. Usted será visto en un día entre 
semana en el Centro Clínico de los Institutos Nacionales de Salud, y la visita se llevará alrededor de 8 horas para 
completar. Durante esta visita vamos a realizar lo siguiente:  
 
1. Intervalo historia clínica y examen físico, con el peso, la altura, y la medición de la presión arterial  
2. Análisis de sangre en ayuno como se describe anteriormente. Vamos a insertar una pequeña aguja en la vena 
(una vía intravenosa o IV) con el fin de obtener muestras de sangre. 
3. Recogida de muestras de heces como se describe antes.  
4. Recogida de muestras de orina tal como se describe antes. 
5. Prueba muestreado frecuentes tolerancia a la glucosa intravenosa (FSIVGTT) como se describe antes. 


 
  
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6. DEXA Scan como se describe antes. 
7. CT Scan como se describe antes 
8. Grasa subcutánea biopsia como se ha descrito antes 
9. Cuestionario final para contarnos acerca de su experiencia de participar en nuestro protocolo. 
 
Visita Opcional 
  
Debido a que nos gustaría ver si la colchicina seguirá teniendo efectos positivos duraderos en la regulación del 
metabolismo de su glucosa, la inflamación, y/o su salud cardiovascular, incluso después de haber dejado de tomarlo, 
invitamos a los pacientes a volver al Centro Clínico de los NIH 3 meses después de terminar la medicación del estudio 
para repetir las mismas pruebas. 
  
Al igual que antes, le pedimos que permanecer en ayunas durante 10 horas antes de llegar a la clínica y no comer o 
beber nada, excepto agua por la mañana. Usted será visto en un día entre semana en el Centro Clínico de los Institutos 
Nacionales de Salud, y la visita llevará alrededor de 8 horas para completarse. Durante esta visita vamos a realizar lo 
siguiente: 
 
1. Intervalo historia clínica y examen físico, con el peso, la altura, y la medición de la presión arterial   
2. Análisis de sangre el ayuno como se describe anteriormente. Vamos a insertar una pequeña aguja en la vena 
(una vía intravenosa o IV) con el fin de obtener muestras de sangre. 
3. Recogida de muestras de heces como se describe antes.  
4. Recogida de muestras de orina tal como se describe antes. 
5. Prueba muestreado frecuente de tolerancia a la glucosa intravenosa (FSIVGTT) como se describe 
antes. 
6. DEXA Scan como se describe antes. 
7. CT Scan como se describe antes. 
8. Grasa subcutánea biopsia como se ha descrito antes 
  
Cuando el estudio se haya completado, volverá al cuidado de su médico de cabecera. La participación en este estudio no 
compromete al NIH a su cuidado a largo plazo. 
  
Los resultados de pruebas realizadas en el NIH 
  
Estaremos midiendo muchas cosas en su sangre durante sus visitas, y podríamos descubrir algún problema médico que 
requiere tratamiento. Ud. no recibirá de forma rutinaria tratamiento para cualquier condición de salud descubierto. Sin 
embargo, se le informará sobre estos hallazgos (por ejemplo: presión arterial alta) y cualquier información de importancia 
médica que resulten de análisis de sangre o del examen físico, serán remitidos a su médico de atención primaria en su 
solicitud. Algunos de estos problemas médicos podrían impedir su participación más en el estudio. 
 
Riesgos y molestias 
  
1. El examen físico. Un médico o una enfermera puede tener que le examinar pidiéndole que se quite su ropa, 
con las precauciones adecuadas para proteger su privacidad. Algunos pueden encontrar este examen vergonzoso. 
 
2. Exposición a la radiación: Este estudio de investigación implica la exposición a la radiación de tres imagenes 


 
  
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DEXA y tres tomografías computarizadas. Tenga en cuenta que esta exposición a la radiación no es necesario 
para su atención médica y es sólo para fines de investigación. El Comité de Seguridad Radiológica NIH ha 
revisado el uso de la radiación en este estudio de investigación y ha aprobado este uso ya que implica un riesgo 
mínimo y necesario para obtener la información de investigación deseada.  
 
Aunque cada órgano recibirá una dosis diferente, la cantidad de exposición a la radiación que recibirá anualmente 
de este estudio es igual a una exposición uniforme de todo el cuerpo a 0.093 rem. Este valor calculado se conoce 
como la "dosis efectiva" y se utiliza para relacionar la dosis recibida por cada órgano a un solo valor. La cantidad 
de radiación que recibirá en este estudio es inferior a la pauta de dosis establecido por el Comité de Seguridad 
Radiológica NIH para los sujetos de investigación. Esta pauta establece una dosis efectiva de 5 rem recibido por 
año. 
 
Por comparación, la persona promedio en los Estados Unidos recibe una exposición a la radiación de 0,3 rem por 
año a partir de fuentes naturales, como el sol, el espacio exterior, y de materiales radiactivos que se encuentran 
naturalmente en el aire y el suelo. Si desea más información sobre la radiación y los ejemplos de los niveles y 
forma de exposicion a otras fuentes, por favor pregunte al investigador para obtener una copia del folleto 
titulado, An Introduction to Radiation for NIH Research Subjects. 
 
3. La extracción de sangre. La cantidad de extracción de sangre es muy por debajo de la directriz del NIH para 
una cantidad segura de extracción de sangre (550 cc cada 8 semanas). Un pequeño moretón se puede formar en  
 
cualquier sitio donde se toma la sangre. El riesgo de infección o desmayo es muy pequeña. La inflamación o 
coagulación de una vena también pueden ocurrir raramente. 
 
Una parte de su sangre será enviado a otro laboratorio dentro del NIH para examinar sus niveles de inflamación. 
Las muestras serán codificadas, y sólo los investigadores de este estudio tendrán acceso a la identidad de las 
muestras 
 
4. Recogida de muestras de heces no tiene ningún riesgo, y sólo debe tomar un momento para recogerlas. Las 
muestras serán codificadas, y sólo los investigadores de este estudio tendrán acceso a la identidad de las 
muestras. 
 
5. La recogida de muestras de orina no tiene ningún riesgo y sólo toma un momento para completar. Si el 
resultado es positivo para una sustancia ilícita, el resultado será parte de su expediente médico NIH. 
 
6. Los cuestionarios no son peligrosos, pero pueden ser un inconveniente debido al tiempo necesario para su 
realización.  
 
7. Prueba oral de tolerancia a la glucosa. Esta prueba es un inconveniente debido al tiempo que se tarda en 
completar. Los únicos riesgos de este tipo de estudio son las descritos para cualquier extracción de sangre, así 
como el desarrollo de las náuseas por la glucosa oral. Algunos pacientes pueden desarrollar de forma transitoria 
niveles altos de azúcar en la sangre a partir de la glucosa, pero deben normalizarse a las pocas horas y no deben 
ser clínicamente significativos. 
 
8. Prueba de tolerancia a la glucosa intravenosa. Esta prueba es un inconveniente debido al tiempo que se 


 
  
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tarda en completar. Usted puede ver la televisión durante esta prueba. Los únicos riesgos de este tipo de 
estudios son las descritas para cualquier extracción de sangre, la posibilidad de una ligera sensitividad en el brazo 
al recibir la infusión de azúcar, (esa sensitividad desaparece al cabo de unos minutos con el roce suave del 
brazo), y la posibilidad de un bajo nivel de azúcar en la sangre durante el estudio. Cuando la azúcar en sangre 
esta baja (menos de 50 mg/dl), los participantes pueden tener hambre, tener dolor de cabeza, sentirse 
temblorosos o mareados o pueden llegar a ponerse sudorosos. Con azúcar en la sangre muy bajos (menos de 30 
mg /dl) participantes pueden tener problemas para hablar, dificultad para despertar, e incluso tener convulsiones.  
 
Sin embargo, en la prueba que estamos haciendo, le estaremos dando azúcar extra para elevar el azúcar en la 
sangre por encima de lo normal, y luego vamos a tratar de traerlo de vuelta a la normalidad (95-105 mg / dL) 
con insulina. Para ello, vamos a medir el azúcar en la sangre a los 2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 24, 27, 30, 40, 
50, 70, 90, 120, 140, 160, y 180 minutos (un total de 3 horas). Un médico o enfermera practicante estará 
presente durante la primera hora de su prueba para asegurarse de que todo funciona correctamente. Esperamos 
que la posibilidad de un nivel de azúcar en sangre bajo sea muy pequeña. Si un bajo nivel de azúcar en la sangre 
no sube por sí sola con rapidez, se detendrá la prueba y se le dará el azúcar por vía IV para elevar el azúcar en la 
sangre a la normalidad 
 
9. Biopsias de grasa. Los posibles efectos secundarios de la biopsia son el dolor durante y durante dos o tres días 
después del procedimiento. Aunque rara vez, la zona de la biopsia puede estar sensible o adolorida o tener 
moretones o hinchazón durante 2-3 semanas. Heridas biopsia suelen sanar con una cicatriz muy pequeña, casi 
imperceptible, pero a veces una cicatriz elevada (queloides) o bulto visible puede resultar. Su riesgo es 
ligeramente mayor si usted es afroamericano. Inyección de lidocaína para adormecer antes de biopsias de grasa 
puede causar un poco de ardor suave antes de que llegue el entumecimiento. Efectos adversos raros incluyen la 
infección en los sitios de biopsia o una reacción alérgica a la lidocaína que puede llevar a una erupción y/o 
hinchazón de la zona de inyección. Si usted sabe que es alérgico a la lidocaína, cambiaremos a otro anestésico 
local. Otro de los riesgos del procedimiento es sangrado menor en el área de la biopsia. Algunos medicamentos  
pueden aumentar la cantidad de sangrado de la biopsia. Si está tomando medicamentos como Coumadin, Plavix 
o aspirina para adelgazar la sangre, usted no tendrá una biopsia. Si está tomando aspirina o medicamentos no 
esteroides como Advil para el dolor tendrá que dejar de tomar estos medicamentos durante una semana antes de 
realizar la biopsia. 
 
10. Medicamentos. Los efectos adversos más comunes de los medicamentos utilizados en este estudio son: 
náuseas, vómitos, diarrea y dolor abdominal. Se han observado algunos efectos secundarios raros (<1%) son los 
siguientes: disminución de la producción de glóbulos rojos (que podría hacer que se sienta cansado), glóbulos 
blancos (que puede hacer más susceptibles a las infecciones), y/o plaquetas (que pueden hacerle más 
susceptibles a la aparición de moretones o sangrado), hormigueo (neuropatía), mareo, dolor muscular o 
debilidad, erupción, reacción alérgica, disminución del recuento de espermatozoides , y aumento de los niveles de 
enzimas hepáticas. Estos síntomas generalmente ocurren en personas con problemas médicos subyacentes, o 
estaban en ciertos medicamentos, que les predispone a tener la reacción. En general, estos síntomas se 
resolvieron dentro de una semana una vez que se suspende el medicamento. Aunque la colchicine se ha utilizado 
durante unos 2000 años para la gota, al igual que con cualquier medicamento, siempre existe la posibilidad de 
efectos secundarios imprevistos. Le supervisaremos por todos los efectos adversos. Si se desarrollan (severos) 
efectos adversos, vamos a disminuir la dosis, interrumpir temporalmente o suspender la medicación. 
  
Si usted experimenta cualquiera de los siguientes efectos, póngase en contacto con nuestro equipo de inmediato: 


 
  
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• 
Debilidad muscular o dolor 
• 
El entumecimiento u hormigueo en los dedos o dedos de los pies 
• 
Sangrado o moretones inusuales 
• 
La diarrea grave o vómitos 
 
No hay estudios bien controlados adecuados sobre el uso de colchicine durante el embarazo. Los datos de un 
número limitado de estudios publicados no encontraron evidencia de un mayor riesgo de aborto involuntario, 
muerte, o efectos teratogénicos en las mujeres embarazadas que usan colchicina. Sin embargo, la colchicine 
mostró defectos de nacimiento en las crías de ratas embarazadas. Si usted cree que puede quedar embarazada,  
le pediremos que no participe en este estudio. 
  
• 
Tomar ciertos medicamentos con colchicina puede hacer que subir demasiado su nivel de colchicina, 
especialmente si usted tiene problemas renales o hepáticos (consulte "Guía del Medicamento" para más 
información). 
• 
Incluso los medicamentos que usted toma por un corto período de tiempo, tales como antibióticos, 
pueden interactuar con colchicina y causar efectos secundarios graves o la muerte. Por favor díganos 
acerca de cualquier medicamento que usted necesita tomar para que podamos asegurarnos de que 
puede seguir utilizando colchicina. 
• 
Evite beber jugo de toronja, ya que puede interferir con la capacidad del cuerpo para desglosar 
colchicina 
  
Mantenga el medicamento fuera del alcance de los niños. 
  
 
11. Las pruebas de ADN. Si nos permite estudiar su ADN, lo vamos a utilizar para la secuenciación del genoma. La 
secuenciación del genoma es una prueba que nos podrían dar diferentes tipos de resultados. Estos incluyen: 
a. Podríamos identificar cambios en los genes que están relacionados con el metabolismo y el peso corporal.  
b. Podríamos identificar cambios en los genes que contribuyen a otras enfermedades o problemas. 
c. Podríamos identificar los cambios en los genes que no son conocidos por causar ninguna enfermedad. Estos son 
conocidos como variaciones normales. 
d. Podríamos encontrar cambios en los genes que son nuevos y de importancia clínica incierta. Esto significa que no 
se sabe si podrían causar o contribuir a una enfermedad o si son variaciones normales. 
  
No todos los cambios genéticos tendrán implicaciones para la salud de su familia. Los cambios en los genes que 
tienen implicaciones para la salud de su familia: 
  
1. Ya han causado problemas de salud. 
2. Pueden causar un problema de salud en el futuro. 
 
Uno de los objetivos de este estudio es identificar los cambios en los genes que pueden estar implicados en la 
obesidad. Esta investigación puede tomar años. Sin embargo, si se identifica una causa genética o la causa probable 
de la obesidad , con su permiso, nos pondremos en contacto con usted. Por favor, háganos saber su preferencia con 
sus iniciales en una de estas dos declaraciones: 
  
______ Me gustaría ser contactado con la información sobre los avances de este estudio y contactado acerca de 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  10  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
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P.A.: 09-25-0099 
 
cualquier resultado relacionado con la obesidad. Entiendo que esta investigación llevará años y que una anormalidad 
específica no se puede identificar en mí. 
  
______Por favor no se contacte conmigo acerca de la marcha de este estudio o cualquier cambio de genes 
específicos relacionados con la obesidad.  
 
Si detectamos un cambio genético que podría ser importante para usted, entonces vamos a tener que confirmar este 
resultado en un laboratorio certificado. Por esta confirmación, le pediremos una nueva muestra de ADN a usted. En la 
mayoría de los casos esto implicará la obtención de una pequeña muestra de sangre (1-2 cucharaditas). En algunos 
casos podemos obtener suficiente ADN para confirmar un cambio genético por limpiando el interior de la mejilla. 
Usted puede decidir, si desea hacerlo más adelante, si nos comunicamos con usted con la información de que hemos 
encontrado una posible diferencia genética importante. 
  
La identificación de cambios genéticos que no están relacionados con la condición que se está estudiando, se conoce 
como información médica incidental. 
  
Vamos a encontrar cambios genéticos en todo el mundo que estudiamos, pero estamos mirando sólo específicamente 
para los genes relacionados con el metabolismo y el peso corporal. No vamos a analizar su ADN para los cambios que 
no están relacionados con el metabolismo y el peso corporal. Aun así, algunos cambios en los genes no relacionados 
con el metabolismo y el peso corporal se detectarán. 
  
Nosotros sólo le informaremos de los cambios que tienen importancia médica urgente y se beneficiarían de un 
tratamiento médico temprano. Un ejemplo de esto sería un cambio en el gen que causa cáncer y en la que se 
beneficiaría de la detección temprana. No le informará de todos los cambios en los genes que tienen inciertas 
implicaciones para la salud. Por ejemplo no vamos a informar de los cambios genéticos que predisponen a los 
individuos sólo a la enfermedad. Un ejemplo de esto sería un cambio en el gen que influye en el riesgo de 
enfermedades del corazón, pero en el que el desarrollo de la enfermedad depende de muchos factores genéticos y no 
genéticos (tales como la dieta y el tabaquismo). Si nos encontramos con un cambio en un gen que es importante 
para la salud de su familia, sólo le daremos los resultados si el cambio ha sido confirmado por un laboratorio 
certificado. Para asegurarse de que no se ha producido un error, tendríamos que obtener una nueva muestra de ADN 
a partir de que se confirmen los resultados experimentales. 
  
Además de saber lo que encontramos, nos gustaría que conociera las limitaciones de la secuenciación del genoma y 
lo que no vamos a ser capaces de decirle acerca de los cambios que encontramos. 
  
1. No todos los cambios en los genes que causan la enfermedad serán detectados. 
2. Algunos de los cambios que no se conocen actualmente para causar problemas de salud podrían causar  
problemas de salud en el futuro. No podemos prometer tener la capacidad de decirle a usted acerca de esos 
cambios en el futuro. 
3. No le dirá acerca de cambios en los genes que no se sabe que tienen consecuencias para la salud, ni vamos a 
informarle sobre cambios en los genes que sólo tienen consecuencias reproductivas. 
4. Esta secuenciación de genes no puede ser sustituido por las pruebas de diagnóstico recomendado por otro 
médico. 
  
 


 
  
CONTINUATION SHEET for either: 
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NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  11  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Por favor, coloque sus iniciales en todas las siguientes declaraciones para indicar que usted entiende la medida en 
que le informaremos sobre los cambios genéticos accidentales que encontremos: 
 
______ Entiendo, que voy a estar informado sólo de cambios genéticos que los investigadores implicados 
en este estudio piensen que son urgentemente importantes para la salud de mi familia y que el 
conocimiento de estos cambios tiene el potencial de un beneficio significativo para mí o mi 
familia. 
 
______ Entiendo que los investigadores no van a buscar específicamente cambios en los genes no 
relacionados con el metabolismo y el peso corporal, y que la identificación de otros genes que 
causan enfermedades sólo ocurrirá por casualidad dependiendo del análisis que se realiza. 
  
______ Entiendo perfectamente que a pesar de que podrían tener consecuencias de salud o 
reproductivas, no se me hablará de todos los cambios genéticos identificados que no están 
relacionados con el metabolismo y el peso corporal. 
 
Si se detecta un cambio en el gen no relacionado con el metabolismo y el peso corporal y los investigadores 
sentimos que cumple con los requisitos de tener importancia médica urgente para que usted se beneficie de un 
tratamiento médico, a continuación, se le dará la opción para aprender o no aprender acerca del cambio genético 
encontrado. Usted puede elegir no ser contactado en absoluto si esa es su preferencia. Una excepción a su 
capacidad de elegir si desea o no saber acerca de un cambio en un gen, sería un cambio en un gen que los 
investigadores consideran que es de vital importancia para su salud. Un ejemplo de esto sería un cambio en el 
gen que tiene una alta probabilidad de causar cáncer o una enfermedad para la cual el tratamiento temprano 
sería beneficioso. Antes de confirmar el resultado en un laboratorio clínico nos pondremos en contacto con usted 
para obtener una nueva muestra de ADN. 
 
Si usted tiene un cambio en un gen con urgentes implicaciones para la salud, el NIH confirmará el cambio 
genético presente en uno de los miembros de su familia. Discutiremos los resultados con usted para que pueda 
saber si alguien más en su familia podría ser un portador de este mismo cambio. Podemos ayudarle a organizar 
las pruebas que haya que hacer, pero el NIH no podemos prometer realizar o pagar por las pruebas clínicas 
necesarias para confirmar o determinar quién más en su familia puede tener este cambio en su ADN. 
  
Una vez que se confirma un cambio en un gen, vamos a discutir los resultados con usted y hacer 
recomendaciones sobre apropiado seguimiento médico. El NIH no puede prometer realizar o pagar por los 
exámenes médicos recomendados o evaluaciones. 
  
Es posible que un cambio genético no se confirmará en las pruebas posteriores. Esto podría ser debido a un error 
en la secuenciación de ADN o un error en el procesamiento del ADN o líneas celulares. Aunque es agradable para 
Ud. que no se confirme el problema, esto puede causar un poco de ansiedad y preocupación que de otra manera 
no habría experimentado. 
  
Por favor, háganos saber sus preferencias colocando sus iniciales en una de las siguientes afirmaciones: 
  
______ Yo QUIERO ser re-contactado si se descubren variantes genéticas con consecuencias urgentes 


 
  
CONTINUATION SHEET for either: 
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NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  12  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
para la salud, durante esta prueba de investigación. 
  
______ NO deseo volver a ser contactado si se descubren variantes genéticas con consecuencias 
urgentes para la salud durante esta prueba de investigación. Entiendo que una excepción a esta 
elección, como se describió anteriormente, se hará para un cambio en el gen de importancia 
médica fundamental. 
  
Riesgos emocionales y psicológicos de la prueba de ADN. La identificación de los cambios en los genes 
puede causar problemas emocionales y psicológicos. En algunas situaciones se podría recomendar asesoría 
psicológica. 
  
1. Aprender sobre el riesgo de enfermedad que en su familia puede ser angustiante. 
2. Aprender que algo que sucede en un gen suyo, puede no suceder en su hijo, puede ser angustiante. 
3. Otros miembros de su familia podrían ponerse molestos al saber que ellos pueden estar en riesgo de un 
trastorno debido a su participación en este estudio. 
  
Ud. Puede permanecer falsamente tranquilo acerca de su estado de salud si nosotros no le reportamos ningún 
cambio en su caso. 
  
Otros riesgos de las pruebas genéticas. Si confirmamos un cambio genetico en su ADN en un laboratorio de 
diagnóstico, esta información será parte de su expediente médico en el NIH. Algunas personas se preocupan de 
que la información acerca de ellos de sus registros médicos podrían ser dadas a conocer. Posibles problemas 
incluyen el seguro o la discriminación laboral. Medidas para proteger la confidencialidad de su información  se 
describen a continuación. Estos problemas también pueden ocurrir si usted divulga su propia información o 
acepta que sus registros de investigación sean liberados. 
  
Hay leyes estatales y federales que protegen contra la discriminación genética. Una ley federal llamada la Ley de 
No Discriminación por información Genética (GINA), generalmente hace que sea ilegal que las compañías de 
seguros de salud, planes de salud de grupo, y la mayoría de los empleadores discriminen contra usted basado en 
su información genética. Según esta ley, las compañías de seguros de salud o planes de salud de grupo (hasta el 
21 de mayo de 2010) no puede solicitar su información genética, o utilizarlo para tomar decisiones sobre su 
elegibilidad o primas; y los empleadores no pueden utilizarlo en la decisión de contratar, promover, ni puede 
despedirlo, o en el establecimiento de los términos de su empleo (a fecha de 21 de noviembre 2009). 
  
Tenga en cuenta que esta ley federal no le protege contra la discriminación genética por las compañías que 
venden seguros de vida, seguro de invalidez, o un seguro de cuidado a largo plazo. 
 
Este enlace contiene detalles sobre esta política: 
http://www.genome.gov/Pages/PolicyEthics/GeneticDiscrimination/GINAInfoDoc.pdf 
  
Usted puede preguntar a su equipo de investigación para obtener información adicional o una copia de la Ley de 
Discriminación por Información Genética de 2008 documento informativo. 
  
Los estudios genéticos pueden descubrir relaciones familiares inesperados. Por ejemplo, es posible que podamos 
enteramos de que un miembro de la familia no es el hijo biológico de los padres con los que él o ella vive (por 


 
  
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STUDY NUMBER: 
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CONTINUATION:  page  13  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
ejemplo, debido a la adopción). No proporcionaremos normalmente este tipo de información a cualquier miembro 
de la familia o al médico de referencia. Sin embargo, podemos hacer excepciones en circunstancias 
extraordinarias si esta información se requiere para la atención médica de las personas involucradas. Si estamos  
convencidos de que esto es necesario, vamos a proporcionar la información al médico que proporciona la 
atención médica al paciente 
   
El uso de muestras almacenadas y datos 
  
Investigaciones futuras ADN. Actualmente tenemos la intención de secuenciar los genes conocidos. Esto 
representa sólo alrededor del 1% de su secuencia de ADN. En el futuro podemos secuenciar otras partes de su 
ADN, y, finalmente, podemos secuenciar completamente su ADN. Estos estudios adicionales pueden ocurrir años 
a partir de ahora. Algunas partes de su ADN pueden ser enviadas a otros laboratorios para pruebas específicas. Si 
esto se hace el ADN será codificado y no tendrá su nombre en la muestra o en el papeleo que va al laboratorio. 
En caso de retirarse de este estudio, vamos a mantener su ADN para el análisis a menos que usted nos pida 
destruir las muestras de AND. 
  
Por favor, coloque su inicial en una de las siguientes tres declaraciones relativas a la investigación futura: 
 
______ ADN puede ser utilizado para otros tipos de futuras investigaciones relacionadas con la salud. Esta 
investigación no se limita a los estudios relacionados con la obesidad, el metabolismo y el peso corporal. 
Esta prueba puede realizarse por laboratorios de investigación que no se encuentran en el NIH. Autorizo 
el uso de estas muestras sin mi consentimiento adicional. Entiendo que no se pondrán en contacto si se 
utilizan estas muestras en el futuro. 
  
______ Entiendo que las muestras genéticas recogidas durante estas visitas NIH serán guardados y utilizados 
para futuras pruebas experimentales relacionadas con la obesidad, el metabolismo y el peso corporal. 
Esta prueba puede realizarse por laboratorios de investigación que no se encuentran en el NIH. NO 
autorizo el uso de estas muestras para ningún otro fin sin mi consentimiento adicional. Debo ser 
contactado y dar consentimiento si estas muestras se van a utilizar en el futuro. 
  
______ No utilice mi ADN para futuros estudios más allá de los descritos anteriormente en este formulario de 
consentimiento. 
  
Futuras investigaciones con muestras de sangre. Nuestros planes específicos de investigación se han 
resumido en este formulario de consentimiento. En el curso de la investigación, vamos a obtener muestras de 
sangre. Si bien podemos hacer algunas de nuestras pruebas de inmediato, es posible que desee almacenar sus 
muestras de sangre en el congelador para futuros estudios. Además, cierta información se almacenará en su 
expediente médico. En el futuro, es posible que sus muestras de sangre o registros médicos serán utilizados para 
otros fines de investigación que no se describen específicamente en este formulario de consentimiento. Si se hace 
esto, las muestras serán codificadas, y no serán identificados por su nombre. Estas muestras pueden ser 
almacenadas en un lugar separado (llamado un repositorio) que se especializa en el almacenamiento de muestras 
clínicas. Usted tiene la opción, en el futuro, de solicitar que estas muestras no se utilicen para hacer más 
ensayos. Además, es posible que alguna información obtenida de estos estudios serán publicados en la literatura 
médica. Sin embargo, su identidad no será incluida en cualquier publicación. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  14  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
Por favor, coloque su inicial en una de las dos afirmaciones siguientes: 
  
______ Entiendo que las muestras recogidas durante estas visitas NIH serán guardadas y utilizadas para futuros 
ensayos experimentales relacionados con el peso corporal, y/o el metabolismo. Esta prueba puede 
realizarse por laboratorios de investigación que no se encuentran en el NIH. Autorizo a otros usos de 
estas muestras sin mi consentimiento adicional. Entiendo que no se pondrán en contacto si se utilizan 
estas muestras en el futuro. 
  
______ Entiendo que las muestras recogidas durante estas visitas NIH serán guardadas y utilizadas para futuros 
ensayos experimentales relacionados con el peso corporal, y/o el metabolismo. Esta prueba puede 
realizarse por laboratorios de investigación que no se encuentran en el NIH. NO autorizo cualquier otro 
uso de estas muestras sin mi consentimiento adicional. Debo ser contactado y dar consentimiento si 
estas muestras se van a utilizar en el futuro. 
  
Durante todo el proceso de estudio y después, la confidencialidad de los participantes será protegida mediante el 
uso de códigos y números de historia clínica en la grabación de su información y resultados de pruebas. Sólo el 
personal médico involucrado en este estudio tendrán acceso a los nombres de los participantes, resultados de 
exámenes, y los números de código de los pacientes. 
  
Usted tiene que ser consciente de que la secuencia de ADN es como una huella digital. Teóricamente si suficiente  
información de la secuencia de ADN está disponible, alguien podría identificarlo a Ud. en base a su secuencia de 
ADN. Para facilitar la investigación genética, la información de su secuencia de ADN se puede depositar en otras 
bases de datos. En este caso, a menos que tengamos su permiso, vamos a depositar los datos de una manera 
que no permita que alguien le identifique. Por favor, comprenda que esta información no se puede eliminar una 
vez que se deposita. 
   
Por favor, coloque su inicial en una de las siguientes casillas: 
  
______ No quiero que los datos de secuencia de ADN sean depositados en cualquier base de datos que no sea la 
que está asociada con este estudio. 
______ Mis datos de secuencias de ADN pueden ser depositados en las bases de datos que limitan el acceso a la 
IRB (comité de ética) Investigadores aprobados. 
______ Mi secuencia de ADN puede ser depositada en una base de datos que está disponible sólo para los 
científicos, pero que no requiere la aprobación del IRB de estudios de investigación. Entiendo que alguien 
teóricamente me podía identificar de esta información. 
  
Los beneficios potenciales de la participación 
  
Tenemos la esperanza de que su participación en este estudio proporcionará pruebas acerca de si la colchicina ayudará 
parámetros metabólicos en individuos obesos. Sin embargo, no puede beneficiarse directamente de participar en este 
estudio. Al encontrar anomalías en cualquiera de sus resultados de la prueba, se le notificará y recibirá una copia para 
ayudarle en la búsqueda de una mayor evaluación médica. Esta información puede o no mejorar su salud.   
 Derecho de revocación y Condiciones de retiro anticipado 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  15  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
  
Usted puede retirarse del estudio en cualquier momento y por cualquier motivo y sin pérdida de beneficios o privilegios a 
los que tiene derecho. 
  
 
La discusión de los nuevos hallazgos con usted 
  
Después de que todos los participantes hayan completado el estudio, se le informará sobre cual medicina tomó y una vez 
que el estudio esté totalmente analizado, le permiten saber si la colchicina puede ayudar con la inflamación y la 
resistencia a la insulina. No hay plan general para compartir los resultados de sus pruebas individuales con usted. Sin 
embargo, si algún hallazgo sugiere que tiene un problema médico, vamos a proporcionar esta información a usted y a su 
proveedor de atención primaria. Usted puede solicitar una copia de sus pruebas de laboratorio de rutina si lo desea. 
  
Terminación de Estudios 
  
Se le puede pedir terminar su participación en este estudio en cualquier momento, si creemos que la continuación en él 
no es lo mejor para su interés médico o si no puede cumplir con los requisitos del estudio. 
  
 
Alternativas a la Participación 
  
La alternativa a este estudio es no participar. Usted puede ser elegible para otros estudios en los NIH. Usted puede 
aprender más sobre ellos a través de www.clinicaltrials.gov. 
  
Compensación 
Usted será compensado por el tiempo y los inconvenientes asociados a la participación según las directrices de 
compensación para voluntarios de investigación del NIH. La compensación para completar todas las pruebas que se han 
descrito anteriormente es: $100 por la visita de selección de pacientes ambulatorios, $50 por la visita de seguridad, y de 
$300 por cada una de las visitas inicial, final y la opcional. La cantidad total que usted podría recibir por la participación si 
completa todas las partes de este estudio es de $1050. 
  
Conflicto de intereses 
  
El NIH y los miembros de este equipo de investigación no tienen ningún interés financiero en relación con este estudio de 
investigación. 
  
Publicación de Resultados de Investigación en: www.ClinicalTrials.gov 
  
Una descripción de este ensayo clínico estará disponible en http://www.Clinicaltrials.gov, como lo requiere la ley de 
Estados Unidos. En esta pagina de web no incluirá información que pueda identificarlo. En la mayor parte del sitio Web 
incluirá un resumen de los resultados. Usted puede buscar en este sitio web en cualquier momento. 
  
______ He recibido una copia del formulario de consentimiento firmado.


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  16  of 17 pages 
 
 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
INFORMACIÓN PERTINENTE ADICIONAL 
 
1. Confidencialidad. Cuando los resultados de un estudio de investigación del NIH se dan a conocer en revistas 
médicas o reuniones científicas, no se menciona la identidad de los participantes. En la mayoría de los casos, el NIH no 
divulgará ninguna información sobre su participación en la investigación a menos que usted otorgue su permiso por 
escrito. No obstante, si usted firma una autorización de divulgación de información, por ejemplo, a una empresa 
aseguradora, el NIH le proporcionará a ésta información de su expediente médico. Esta información podría influir (en 
forma favorable o desfavorable para usted) la disposición de la aseguradora a venderle el seguro.  
 
La Ley Federal de Protección de la Vida Privada (Federal Privacy Act) protege el carácter confidencial de sus expedientes 
médicos en el NIH. Sin embargo, es importante que sepa que esta ley permite la divulgación de cierta información de su 
expediente médico sin su autorización, por ejemplo, si lo solicitan la Administración de Alimentos y Medicamentos (FDA), 
los miembros del Congreso, los agentes encargados del cumplimiento de la ley o las organizaciones autorizadas para 
efectos de acreditación hospitalaria.  
 
2. Normas sobre lesiones relacionadas con la investigación. El Centro Clínico le dará atención médica a corto 
plazo para cualquier lesión que se deba a su participación en una investigación que se realice allí. En general, ni los 
Institutos Nacionales de Salud, ni el Centro Clínico, ni el gobierno federal le darán atención médica a largo plazo ni 
indemnización económica por lesiones relacionadas con la investigación. Sin embargo, usted tiene derecho a buscar una 
compensación legal si cree que la lesión justifica dicha medida.  
 
3. Pagos. El monto del pago que reciben los voluntarios de investigación se rige por las normas de los Institutos 
Nacionales de Salud. En general, a los pacientes no se les paga por participar en los estudios de investigación en los 
Institutos Nacionales de Salud. Se le ofrecerá el reembolso de gastos de viaje y viáticos según las pautas del NIH.  
 
4. Problemas o preguntas. Si hay algún problema o usted tiene una pregunta con respecto a este estudio, a sus 
derechos como participante en un estudio de investigación clínica o a cualquier lesión relacionada con la investigación, 
debe comunicarse con el Investigador Principal, Jack A. Yanovski, MD, PhD; Building (Edificio) 10, Room (Sala) 1-3330, 
Teléfono: (301) 496-4686 o el Investigador Asociado Principal, Andrew Demidowich, MD; Building 10, Room 1-3330, 
Teléfono: (301) 496-4686.  
 
También puede llamar al representante de los pacientes del Centro Clínico, al teléfono (301) 496-2626.  
 
5. Documento de consentimiento. Le sugerimos que conserve una copia de este documento para consultarla 
posteriormente. 


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  17  of 17 pages 
 
 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
COMPLETE LAS CASILLAS CORRESPONDIENTES A CONTINUACIÓN: 
 
A. Consentimiento de un paciente adulto. 
B. Permiso otorgado por el (los) padre(s) de un paciente 
menor de edad. 
He leído la explicación relacionada con este estudio y he tenido la 
oportunidad de comentarla y hacer preguntas. Por este medio otorgo mi 
consentimiento para participar en este estudio. 
He leído la explicación relacionada con este estudio y he tenido la 
oportunidad de comentarla y hacer preguntas. Por este medio otorgo 
permiso para que mi hijo participe en este estudio. 
(Anéxese el formulario NIH 2514-2, Asentimiento de un menor de edad, 
si corresponde.) 
 
  
 
 
  
 
Firma del paciente adulto o su representante  legal       Fecha 
 
 
 
Nombre en letra de imprenta 
Firma del (los) padre(s) o del tutor legal 
Fecha 
 
 
 
Nombre en letra de imprenta 
C. Asentimiento verbal de un niño (si corresponde)  
Se le explicó a mi hijo la información contenida en el presente documento y mi hijo está de acuerdo en participar en el estudio. 
 
 
 
  
 
 
 
 
Firma del (los) padre(s) o del tutor legal 
Fecha  
Nombre en letra de imprenta 
EL USO DE ESTE DOCUMENTO DE CONSENTIMIENTO ESTÁ APROBADO 
DESDE EL 24 DE ENERO DE 2018 HASTA EL 24 DE FEBRERO DE 2019.  
 
 
 
 
  
 
 
  
 
Firma del Investigador 
Fecha 
 
 
 
Nombre en letra de imprenta 
Firma del testigo 
Fecha 
 
 
 
Nombre en letra de imprenta 
 


 
 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
               •  Adult Patient or     •  Parent, for Minor Patient 
 
 
INSTITUTE: 
National Institute of Child Health and Human Development 
 
 
STUDY NUMBER: 
14-CH-0119 
PRINCIPAL INVESTIGATOR:  Jack Yanovski, M.D. 
 
 
STUDY TITLE: 
Pilot Study of the Effects of Colchicine in Non-Diabetic Adults with Metabolic Syndrome 
 
 
Continuing Review Approved by the IRB on 01/24/18 
Amendment Approved by the IRB on 07/13/18 (S)  
 
 
Date Posted to Web: 08/03/18 
Evaluation-only 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY 
 
•   Adult Patient or    •   Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent (3) 
 
 
INTRODUCTION 
 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
 
First, we want you to know that: 
 
 
Taking part in NIH research is entirely voluntary. 
 
 
You may choose not to take part, or you may withdraw from the study at any time.  In either case, you will not 
lose any benefits to which you are otherwise entitled.  However, to receive care at the NIH, you must be taking 
part in a study or be under evaluation for study participation. 
 
 
You may receive no benefit from taking part.  The research may give us knowledge that may help people in the 
future. 
 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research treatments 
they would want to receive (such as blood transfusions).  If you have such beliefs, please discuss them with your NIH 
doctors or research team before you agree to the study. 
 
Now we will describe this research study.  Before you decide to take part, please take as much time as you need to ask 
any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other health 
professional. 
 
 
Purpose of this Study 
 
Fat cells play numerous important roles in our body including storing energy, secreting hormones, and helping regulate 
our metabolism.  Insulin is a hormone that circulates throughout our body and communicates with our fat cells and 
regulates their function. When insulin’s ability to communicate with the rest of the body begins to fail, people become 
“insulin resistant” and can go on to develop diabetes.  However, the specific details of how insulin works at the level of 
the fat cell are still poorly understood.  A purpose of this study is to better understand the timing and mechanisms behind 
insulin’s actions on the fat cell, and possibly identify new factors of why some people are more prone to developing 
diabetes. We ask you to help us understand how insulin works in the body by undergoing a series of tests. You will not be 
asked to take the study medicine (colchicine).  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 2 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
You will need to come to the NIH Clinical Center for two outpatient visits. It is important that you arrive fasting (no food 
or beverages besides water) to each of these visits.  You will be compensated for their time and inconvenience. 
 
Study Population 
 
We wish to recruit healthy adults and adults with type 2 diabetes treated only with diet. 
 
Who Can Be in This Study 
 
You may be eligible for this research study if you are greater than 18 years old, weigh less than 450 lbs, and are in 
good general health.  
 
Who May Not Be In This Study 
 
You may not be eligible for this study if you have a major medical illness that would interfere with study tests or 
measurements, such as heart, kidney, liver, lung, blood, gut, or endocrine diseases, or uncontrolled high blood 
pressure. People with type 2 diabetes who are taking medication or have hemoglobin A1c >9%, are not allowed to 
participate. If you are currently using a medication that affects sugar and fat metabolism or absorption in your body, 
you may not be eligible to participate. Also individuals who are pregnant or nursing, or planning to become pregnant, 
have had a recent weight change greater than 3% of total body weight, have been using weight reducing medications, 
have recently used colchicine, have a known allergy to colchicine, or use tobacco or nicotine (e.g. e-cigarettes) products 
will not be recruited for this study. Individuals with a history of keloid formation (who easily develop scars on their skin 
after an injury) also will not be allowed to take part in this study. 
 
Procedures of the study 
 
The study consists of two outpatient visits: an outpatient screening visit at the Clinical Center to determine eligibility 
and a baseline visit to study your metabolism.   
 
Outpatient Screening Visit 
 
This visit will take about 3 hours to complete.  You will be seen on a weekday in the Clinical Center at the National 
Institutes of Health.  We ask that you remain fasting for 10 hours before coming to the clinic and have nothing to eat or 
drink except water that morning.  During this visit, we will perform the following: 
 
1. Protocol review and signing of consent form. We will go over the study in detail, and answer any questions. 
The consent form will need to be signed before you can take part in the study. 
 
2. Complete medical history and physical exam, with weight, height, and blood pressure measurement. 
 
3. An EKG will be performed to examine your heart function. 
 
4. Fasting blood tests to ensure that you are in good health. The analysis will examine blood cell count, liver and 
kidney function, cholesterol levels, blood sugar and insulin levels, thyroid tests, inflammation level, as well as 
reserve blood samples to be preserved for additional possible research tests.  We will also plan to do tests to find 
out if you have any differences in genes that may be important for metabolism and body weight. In addition to 
looking at some genes we already think are important for body weight, we may use new DNA sequencing 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 3 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
technology that will look at all the human genes we know about. This is known as exome and genome 
sequencing. This new technology allows us to look at DNA in great detail. 
 
5. Urine sample collection to ensure that your kidneys work normally, that you are not taking any illicit drugs, 
and a pregnancy test (for women of childbearing age). 
 
6. Oral glucose tolerance test.  We will perform a test to examine whether you have diabetes, called a 2-hour 
glucose tolerance test.  You will drink a cup of sugar water and then will have your blood drawn 1 and 2 hours 
later to look at your blood sugar level. 
 
7. Dual energy x-ray absorptiometry (DEXA) to look at your body composition. The test involves lying still on a 
table while a small camera passes over your body. The dose of the x-ray is much less than the amount you would 
get from a normal chest x-ray. The total amount of time to do this test will be about 20-30 minutes. 
 
Baseline Visit 
 
If you qualify for participation in the study, you will be scheduled for the baseline visit.  We ask that you remain fasting for 
10 hours before coming to the clinic and have nothing to eat or drink except water that morning.  You will be seen on a 
weekday in the Clinical Center at the National Institutes of Health, and the visit will take about 8 hours to complete.  
During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement.  A 
questionnaire will also be performed. 
 
2. Fasting blood tests to look at your baseline metabolic and inflammatory levels, as well as reserve blood 
samples to be preserved for additional possible research tests including a sample for future genetic analysis.  We 
will insert a small needle into your vein (an intravenous line or I.V.) in order to obtain blood samples. 
 
3. Stool sample collection. We will obtain two stool samples to save for future experiments.  As part of this 
collection, we will ask you to keep track of your diet for 24 hours on a form that will be provided to you, as diet 
can affect the results of the stool testing.  You will also go over this “food record” in person with a nutritionist. 
 
4. Urine sample collection as described before. We will also collect urine over your eight hours of testing to save 
for future experiments. 
 
5. Frequently sampled intravenous glucose tolerance test (FSIVGTT).  This study tells us a lot about how 
sugar is used by your body, how well your insulin works, and how sensitive your body is to insulin.  The FSIVGTT 
study is done while you rest in bed.  A second IV line will be placed in your arm. We will give you some sugar 
water into one IV over a 2 minute period.  We will then draw blood samples from the other IV at -15, -10, -5, -1, 
2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 25, 30, 40, 50, 70, 100, 140, and 180 minutes (a total of 3 hours) to measure 
sugar and insulin levels.  Exactly 20 minutes into the test, we will give you a small amount of insulin through the 
IV.  A physician or nurse practitioner will be present during the first hour of the study. You can watch TV during 
this test. 
  
6. Computed Tomography (CT) Scan of the abdomen to look at where you tend to store your fat.  The test 
involves lying still on a movable table which passes through a large ring where the camera sits.  The test does 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 4 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
involve radiation, but because we only need to take a snapshot of your abdomen, the method that will be used 
minimizes your exposure.  The total amount of time to do this test will be about 20-30 minutes. 
  
7. Subcutaneous Fat Biopsy. To examine the level of certain molecules in your fat tissue, a small sample of fat 
tissue will be taken from under the skin of your abdomen. Lidocaine, a local anesthetic, is used to numb the area.  
A needle will be used to remove a piece of fat tissue measuring about 1 ½ teaspoons.  A bandage is then applied 
to the site of needle insertion.  We can give you some mild pain medication such as Tylenol, or stronger 
medication if needed, after the biopsy. The biopsy will be taken from a place on your body that is normally 
covered and not easily seen.  
 
When the study is complete, you will return to the care of your regular physician. Participation in this study does not 
commit NIH to your long term care. 
 
Results of Tests at the NIH 
 
We will be measuring many things in your blood during your visits, and it is possible we might uncover a medical problem 
that requires treatment.  You will not be routinely provided treatment for any health condition discovered. However, you 
will be informed about such findings (e.g., high blood pressure) and any medically important information including blood 
tests or physical exam results will be forwarded to your primary care physician at your request.  Some of these medical 
problems might prevent you from participating further in the study. 
 
Risks and discomforts 
 
1. Physical examination. A physician or a nurse practitioner may need to examine you with your clothes off, with 
appropriate precautions to protect your privacy.  Some may find this examination embarrassing. 
 
2. Radiation Exposure: This research study involves exposure to radiation from one DEXA scan and one CT scan. 
Please note that this radiation exposure is not necessary for your medical care and is for research purposes only.   
The NIH Radiation Safety Committee has reviewed the use of radiation in this research study and has approved 
this use as involving minimal risk and necessary to obtain the research information desired. 
 
Although each organ will receive a different dose, the amount of radiation exposure you will receive yearly from 
this study is equal to a uniform whole-body exposure of 0.031 rem. This calculated value is known as the 
“effective dose” and is used to relate the dose received by each organ to a single value. The amount of radiation 
you will receive in this study is below the dose guideline established by the NIH Radiation Safety Committee for 
research subjects.  This guideline is an effective dose of 5 rem received per year. 
 
For comparison, the average person in the United States receives a radiation exposure of 0.3 rem per year from 
natural background sources, such as from the sun, outer space, and from radioactive materials that are found 
naturally in the earth’s air and soil.  If you would like more information about radiation and examples of exposure 
levels form the other sources, please ask the investigator for a copy of the pamphlet called, An Introduction to 
Radiation for NIH Research Subjects. 
 
3. Blood withdrawal.  The blood withdrawal amount is well below the NIH guideline for a safe amount of blood 
withdrawal (550 cc every 8 weeks).  A small bruise may form at any site where the blood is taken.  The risk of 
infection or fainting is very small.  Inflammation or clotting of a vein also may rarely occur. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 5 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Some of your blood will be sent to other laboratories within the NIH to examine your inflammation levels.  The 
samples will be coded, and only the investigators from this study will have access to the identity of the samples. 
 
4. Stool sample collection has no risk, and should only take a moment to complete.  The samples will be coded, 
and only the investigators from this study will have access to the identity of the samples. 
 
5. Urine sample collection has no risk and should only take a moment to complete.  If you do test positive for an 
illicit substance, the result will be part of your NIH Medical Record. 
 
6.  Questionnaires are not risky, but may be inconvenient because of the time necessary to complete them. 
 
7.  Oral glucose tolerance test.  This test is inconvenient because of the time it takes to complete.  The only risks 
from this kind of study are those described for any blood draw, as well as developing nausea from the oral 
glucose. Patients may transiently develop high blood sugar levels from the glucose, but it should normalize within 
a few hours and should not be clinically significant. 
 
8. Intravenous glucose tolerance test. This test is inconvenient because of the time it takes to complete.  You 
can watch TV during this test. The only risks from these kinds of studies are those described for any blood draw, 
the possibility of slight arm tenderness in the arm receiving the sugar infusion, (this tenderness goes away within 
a few minutes with gentle rubbing of the arm), and the possibility of a low blood sugar during the study.  With 
slightly low blood sugars (less than 50 mg/dL), participants may get hungry, have a headache, feel shaky or 
dizzy, may become drowsy, or may become sweaty.  With very low blood sugars (under 30 mg/dL) participants 
may have trouble speaking, be difficult to arouse, and even have seizures.  However, in the test we are doing, we 
will be giving you extra sugar to raise your blood sugar above normal, and then we will try to bring it back to 
normal (95-105 mg/dL) with insulin.  To do this, we will measure blood sugar at 2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 
24, 27, 30, 40, 50, 70, 90, 120, 140, 160, and 180 minutes (a total of 3 hours).  A physician or nurse practitioner 
will be present during the first hour of your test to make sure everything is working properly.  We expect that the 
chance of even a slightly low blood sugar is very low.  If a low blood sugar does not come up on its own quickly, 
the test will be stopped and you will be given sugar by vein to raise the blood sugar to normal. 
 
9. Fat tissue biopsies. Possible side effects of the biopsy procedure are pain during and for two to three days after 
the procedure, although rarely the biopsy site may be tender or sore or have bruising or swelling for 2-3 weeks. 
Biopsy wounds usually heal with a very small, nearly unnoticeable scar, but sometimes a raised scar (keloid) or 
visible lump may result. Your risk is slightly higher if you are African American. Lidocaine injection for numbing 
before fat biopsies may cause some mild burning before the numbing takes effect. Rare adverse effects include 
infection at the biopsy sites or an allergic reaction to Lidocaine that may lead to a rash and/or swelling of the 
injected area. If you know you are allergic to Lidocaine, we will change to another local anesthetic. Another risk of 
the procedure is minor bleeding in the area of the biopsy. Some medications may increase the amount of bleeding 
from the biopsy. If you are taking medications such as Coumadin, Plavix or aspirin to thin your blood, you WILL 
NOT have a biopsy. If you are taking aspirin or non-steroidal medications such as Advil for pain you will need to 
stop taking these medicines for one week before the biopsy is performed. 
 
 
10. DNA testing. If you allow us to study your DNA, we will use it for genome sequencing. Genome sequencing is a 
test that could give us different kinds of results. These include: 
a. We could identify changes in genes that are related to metabolism and body weight. 
b. We could identify changes in genes that contribute to other diseases or problems.  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 6 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
c. We could identify changes in genes that are not known to cause any disease. These are known as normal 
variations.  
d. We could find changes in genes that are new and of uncertain clinical importance. This means that we do not 
know if they could cause or contribute to a disease or if they are normal variations. 
 
One of the goals of this study is to identify changes in genes that may be involved in obesity. This research may 
take years. If however we identify a genetic cause or likely cause of obesity, with your permission, we will contact 
you. Please let us know your preference by initialing one of these three statements: 
 
______  I would like to be contacted with information about the progress of this study and contacted 
about any results related to obesity. I understand that this research will take years and that a 
specific abnormality might not be identified in me. 
 
______ Please do not contact me regarding the progress of this study or any specific gene changes 
related to obesity. 
 
______ I do NOT authorize any genetic samples to be collected during these NIH visits. 
 
Identifying gene changes that are not related to the condition being studied is known as incidental medical 
information.  We will find gene changes in everyone that we study, but currently we are only specifically looking 
for genes related to metabolism and body weight. Even so, some gene changes not related to metabolism and 
body weight might be detected.  
 
We will only inform you only of changes that have urgent medical significance and would benefit from early 
medical treatment. An example of this would be a gene change that causes cancer and where you would benefit 
from early screening. We will not inform you of all gene changes that have uncertain health implications or that 
only predispose individuals to disease. An example of this would be a gene change that influences the risk of 
heart disease, but where the development of the disease is dependent on many genetic and non-genetic (such as 
diet and smoking) factors.  Also we will not inform you of gene changes that may have reproductive 
consequences, such as impotence or infertility. 
 
If we find a gene change of urgent medical significance, we will only be able to give you those results once the 
change has been confirmed in a certified laboratory.  For this confirmation, we will ask for a new sample of DNA 
from you. In most cases this will involve obtaining a small sample of blood (1-2 teaspoons). Sometimes we can 
obtain enough DNA to confirm your genetic change by swiping the insides of your cheek. 
 
Once a gene change is confirmed, we will discuss the results with you and make recommendations regarding 
appropriate medical follow up. The NIH cannot promise to perform or pay for recommended medical tests or 
evaluations.  Also, it is possible that a gene change will not be confirmed on subsequent testing. This could be 
due to an error in the DNA sequencing or an error in processing the DNA or cell lines. Although you likely will be 
glad that we did not confirm a problem, this may cause some anxiety and concern that you otherwise would not 
have experienced. 
 
Please let us know your preferences by initialing one of the following statements (You are allowed to change your 
mind in the future): 
 
______ I DO want to be re-contacted if genetic variants with urgent health implications are discovered 
during this research testing. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 7 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
______ I DO NOT want to be re-contacted if genetic variants with urgent health implications are 
discovered during this research testing.  
 
If we find a gene change with urgent health implications, the NIH can confirm the genetic change present in one 
member of your family. We will discuss the results with you so that you understand who else in your family could 
be a carrier for this same change. We can help arrange for this testing to be done, but the NIH cannot promise to 
perform or pay for the clinical testing necessary to confirm or determine who else in your family may have this 
change in their DNA. 
 
In addition to knowing what we could find, we would like you to know the limitations of the genome sequencing 
and what we will NOT be able to tell you about the changes that we find.  
 
1. Not all gene changes that cause disease will be detected.  
2. Some changes that are not currently known to cause health problems will be found to cause health problems 
in the future. We cannot promise to be able to tell you about those changes in the future.  
3. We will not tell you about gene changes that are not known to have health implications, nor will we tell you 
about gene changes that have only reproductive consequences.  
4. This gene sequencing cannot be substituted for diagnostic testing recommended by another physician.  
 
Emotional and psychological risks from DNA testing. Identification of gene changes could cause emotional 
and psychological problems. In some situations psychological counseling could be recommended. 
 
1. Learning about disease risk in your family can be distressing. 
2. Learning that you passed on a gene that does not work to your child can be distressing. 
3. Other members of your family could be upset to learn that they may be at risk for a disorder because of your 
participation in this study. 
 
You may be falsely reassured about your health status if we do not report any changes to you. 
 
Other risks of genetic testing. If we confirm a gene change in your DNA in a diagnostic laboratory, this 
information will become part of your medical record at the NIH. Some people are concerned that information 
about them from their medical records could be released. Possible problems include insurance or employment 
discrimination. Measures to protect the confidentiality of your information are described below. These problems 
may also occur if you disclose information yourself or agree to have your research records released. 
 
There are state and federal laws that protect against genetic discrimination. A federal law called the Genetic 
Information Nondiscrimination Act (GINA) generally makes it illegal for health insurance companies, group health 
plans, and most employers to discriminate against you based on your genetic information. According to this law, 
health insurance companies or group health plans (as of May 21, 2010) cannot request your genetic information 
or use it to make decisions about your eligibility or premiums; and employers cannot use it in deciding to hire, 
promote, or fire you or in setting the terms of your employment (as of Nov 21, 2009). 
 
Be aware that this Federal law does not protect you against genetic discrimination by companies that sell life 
insurance, disability insurance, or long-term care insurance. 
 
The following link contains details on this policy: 
http://www.genome.gov/Pages/PolicyEthics/GeneticDiscrimination/GINAInfoDoc.pdf 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 8 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
You may ask your research team for additional information or a copy of The Genetic Information 
Nondiscrimination Act of 2008 informational document. 
 
 
Use of stored samples and data 
 
Future DNA Research. Currently we plan to sequence known genes, which is only about 1% of your total DNA. 
In the future we may sequence other parts of your DNA, and it is possible that we will need to send your DNA to 
specialized labs outside of the NIH to do these tests.  If this is done, your DNA will be coded and will not have 
your name or any other personally identifying information on the sample. The outside lab will have no way of 
identifying that the blood sample came from you.   
 
Please initial one of the following three statements regarding future research: 
 
______  I give permission to perform future studies on my DNA without needing my additional consent. I 
understand I will not be contacted if these samples are used in the future. 
 
______  I must be contacted and give consent if my DNA samples are to be used in future research studies that 
are not described above in this consent form. 
 
______ Do not use my DNA for any future studies beyond those described above in this consent form. 
 
Future research with tissue samples. We plan to store some of your blood, urine, stool, and tissue samples in 
the freezer for future studies that are not specifically outlined in this consent form. It is possible that we will need 
to send your samples to specialized labs outside of the NIH to do these future tests. Also, these samples may be 
stored at a separate site (called a repository) that specializes in storing clinical samples. Any samples that leave 
our lab will be coded and kept anonymous, and the samples will not have your name or any other personally 
identifying information on them.  In addition, it is possible that some information obtained from these studies will 
be published in the medical literature. However, your identity will not be included in any publications. 
 
Please initial one of the following two statements: 
 
______ I understand that samples collected during these NIH visits will be saved and used for future 
experimental testing.  I authorize other uses of these samples without my additional consent. I 
understand I will not be contacted if these samples are used in the future. 
 
______ I understand that samples collected during these NIH visits will be saved and used for future 
experimental testing. I must be contacted and give additional consent if these samples are to be used in 
future studies not described above in this consent form. 
 
All through the process of the study and afterwards, the confidentiality of participants will be protected by using 
codes and medical record numbers in recording your information and test results. Only medical personnel involved 
in this study will have access to participants’ names, test results, and patient code numbers.  Should you 
withdraw from this study, we will keep your DNA and tissue for analysis unless you ask us to destroy the samples. 
You have the option, in the future, of requesting that these samples not be used for any additional testing. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 9 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
DNA Scientific Databases.  To do more powerful research, it is helpful for researchers to share information 
they get from studying human samples.  They do this by putting it into one or more scientific databases, where it 
is stored along with information from other studies.  This “larger pool” of information helps enable scientific 
breakthroughs.  
 
You need to be aware that DNA sequence is like a fingerprint. Theoretically if enough DNA sequence information 
is available, someone could identify you based on his/her DNA sequence. To facilitate genetic research, your DNA 
sequence information may be deposited in other databases. In this case, unless we have your permission, we will 
deposit the data in a manner that would not allow someone to identify you. Please understand that this 
information cannot be removed once it is deposited. 
 
Please initial one of the following statements: 
 
______ I do not want DNA sequence data to be deposited in any database other than the one associated with 
this study. 
 
______ My DNA sequence data can be deposited in databases that limit access to IRB (ethics board) approved- 
researchers. 
 
______ My DNA sequence can be deposited in a database that is available only to scientists but that does not 
require IRB approval of research studies. I understand that someone could theoretically identify me from 
this information. 
 
Potential benefits of participation 
 
We are hopeful that your participation in this study will help us better understand the mechanisms of how insulin works in 
the body.  However, you will not benefit directly from participating in this study.  Should we find abnormalities in any of 
your test results, you will be notified and receive a copy to assist you in seeking further medical evaluation. This 
information may or may not improve your health.  
 
Right of Withdrawal and Conditions for Early Withdrawal  
 
You may withdraw from the study at any time and for any reason without loss of benefits or privileges to which you are 
otherwise entitled.  
 
Discussion of New Findings with You 
 
There is no general plan to share your individual test results with you. However, if any findings suggest you have a 
medical issue, we will provide this information to you and your primary care provider. You may request a copy of your 
routine laboratory tests if you desire.  
 
Study Termination 
 
You may be asked to end your participation in this study at any time if we believe that continuation is not in your best 
medical interest or if you are unable to comply with the requirements of the study.  
 
 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page 10 of 11 pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Alternatives to Participation 
 
The alternative to this study is not to participate. You may be eligible for other studies in the NIH. You may learn more 
about them through www.clinicaltrials.gov. 
 
 
Compensation 
 
You will be compensated for the time and inconvenience associated with participation according to NIH research volunteer 
guidelines.  Compensation for completing all of the testing described above is $100 for the outpatient screening visit and 
$300 for the baseline visit.  The total amount you could receive for participation if you complete all parts of this study is 
$400. 
 
Conflict of Interest 
 
The NIH and members of this research team have no financial interest related to this research study.  
 
Posting of Research Results on www.ClinicalTrials.gov  
 
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This web site 
will not include information that can identify you. At most the Web site will include a summary of the results. You can 
search this Web site at any time. 
 
 
______  I have received a copy of the signed consent form. 
 
 
 
 


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  11  of  11  pages 
 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
OTHER PERTINENT INFORMATION 
 
1. Confidentiality.  When results of an NIH research study are reported in medical journals or at scientific meetings, 
the people who take part are not named and identified.  In most cases, the NIH will not release any information about 
your research involvement without your written permission.  However, if you sign a release of information form, for 
example, for an insurance company, the NIH will give the insurance company information from your medical record.  This 
information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance. 
 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you should know that the Act 
allows release of some information from your medical record without your permission, for example, if it is required by the 
Food and Drug Administration (FDA), members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
 
2. Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-term medical care for any 
injury resulting from your participation in research here.  In general, no long-term medical care or financial compensation 
for research-related injuries will be provided by the National Institutes of Health, the Clinical Center, or the Federal 
Government.  However, you have the right to pursue legal remedy if you believe that your injury justifies such action. 
 
3. Payments.  The amount of payment to research volunteers is guided by the National Institutes of Health policies.  In 
general, patients are not paid for taking part in research studies at the National Institutes of Health.  Reimbursement of 
travel and subsistence will be offered consistent with NIH guidelines. 
 
4. Problems or Questions.  If you have any problems or questions about this study, or about your rights as a research 
participant, or about any research-related injury, contact the Principal Investigator, Jack A. Yanovski, MD, PhD; Building 
10-CRC Room 1-3330, Telephone: 301-496-4686 or Associate Investigator Andrew Demidowich, MD; Building 10-CRC 
Room 1-3330, Telephone: 301-496-4686. 
 
You may also call the Clinical Center Patient Representative at 301-496-2626. 
 
5. Consent Document.  Please keep a copy of this document in case you want to read it again. 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby consent to take 
part in this study. 
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby give permission 
for my child to take part in this study.   
(Attach NIH 2514-2, Minor’s Assent, if applicable.) 
 
  
 
 
  
 
Signature of Adult Patient/Legal Representative 
Date 
 
 
 
Print Name 
Signature of Parent(s)/Guardian 
Date 
 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to participate in the study. 
 
 
 
  
 
 
 
 
Signature of Parent(s)/Guardian 
Date 
 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM JANUARY 24, 2018 THROUGH FEBRUARY 24, 2019. 
 
 
 
  
 
 
  
 
Signature of Investigator 
Date 
 
 
 
Print Name 
Signature of Witness 
Date 
 
 
 
Print Name 
 


 
 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
               • Adult Patient or     •  Parent, for Minor Patient 
 
 
INSTITUTE: 
Instituto Nacional de Salud Infantil y Desarrollo Humano (National Institute of Child Health and  
 
Human Development) 
 
 
STUDY NUMBER: 
14-CH-0119 
PRINCIPAL INVESTIGATOR:  Jack Yanovski, M.D. 
 
 
STUDY TITLE: 
Estudio preliminario de los efectos de la colchicina en adultos no diabéticos con síndrome 
metabólico 
 
Pilot Study of the Effects of Colchicine in Non-Diabetic Adults with Metabolic Syndrome) 
 
 
Continuing Review Approved by the IRB on 01/24/18 
Amendment Approved by the IRB on 07/13/18 (S)  
 
 
Date Posted to Web: 08/03/18 
Evaluation Only - Spanish 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY 
 
•   Adult Patient or    •   Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent (4) 
 
 
INTRODUCCIÓN 
 
Deseamos invitarle a participar en un estudio de investigación en los Institutos Nacionales de Salud (National Institutes of 
Health, NIH). 
 
En primer lugar, queremos que Ud. sepa que: 
La participación en una investigación del NIH es totalmente voluntaria. 
Usted puede decidir no participar o retirarse del estudio en cualquier momento. En cualquier caso, no perderá 
ninguna compensación a la que pueda tener derecho. No obstante, para recibir atención médica en el NIH usted 
debe participar en un estudio o estar en evaluación para participar en uno. 
 
Es posible que no reciba ningún beneficio por su participación. Con la investigación podemos adquirir 
conocimientos que ayuden a otras personas en el futuro. 
 
En segundo lugar, algunas personas pueden tener creencias personales, religiosas o éticas que limiten los tipos de 
tratamientos médicos o de investigación que deseen recibir (por ejemplo, transfusiones de sangre). Si usted es una de 
esas personas, hable al respecto con sus médicos o con el equipo de investigación del NIH antes de acceder a participar 
en el estudio. 
 
El estudio se describe en las siguientes páginas. Antes de decidir participar, tómese todo el tiempo que necesite para 
hacer preguntas y hablar del estudio con cualquier persona del NIH, o con su familia, amigos, médico personal o 
cualquier otro profesional de la salud.
 
Propósito de este Estudio 
 
Las células grasas desempeñan numerosos papeles importantes en nuestro cuerpo, incluyendo el almacenamiento de 
energía, la secreción de hormonas, y ayudando a regular nuestro metabolismo. La insulina es una hormona que circula 
por todo el cuerpo y se comunica con las células grasas y regula su función. Cuando la capacidad de la insulina para 
comunicarse con el resto del cuerpo comienza a fallar, la gente se vuelve "resistente a la insulina" y pueden llegar a 
desarrollar diabetes. Sin embargo, los detalles específicos de cómo funciona la insulina a nivel de la célula grasa son aún 
poco conocidos. A propósito de este estudio es comprender mejor el tiempo y los mecanismos detrás de las acciones de 
la insulina en las células de grasa, y posiblemente identificar nuevos factores de por qué algunas personas son más 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 2 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
propensas a desarrollar diabetes. Le pedimos que nos ayude a entender cómo funciona la insulina en el cuerpo al 
someterse a una serie de pruebas. No se le pedirá que tome el medicamento de estudio (colchicina).   
 
Los participantes del estudio tendrán que venir al Centro Clínico del NIH para dos consultas ambulatorias.  Es importante 
que los participantes llegen en ayunas (sin alimentos ni bebidas aparte de agua) a cada una de estas visitas. Los 
participantes serán compensados por su tiempo y cualquier inconveniente. 
 
Población de estudio 
  
Deseamos reclutar a adultos sanos y adultos con diabetes tipo 2 tratados sólo con dieta. 
  
Quién puede participar en este estudio 
 
Usted puede ser elegible para este estudio de investigación si es mayor de 18 años de edad; pesar menos de 450 libras, y 
que se encuentre en buen estado de salud general.  
 
Quienes no pueden participar en este estudio 
  
Usted no puede ser elegible para este estudio si tiene una enfermedad médica grave que pudiera interferir con las 
pruebas o mediciones del estudio, como enfermedades del corazón, riñón, hígado, pulmón, sangre, intestinal o 
enfermedades endocrinas o presión arterial alta no controlada. Las personas con diabetes tipo 2 que están tomando 
medicamentos o tienen hemoglobina A1c> 9%, no pueden participar.  Si usted está usando un medicamento que afecta 
el metabolismo del azúcar y la grasa o la absorción en su cuerpo, es posible que no sea elegible para participar. Tampoco 
son elegibles las mujeres que están embarazadas o lactando, o tienen intención de quedar embarazadas; las personas 
que han tenido un cambio de peso reciente superior al 3% del peso corporal total, han estado utilizando medicamentos 
para reducir el peso, han usado recientemente la colchicina, tener una alergia conocida a la colchicina, o utilizan 
productos de tabaco o nicotina (p. ej. e-cigarrillos), no serán reclutadas para este estudio.  Las personas con 
antecedentes de formación de queloides (que fácilmente desarrollan cicatrices en su piel después de una lesión) tampoco 
no pueden participar en este estudio. 
  
Procedimientos del estudio 
  
El estudio consta de dos visitas ambulatorias en el Centro Clínico: una visita para determinar elegibilidad y una 
visita inicial para estudiar su metabolismo. 
 
Visita Ambulatoria de Selección de Pacientes  
  
Esta visita tomará unas 3 horas para realizarse. Usted será visto en un día de semana en el Centro Clínico del NIH. Le 
pedimos permanecer en ayunas durante las 10 horas anteriores a su llegada a la clínica y no debe comer o beber nada, 
excepto agua por la mañana. Durante esta visita, vamos a realizar lo siguiente: 
  
1. Protocolo y firma del formulario de consentimiento. Vamos a repasar el estudio en detalle y a responder 
cualquier pregunta. El formulario de consentimiento debe ser firmado antes de poder tomar parte en el estudio. 
 
2. Historia médica completa y un examen físico, con el peso, la altura, y la medición de la presión arterial. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 3 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
3. Un ECG se realizará para examinar la función de su corazón. 
 
4. Los análisis de sangre en ayunas para asegurarse de que usted se encuentra en buen estado de salud. El 
análisis examinará el recuento de células de la sangre, función hepática y renal, niveles de colesterol, los niveles 
de azúcar e insulina en sangre, pruebas de función tiroidea, nivel de la inflamación, así como muestras de sangre 
de reserva para ser preservadas para poder examinar durante futuras investigaciónes. También realizaremos 
pruebas para determinar si usted tiene alguna diferencia en genes que pueden ser importantes para el 
metabolismo y el peso corporal. Además para buscar algunos genes que ya nosotros pensamos que son 
importantes para el peso corporal, vamos a utilizar nueva tecnología de secuenciación de DNA que se verá en 
todos los genes humanos que conocemos. Esto se conoce como “exome” y secuenciación del genoma. Esta 
nueva tecnología nos permite mirar el ADN en gran detalle. 
 
5. Recogida de muestras de orina para asegurarse de que sus riñones funcionan normalmente, que no está 
tomando cualquier droga ilícita, y una prueba de embarazo (para las mujeres en edad fértil). 
 
6. Prueba de tolerancia a la glucosa oral. Vamos a realizar una prueba para examinar si usted tiene diabetes, la 
llamamos prueba de tolerancia a la glucosa de 2 horas. Va a tomar una taza de agua con azúcar y luego se 
tomarán muestras 1 y 2 horas después para mirar su nivel de azúcar en la sangre. 
 
7. Absorciometría dual de rayos X (DEXA) para examinar su composición corporal. La prueba consiste en 
permanecer inmóvil sobre una mesa mientras una pequeña cámara pasa sobre su cuerpo. La dosis de los rayos X 
es mucho menor que la cantidad que se obtiene de una radiografía de pecho normal. La cantidad total de tiempo 
para realizar esta prueba será de unos 20 a 30 minutos. 
 
Visita Inicial 
  
Si reúne los requisitos para participar en el estudio, se le cita para la visita inicial. Le pediremos que permanezca en 
ayunas durante 10 horas antes de llegar a la clínica y no comer o beber nada, excepto agua por la mañana. Usted será 
visto en un dia entre semana en el Centro Clínico de los Institutos Nacionales de Salud, y la visita tomará alrededor de 8 
horas para completarse. Durante esta visita vamos a realizar lo siguiente:  
 
1. Intervalo de historia clínica y examen físico, con el peso, la altura, y la medición de la presión 
arterial. También se completará un cuestionario. 
 
2. Los análisis de sangre en ayunas para mirar su metabolismo basal y los niveles inflamatorios, así como 
muestras de sangre de reserva para ser preservados para las pruebas de investigación adicionales posibles, 
incluyendo una muestra para futuro análisis genético. Vamos a insertar una pequeña aguja en la vena (una vía 
intravenosa o IV) con el fin de obtener las muestras de sangre. 
 
3. Obtención de muestras de heces, obtendremos dos muestras de heces para conservar para futuros 
experimentos. Como parte de esta colección, le pediremos que mantenga un record de su dieta por 24 horas en 
un formulario que se le entregara a usted, y asi ver como la dieta puede afectar los resultados de las pruebas de 
heces. Los resultados de este “diario de nutricion” irá con un nutricionista. 
 
4. Obtención de muestras de orina como se describe antes. También vamos a recoger la orina durante su visita a 
ahorrar para futuros experimentos. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 4 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
5. Prueba de tolerancia a la glucosa intravenosa muestreado frecuentes.  Este estudio nos dice mucho 
acerca de cómo su cuerpo utiliza el azúcar, qué tan bien está funcionando su insulina y cómo es la sensibilidad de 
su cuerpo a la insulina. El estudio FSIVGTT se hace mientras usted descansa en una cama. Una segunda línea IV 
se coloca en su brazo. Le daremos un poco de agua de azúcar en una vía intravenosa durante un período de 2 
minutos. Entonces vamos a tomar muestras de sangre de la otra IV en -15, -10, -5, -1, 2, 3, 4, 5, 6, 8, 10, 14, 
19, 22, 25, 30, 40, 50, 70, 100, 140, y 180 minutos (un total de 3 horas ) para medir los niveles de azúcar e 
insulina . Exactamente a los 20 minutos en la prueba, le daremos una pequeña cantidad de insulina a través de la 
IV. Un médico o enfermera practicante estará presente durante la primera hora del estudio. Usted puede ver la 
televisión durante esta prueba. 
 
6. Tomografía Computarizada (TC) del abdomen para observar donde se tiende a almacenar su grasa. La 
prueba consiste en permanecer quieto en una mesa móvil que pasa por un gran anillo donde esta ubicada la 
cámara. La prueba implica radiación, pero solo porque tomaremos una foto de su abdomen, el método que se 
utilizará minimiza su exposición. La cantidad total de tiempo para realizar esta prueba será de unos 20 a 30 
minutos 
 
7. Subcutánea Biopsia de grasa. Para examinar el nivel de ciertas moléculas en el tejido graso, se tomará una 
pequeña muestra de tejido graso de debajo de la piel de su abdomen. Para adormecer el área donde se tomarà 
la muestra, se utilizará la lidocaína, un anestésico local. Una aguja se utilizará para extraer una porción de tejido 
graso que mide alrededor de 1 ½ cucharaditas. Un vendaje se aplica entonces al sitio de inserción de la aguja. 
Podemos darle algún medicamento para el leve dolor, como Tylenol o medicamento más fuerte si es necesario, 
después de la biopsia. La biopsia se tomará de un lugar del cuerpo que normalmente está cubierto y que no se 
ve fácilmente. 
 
Cuando el estudio se haya completado, volverá al cuidado de su médico de cabecera. La participación en este estudio no 
compromete al NIH a su cuidado a largo plazo. 
  
Los resultados de pruebas realizadas en el NIH 
  
Estaremos midiendo muchas cosas en su sangre durante sus visitas, y podríamos descubrir algún problema médico que 
requiere tratamiento. Ud. no recibirá de forma rutinaria tratamiento para cualquier condición de salud descubierto. Sin 
embargo, se le informará sobre estos hallazgos (por ejemplo: presión arterial alta) y cualquier información de importancia 
médica que resulten de análisis de sangre o del examen físico, serán remitidos a su médico de atención primaria en su 
solicitud. Algunos de estos problemas médicos podrían impedir su participación más en el estudio. 
 
Riesgos y molestias 
  
1. El examen físico. Un médico o una enfermera puede tener que le examinar pidiéndole que se quite su ropa, 
con las precauciones adecuadas para proteger su privacidad. Algunos pueden encontrar este examen vergonzoso. 
 
2. Exposición a la radiación: Este estudio de investigación implica la exposición a la radiación de tres imagenes 
DEXA y tres tomografías computarizadas. Tenga en cuenta que esta exposición a la radiación no es necesario 
para su atención médica y es sólo para fines de investigación. El Comité de Seguridad Radiológica NIH ha 
revisado el uso de la radiación en este estudio de investigación y ha aprobado este uso ya que implica un riesgo 
mínimo y necesario para obtener la información de investigación deseada.  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 5 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Aunque cada órgano recibirá una dosis diferente, la cantidad de exposición a la radiación que recibirá anualmente 
de este estudio es igual a una exposición uniforme de todo el cuerpo a 0.031 rem. Este valor calculado se conoce 
como la "dosis efectiva" y se utiliza para relacionar la dosis recibida por cada órgano a un solo valor. La cantidad 
de radiación que recibirá en este estudio es inferior a la pauta de dosis establecido por el Comité de Seguridad 
Radiológica NIH para los sujetos de investigación. Esta pauta establece una dosis efectiva de 5 rem recibido por 
año. 
 
Por comparación, la persona promedio en los Estados Unidos recibe una exposición a la radiación de 0,3 rem por 
año a partir de fuentes naturales, como el sol, el espacio exterior, y de materiales radiactivos que se encuentran 
naturalmente en el aire y el suelo. Si desea más información sobre la radiación y los ejemplos de los niveles y 
forma de exposicion a otras fuentes, por favor pregunte al investigador para obtener una copia del folleto 
titulado, An Introduction to Radiation for NIH Research Subjects. 
 
3. La extracción de sangre. La cantidad de extracción de sangre es muy por debajo de la directriz del NIH para 
una cantidad segura de extracción de sangre (550 cc cada 8 semanas). Un pequeño moretón se puede formar en 
cualquier sitio donde se toma la sangre. El riesgo de infección o desmayo es muy pequeña. La inflamación o 
coagulación de una vena también pueden ocurrir raramente. 
 
Una parte de su sangre será enviada a otros laboratorios dentro del NIH para examinar sus niveles de 
inflamación. Las muestras serán codificadas, y sólo los investigadores de este estudio tendrán acceso a la 
identidad de las muestras 
 
4. Recogida de muestras de heces no tiene ningún riesgo, y sólo debe tomar un momento para recogerlas. Las 
muestras serán codificadas, y sólo los investigadores de este estudio tendrán acceso a la identidad de las 
muestras. 
 
5. La recogida de muestras de orina no tiene ningún riesgo y sólo toma un momento para completar. Si el 
resultado es positivo para una sustancia ilícita, el resultado será parte de su expediente médico NIH. 
 
6. Los cuestionarios no son peligrosos, pero pueden ser un inconveniente debido al tiempo necesario para su 
realización.  
 
7. Prueba oral de tolerancia a la glucosa. Esta prueba es un inconveniente debido al tiempo que se tarda en 
completar. Los únicos riesgos de este tipo de estudio son las descritos para cualquier extracción de sangre, así 
como el desarrollo de las náuseas por la glucosa oral. Algunos pacientes pueden desarrollar de forma transitoria 
niveles altos de azúcar en la sangre a partir de la glucosa, pero deben normalizarse a las pocas horas y no deben 
ser clínicamente significativos. 
 
8. Prueba de tolerancia a la glucosa intravenosa. Esta prueba es un inconveniente debido al tiempo que se 
tarda en completar. Usted puede ver la televisión durante esta prueba. Los únicos riesgos de este tipo de 
estudios son las descritas para cualquier extracción de sangre, la posibilidad de una ligera sensitividad en el brazo 
al recibir la infusión de azúcar, (esa sensitividad desaparece al cabo de unos minutos con el roce suave del 
brazo), y la posibilidad de un bajo nivel de azúcar en la sangre durante el estudio. Cuando la azúcar en sangre 
esta baja (menos de 50 mg/dl), los participantes pueden tener hambre, tener dolor de cabeza, sentirse 
temblorosos o mareados o pueden llegar a ponerse sudorosos. Con azúcar en la sangre muy bajos (menos de 30 


 
  
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CONTINUATION:  page 6 of 13 pages 
 
 
 
 
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mg /dl) participantes pueden tener problemas para hablar, dificultad para despertar, e incluso tener convulsiones.  
 
Sin embargo, en la prueba que estamos haciendo, le estaremos dando azúcar extra para elevar el azúcar en la 
sangre por encima de lo normal, y luego vamos a tratar de traerlo de vuelta a la normalidad (95-105 mg / dL) 
con insulina. Para ello, vamos a medir el azúcar en la sangre a los 2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 24, 27, 30, 40, 
50, 70, 90, 120, 140, 160, y 180 minutos (un total de 3 horas). Un médico o enfermera practicante estará 
presente durante la primera hora de su prueba para asegurarse de que todo funciona correctamente. Esperamos 
que la posibilidad de un nivel de azúcar en sangre bajo sea muy pequeña. Si un bajo nivel de azúcar en la sangre 
no sube por sí sola con rapidez, se detendrá la prueba y se le dará el azúcar por vía IV para elevar el azúcar en la 
sangre a la normalidad 
 
9. Biopsias de grasa. Los posibles efectos secundarios de la biopsia son el dolor durante y durante dos o tres días 
después del procedimiento. Aunque rara vez, la zona de la biopsia puede estar sensible o adolorida o tener 
moretones o hinchazón durante 2-3 semanas. Heridas biopsia suelen sanar con una cicatriz muy pequeña, casi 
imperceptible, pero a veces una cicatriz elevada (queloides) o bulto visible puede resultar. Su riesgo es 
ligeramente mayor si usted es afroamericano. Inyección de lidocaína para adormecer antes de biopsias de grasa 
puede causar un poco de ardor suave antes de que llegue el entumecimiento. Efectos adversos raros incluyen la 
infección en los sitios de biopsia o una reacción alérgica a la lidocaína que puede llevar a una erupción y/o 
hinchazón de la zona de inyección. Si usted sabe que es alérgico a la lidocaína, cambiaremos a otro anestésico 
local. Otro de los riesgos del procedimiento es sangrado menor en el área de la biopsia. Algunos medicamentos 
pueden aumentar la cantidad de sangrado de la biopsia. Si está tomando medicamentos como Coumadin, Plavix 
o aspirina para adelgazar la sangre, usted no tendrá una biopsia. Si está tomando aspirina o medicamentos no 
esteroides como Advil para el dolor tendrá que dejar de tomar estos medicamentos durante una semana antes de 
realizar la biopsia. 
 
10. Las pruebas de ADN. Si nos permite estudiar su ADN, lo vamos a utilizar para la secuenciación del genoma. La 
secuenciación del genoma es una prueba que nos podrían dar diferentes tipos de resultados. Estos incluyen: 
a. Podríamos identificar cambios en los genes que están relacionados con el metabolismo y el peso corporal.  
b. Podríamos identificar cambios en los genes que contribuyen a otras enfermedades o problemas. 
c. Podríamos identificar los cambios en los genes que no son conocidos por causar ninguna enfermedad. Estos 
son conocidos como variaciones normales. 
d. Podríamos encontrar cambios en los genes que son nuevos y de importancia clínica incierta. Esto significa 
que no se sabe si podrían causar o contribuir a una enfermedad o si son variaciones normales. 
  
Uno de los objetivos de este estudio es identificar los cambios en los genes que pueden estar implicados en la 
obesidad. Esta investigación puede tomar años. Sin embargo, si se identifica una causa genética o la causa 
probable de la obesidad, con su permiso, nos pondremos en contacto con usted. Por favor, háganos saber su 
preferencia con sus iniciales en una de estas dos declaraciones: 
  
______  Me gustaría ser contactado con la información sobre los avances de este estudio y contactado 
acerca de cualquier resultado relacionado con la obesidad. Entiendo que esta investigación 
llevará años y que una anormalidad específica no se puede identificar en mí. 
  
______  Por favor no se contacte conmigo acerca de la marcha de este estudio o cualquier cambio de 
genes específicos relacionados con la obesidad.  
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 7 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
______  Yo no autorice ninguna muestras genéticas que se recojan durante estas visitas NIH. 
  
La identificación de cambios genéticos que no están relacionados con la condición que se está estudiando, se 
conoce como información médica incidental.  Vamos a encontrar cambios genéticos en todo el mundo que 
estudiamos, pero estamos mirando sólo específicamente para los genes relacionados con el metabolismo y el 
peso corporal.  Aun así, algunos cambios en los genes no relacionados con el metabolismo y el peso corporal se 
detectarán. 
  
Nosotros sólo le informaremos de los cambios que tienen importancia médica urgente y se beneficiarían de 
un tratamiento médico temprano. Un ejemplo de esto sería un cambio en el gen que causa cáncer y en la que se 
beneficiaría de la detección temprana. No le informará de todos los cambios en los genes que tienen inciertas 
implicaciones para la salud.  No vamos a informar de los cambios genéticos que predisponen a los individuos sólo 
a la enfermedad. Un ejemplo de esto sería un cambio en el gen que influye en el riesgo de enfermedades del 
corazón, pero en el que el desarrollo de la enfermedad depende de muchos factores genéticos y no genéticos 
(tales como la dieta y el tabaquismo).  Además, no le informaremos de cambios genéticos que pueden tener 
consecuencias reproductivas, tales como la impotencia o infertilidad. 
 
Si detectamos un cambio genético que podría ser importante para usted, sólo le daremos los resultados si el 
cambio ha sido confirmado por un laboratorio certificado.  Por esta confirmación, le pediremos una nueva 
muestra de ADN a usted. En la mayoría de los casos esto implicará la obtención de una pequeña muestra de 
sangre (1-2 cucharaditas). A veces podemos obtener suficiente ADN para confirmar su cambio genético al golpear 
el interior de la mejilla. 
 
Una vez que se confirma un cambio en un gen, vamos a discutir los resultados con usted y hacer 
recomendaciones sobre apropiado seguimiento médico. El NIH no puede prometer realizar o pagar por los 
exámenes médicos recomendados o evaluaciones.  Es posible que un cambio genético no se confirmará en las 
pruebas posteriores. Esto podría ser debido a un error en la secuenciación de ADN o un error en el procesamiento 
del ADN o líneas celulares. Aunque es agradable para Ud. que no se confirme el problema, esto puede causar un 
poco de ansiedad y preocupación que de otra manera no habría experimentado. 
  
Por favor, háganos saber sus preferencias colocando sus iniciales en una de las siguientes afirmaciones: 
  
______ Yo QUIERO ser re-contactado si se descubren variantes genéticas con consecuencias urgentes 
para la salud, durante esta prueba de investigación. 
  
______ NO deseo volver a ser contactado si se descubren variantes genéticas con consecuencias 
urgentes para la salud durante esta prueba de investigación.  
 
Si usted tiene un cambio en un gen con urgentes implicaciones para la salud, el NIH confirmará el cambio 
genético presente en uno de los miembros de su familia. Discutiremos los resultados con usted para que pueda 
saber si alguien más en su familia podría ser un portador de este mismo cambio. Podemos ayudarle a organizar 
las pruebas que haya que hacer, pero el NIH no podemos prometer realizar o pagar por las pruebas clínicas 
necesarias para confirmar o determinar quién más en su familia puede tener este cambio en su ADN. 
 
Además de saber lo que encontramos, nos gustaría que conociera las limitaciones de la secuenciación del 
genoma y lo que no vamos a ser capaces de decirle acerca de los cambios que encontramos. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 8 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
  
1. No todos los cambios en los genes que causan la enfermedad serán detectados. 
2. Algunos de los cambios que no se conocen actualmente para causar problemas de salud podrían causar 
problemas de salud en el futuro. No podemos prometer tener la capacidad de decirle a usted acerca de esos 
cambios en el futuro. 
3. No le dirá acerca de cambios en los genes que no se sabe que tienen consecuencias para la salud, ni vamos a 
informarle sobre cambios en los genes que sólo tienen consecuencias reproductivas. 
4. Esta secuenciación de genes no puede ser sustituido por las pruebas de diagnóstico recomendado por otro 
médico. 
   
Riesgos emocionales y psicológicos de la prueba de ADN. La identificación de los cambios en los genes 
puede causar problemas emocionales y psicológicos. En algunas situaciones, se podría recomendar asesoría 
psicológica. 
  
1. Aprender sobre el riesgo de enfermedad que en su familia puede ser angustiante. 
2. Aprender que algo que sucede en un gen suyo, puede no suceder en su hijo, puede ser angustiante. 
3. Otros miembros de su familia podrían ponerse molestos al saber que ellos pueden estar en riesgo de un 
trastorno debido a su participación en este estudio. 
  
Ud. Puede permanecer falsamente tranquilo acerca de su estado de salud si nosotros no le reportamos ningún 
cambio en su caso. 
 
Otros riesgos de las pruebas genéticas. Si confirmamos un cambio genetico en su ADN en un laboratorio de 
diagnóstico, esta información será parte de su expediente médico en el NIH. Algunas personas se preocupan de 
que la información acerca de ellos de sus registros médicos podrían ser dadas a conocer. Posibles problemas 
incluyen el seguro o la discriminación laboral. Medidas para proteger la confidencialidad de su información  se 
describen a continuación. Estos problemas también pueden ocurrir si usted divulga su propia información o 
acepta que sus registros de investigación sean liberados. 
  
Hay leyes estatales y federales que protegen contra la discriminación genética. Una ley federal llamada la Ley de 
No Discriminación por información Genética (GINA), generalmente hace que sea ilegal que las compañías de 
seguros de salud, planes de salud de grupo, y la mayoría de los empleadores discriminen contra usted basado en 
su información genética. Según esta ley, las compañías de seguros de salud o planes de salud de grupo (hasta el 
21 de mayo de 2010) no puede solicitar su información genética, o utilizarlo para tomar decisiones sobre su 
elegibilidad o primas; y los empleadores no pueden utilizarlo en la decisión de contratar, promover, ni puede 
despedirlo, o en el establecimiento de los términos de su empleo (a fecha de 21 de noviembre 2009). 
  
Tenga en cuenta que esta ley federal no le protege contra la discriminación genética por las compañías que 
venden seguros de vida, seguro de invalidez, o un seguro de cuidado a largo plazo. Este enlace contiene detalles 
sobre esta política: http://www.genome.gov/Pages/PolicyEthics/GeneticDiscrimination/GINAInfoDoc.pdf 
  
Usted puede preguntar a su equipo de investigación para obtener información adicional o una copia de la Ley de 
No Discriminación por Información Genética de 2008 documento informativo. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 9 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
El uso de muestras almacenadas y datos 
  
Investigaciones futuras ADN. Actualmente tenemos la intención de secuenciar los genes conocidos, que 
representa sólo alrededor del 1% de su secuencia de ADN. En el futuro podemos secuenciar otras partes de su 
ADN, y es posible que pueden ser enviadas a otros laboratorios para pruebas específicas. Si esto se hace el ADN 
será codificado y no tendrá su nombre o cualquier otra información de identificación personal en la muestra. El 
laboratorio externo no tendrá manera de identificar que la muestra de sangre provenía de ti. 
  
Por favor, coloque su inicial en una de las siguientes tres declaraciones relativas a la investigación futura: 
 
______ Yo doy permiso para realizar futuros estudios sobre mi ADN sin necesidad de mi consentimiento 
adicional. Entiendo que no se pondrá en contacto si se utilizan estas muestras en el futuro. 
  
______ Debo ser contactado y dar consentimiento si estas muestras se van a utilizar en futuros estudios de 
investigación que no se describen más arriba en este formulario de consentimiento. 
  
______ No utilice mi ADN para futuros estudios más allá de los descritos anteriormente en este formulario de 
consentimiento. 
  
Futuras investigaciones con muestras. Tenemos la intención de almacenar algunos muestras de su sangre, 
orina, heces, y tejidos en el congelador para futuros estudios que no se describen específicamente en este 
formulario de consentimiento. Es posible que necesitáramos para enviar sus muestras a laboratorios 
especializados fuera del NIH para hacer estas pruebas futuras. Además, estas muestras pueden almacenarse a un 
sitio separado (llamado un repositorio) que se especializa en el almacenamiento de muestras clínicas. Cualquier 
muestra que dejan nuestro laboratorio serán codificados y se mantiene en el anonimato, y las muestras no 
tendrán su nombre o cualquier otra información de identificación personal sobre ellos. Además, es posible que 
alguna información obtenida de estos estudios serán publicados en la literatura médica. Sin embargo, su 
identidad no será incluida en cualquier publicación. 
 
Por favor, coloque su inicial en una de las dos afirmaciones siguientes: 
  
______ Entiendo que las muestras recogidas durante estas visitas NIH serán guardadas y utilizadas para futuros 
ensayos experimentales.  Autorizo a otros usos de estas muestras sin mi consentimiento adicional. 
Entiendo que no se pondrán en contacto si se utilizan estas muestras en el futuro. 
  
______ Entiendo que las muestras recogidas durante estas visitas NIH serán guardadas y utilizadas para futuros 
ensayos experimentales. Debo ser contactado y dar consentimiento si estas muestras se van a utilizar en 
en futuros estudios no descritas anteriormente en este formulario de consentimiento. 
  
Durante todo el proceso de estudio y después, la confidencialidad de los participantes será protegida mediante el 
uso de códigos y números de historia clínica en la grabación de su información y resultados de pruebas. Sólo el 
personal médico involucrado en este estudio tendrán acceso a los nombres de los participantes, resultados de 
exámenes, y los números de código de los pacientes.  En caso de retirarse de este estudio, vamos a mantener su 
ADN para el análisis a menos que usted nos pida destruir las muestras de ADN.  Usted tiene la opción, en el 
futuro, de solicitar que estas muestras no se pueden usar para cualquier prueba adicional. 
 
Bases de datos científicos de ADN. Para hacer la investigación más potente, es de gran ayuda para los 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 10 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
investigadores compartan la información que reciben de estudio de muestras humanas. Lo hacen mediante la 
puesta en una o más bases de datos científicas, donde se almacena junto con la información de otros estudios. 
Este "grupo más grande" de la información ayuda a permitir avances científicos. 
  
Usted tiene que ser consciente de que la secuencia de ADN es como una huella digital. Teóricamente si suficiente 
información de la secuencia de ADN está disponible, alguien podría identificarlo a Ud. en base a su secuencia de 
ADN. Para facilitar la investigación genética, la información de su secuencia de ADN se puede depositar en otras 
bases de datos. En este caso, a menos que tengamos su permiso, vamos a depositar los datos de una manera 
que no permita que alguien le identifique. Por favor, comprenda que esta información no se puede eliminar una 
vez que se deposita. 
   
Por favor, coloque su inicial en una de las siguientes casillas: 
  
______ No quiero que los datos de secuencia de ADN sean depositados en cualquier base de datos que no sea la 
que está asociada con este estudio. 
 
______ Mis datos de secuencias de ADN pueden ser depositados en las bases de datos que limitan el acceso a la 
IRB (comité de ética) Investigadores aprobados. 
  
______ Mi secuencia de ADN puede ser depositada en una base de datos que está disponible sólo para los 
científicos, pero que no requiere la aprobación del IRB de estudios de investigación. Entiendo que alguien 
teóricamente me podía identificar de esta información. 
  
Los beneficios potenciales de la participación 
 Tenemos la esperanza de que su participación en este estudio nos ayudará a comprender mejor los mecanismos de 
cómo funciona la insulina en el cuerpo. Sin embargo, no se beneficiará directamente de participar en este estudio.  Al 
encontrar anomalías en cualquiera de sus resultados de la prueba, se le notificará y recibirá una copia para ayudarle en la 
búsqueda de una mayor evaluación médica. Esta información puede o no mejorar su salud.   
  
Derecho de revocación y Condiciones de retiro anticipado 
 
Usted puede retirarse del estudio en cualquier momento y por cualquier motivo y sin pérdida de beneficios o privilegios a 
los que tiene derecho. 
  
La discusión de los nuevos hallazgos con usted 
 
No hay plan general para compartir los resultados de sus pruebas individuales con usted. Sin embargo, si algún hallazgo 
sugiere que tiene un problema médico, vamos a proporcionar esta información a usted y a su proveedor de atención 
primaria. Usted puede solicitar una copia de sus pruebas de laboratorio de rutina si lo desea. 
  
Terminación de Estudios 
 
Es posible que terminamos su participación en este estudio en cualquier momento, si creemos que la continuación en él 
no es lo mejor para su interés médico o si no puede cumplir con los requisitos del estudio. 
  
Alternativas a la Participación 
 
La alternativa a este estudio es no participar. Usted puede ser elegible para otros estudios en los NIH. Usted puede 
aprender más sobre ellos a través de www.clinicaltrials.gov. 
  
Compensación 
Usted será compensado por el tiempo y los inconvenientes asociados a la participación según las directrices de 
compensación para voluntarios de investigación del NIH. La compensación para completar todas las pruebas que se han 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 11 of 13 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
descrito anteriormente es: $100 por la Visita Ambulatoria de Selección de Pacientes, y $300 por la Visita Inicial.  La 
cantidad total que usted podría recibir por la participación si completa todas las partes de este estudio es de $400. 
  
Conflicto de intereses 
El NIH y los miembros de este equipo de investigación no tienen ningún interés financiero en relación con este estudio de 
investigación. 
  
 
Publicación de Resultados de Investigación en: www.ClinicalTrials.gov 
Una descripción de este ensayo clínico estará disponible en http://www.Clinicaltrials.gov, como lo requiere la ley de 
Estados Unidos. En esta pagina de web no incluirá información que pueda identificarlo. En la mayor parte del sitio Web 
incluirá un resumen de los resultados. Usted puede buscar en este sitio web en cualquier momento. 
  
 
______ He recibido una copia del formulario de consentimiento firmado. 


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 12 of 13 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
INFORMACIÓN PERTINENTE ADICIONAL 
 
1. Confidencialidad. Cuando los resultados de un estudio de investigación del NIH se dan a conocer en revistas 
médicas o reuniones científicas, no se menciona la identidad de los participantes. En la mayoría de los casos, el NIH no 
divulgará ninguna información sobre su participación en la investigación a menos que usted otorgue su permiso por 
escrito. No obstante, si usted firma una autorización de divulgación de información, por ejemplo, a una empresa 
aseguradora, el NIH le proporcionará a ésta información de su expediente médico. Esta información podría influir (en 
forma favorable o desfavorable para usted) la disposición de la aseguradora a venderle el seguro.  
 
La Ley Federal de Protección de la Vida Privada (Federal Privacy Act) protege el carácter confidencial de sus expedientes 
médicos en el NIH. Sin embargo, es importante que sepa que esta ley permite la divulgación de cierta información de su 
expediente médico sin su autorización, por ejemplo, si lo solicitan la Administración de Alimentos y Medicamentos (FDA), 
los miembros del Congreso, los agentes encargados del cumplimiento de la ley o las organizaciones autorizadas para 
efectos de acreditación hospitalaria.  
 
2. Normas sobre lesiones relacionadas con la investigación. El Centro Clínico le dará atención médica a corto 
plazo para cualquier lesión que se deba a su participación en una investigación que se realice allí. En general, ni los 
Institutos Nacionales de Salud, ni el Centro Clínico, ni el gobierno federal le darán atención médica a largo plazo ni 
indemnización económica por lesiones relacionadas con la investigación. Sin embargo, usted tiene derecho a buscar una 
compensación legal si cree que la lesión justifica dicha medida.  
 
3. Pagos. El monto del pago que reciben los voluntarios de investigación se rige por las normas de los Institutos 
Nacionales de Salud. En general, a los pacientes no se les paga por participar en los estudios de investigación en los 
Institutos Nacionales de Salud. Se le ofrecerá el reembolso de gastos de viaje y viáticos según las pautas del NIH.  
 
4. Problemas o preguntas. Si hay algún problema o usted tiene una pregunta con respecto a este estudio, a sus 
derechos como participante en un estudio de investigación clínica o a cualquier lesión relacionada con la investigación, 
debe comunicarse con el Investigador Principal, Jack A. Yanovski, MD, PhD; Building (Edificio) 10, Room (Sala) 1-3330, 
Teléfono: (301) 496-4686 o el Investigador Asociado Principal, Andrew Demidowich, MD; Building 10, Room 1-3330, 
Teléfono: (301) 496-4686.  
 
También puede llamar al representante de los pacientes del Centro Clínico, al teléfono (301) 496-2626.  
 
5. Documento de consentimiento. Le sugerimos que conserve una copia de este documento para consultarla 
posteriormente. 


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
 
CONTINUATION:  page 13 of 13 pages 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
 
 
COMPLETE LAS CASILLAS CORRESPONDIENTES A CONTINUACIÓN: 
 
A. Consentimiento de un paciente adulto. 
B. Permiso otorgado por el (los) padre(s) de un paciente 
menor de edad. 
He leído la explicación relacionada con este estudio y he tenido la 
oportunidad de comentarla y hacer preguntas. Por este medio otorgo mi 
consentimiento para participar en este estudio. 
He leído la explicación relacionada con este estudio y he tenido la 
oportunidad de comentarla y hacer preguntas. Por este medio otorgo 
permiso para que mi hijo participe en este estudio. 
(Anéxese el formulario NIH 2514-2, Asentimiento de un menor de edad, 
si corresponde.) 
 
  
 
 
  
 
Firma del paciente adulto o su representante  legal       Fecha 
 
 
 
Nombre en letra de imprenta 
Firma del (los) padre(s) o del tutor legal 
Fecha 
 
 
 
Nombre en letra de imprenta 
C. Asentimiento verbal de un niño (si corresponde)  
Se le explicó a mi hijo la información contenida en el presente documento y mi hijo está de acuerdo en participar en el estudio. 
 
 
 
  
 
 
 
 
Firma del (los) padre(s) o del tutor legal 
Fecha  
Nombre en letra de imprenta 
EL USO DE ESTE DOCUMENTO DE CONSENTIMIENTO ESTÁ APROBADO 
DESDE EL 24 DE ENERO DE 2018 HASTA EL 24 DE FEBRERO DE 2019.  
 
 
 
 
  
 
 
  
 
Firma del Investigador 
Fecha 
 
 
 
Nombre en letra de imprenta 
Firma del testigo 
Fecha 
 
 
 
Nombre en letra de imprenta 
 


 
 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
               •  Adult Patient or     •  Parent, for Minor Patient 
 
 
INSTITUTE: 
National Institute of Child Health and Human Development 
 
 
STUDY NUMBER: 
14-CH-0119 
PRINCIPAL INVESTIGATOR:  Jack Yanovski, M.D. 
 
 
STUDY TITLE: 
Pilot Study of the Effects of Colchicine in Non-Diabetic Adults with Metabolic Syndrome 
 
 
Continuing Review Approved by the IRB on 01/24/18 
Amendment Approved by the IRB on 07/13/18 (S)  
 
 
Date Posted to Web: 08/03/18 
Open-Label Arm 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY 
 
•   Adult Patient or    •   Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent (5) 
 
 
INTRODUCTION 
 
We invite you to take part in a research study at the National Institutes of Health (NIH). 
 
First, we want you to know that: 
 
 
Taking part in NIH research is entirely voluntary. 
 
 
You may choose not to take part, or you may withdraw from the study at any time.  In either case, you will not 
lose any benefits to which you are otherwise entitled.  However, to receive care at the NIH, you must be taking 
part in a study or be under evaluation for study participation. 
 
 
You may receive no benefit from taking part.  The research may give us knowledge that may help people in the 
future. 
 
Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research treatments 
they would want to receive (such as blood transfusions).  If you have such beliefs, please discuss them with your NIH 
doctors or research team before you agree to the study. 
 
Now we will describe this research study.  Before you decide to take part, please take as much time as you need to ask 
any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other 
health professional. 
 
 
Purpose of this Study 
 
Approximately 30% of adults in the US have a body mass index (BMI) over 30 kg/m2, and are at greater risk for a 
number of medical problems, including high blood pressure, high blood cholesterol, high triglyceride levels, high blood 
sugar (diabetes) and heart disease.  It is thought that being overweight leads to a state of low-level inflammation and 
this inflammation may actually lead to some of the medical problems associated with obesity.  The purpose of this study 
is to find out if a medication called colchicine can improve metabolism in adults who have medical complications of their 
high body weight (these complications are sometimes called the “metabolic syndrome”), and who have developed high 
blood sugar (diabetes). 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  2  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Colchicine is an anti-inflammatory medication that has been used for centuries in the treatment of gout.  From animal 
studies and human studies there is some evidence that anti-inflammatory medicines like colchicine may improve the 
pancreas’s ability to secrete insulin and the body’s ability to regulate sugar.  We ask you to join our study, so we can find 
out whether colchicine can improve sugar regulation and metabolic parameters. 
 
If you qualify and agree to participate, you will be one of seven people with Type 2 Diabetes (T2DM) assigned to take 
colchicine tablets by mouth twice a day for 3 months.  The colchicine tablets will come in the same dose that is available 
in pharmacies and is prescribed for a disease called “gout”: 0.6 milligrams.   
 
When the study is completed, we will send all participants information about the results, and tell them if taking colchicine 
helped improve their metabolic syndrome or diabetes. 
 
Study participants will need to come to the NIH Clinical Center for four outpatient visits, with an optional fifth outpatient 
visit. It is important that participants arrive fasting (no food or beverages besides water) to each of these visits.  
Participants will be compensated for their time and inconvenience (see below: Compensation on page 5). 
 
Study Population 
 
We wish to recruit seven overweight adults with diet-controlled T2DM. 
 
Who Can Be in This Study 
 
You may be eligible for this research study if you are greater than 18 years old, have a body mass index that is at least 
30 kg/m2 (calculated by dividing weight in kg by height in meters squared), weigh less than 450 lbs, and are in good 
general health. You also have to meet certain levels for insulin resistance and inflammation, as measured by lab testing, 
and have type 2 diabetes managed with diet to participate in the full study. If you are a woman of child-bearing age, 
you will be asked to use an effective form of birth control before participating in this study. 
 
Who May Not Be In This Study 
 
You may not be eligible for this study if you have a major medical illness that would interfere with study tests or 
measurements, such as heart, kidney, liver, lung, blood, gut, or endocrine diseases, or uncontrolled high blood 
pressure. If you are currently using a medication that affects sugar and fat metabolism or absorption in your body, or a 
medicine that should not be taken with colchicine, you may not be eligible to participate. Also individuals who are 
pregnant or nursing, or planning to become pregnant, have had a recent weight change greater than 3% of total body 
weight, have been using weight reducing medications, have recently used colchicine, have a known allergy to 
colchicine, or use tobacco or nicotine (e.g. e-cigarettes) products will not be recruited for this study. Individuals with a 
history of keloid formation (who easily develop scars on their skin after an injury) are advised not to take part in this 
study. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  3  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Procedures of the study 
 
The study consists of four outpatient visits: an outpatient screening visit at the Clinical Center to determine eligibility, 
a baseline visit to study your metabolism before the intervention, a short outpatient visit to check how you are 
feeling, and a final visit 3 months after the baseline visit look for changes after the intervention.  Upon completing the 
final visit, you have the option to return 3 months later to come for another washout visit. This visit will look to see if 
the changes from the intervention continue to last even after stopping the study medication.  You will be given the study 
medication (colchicine) on the day you complete the baseline visit. 
 
Outpatient Screening Visit 
 
This visit will take about 3 hours to complete.  You will be seen on a weekday in the Clinical Center at the National 
Institutes of Health.  We ask that you remain fasting for 10 hours before coming to the clinic and have nothing to eat or 
drink except water that morning.  During this visit, we will perform the following: 
 
1. Protocol review and signing of consent form. We will go over the study in detail, and answer any questions. 
The consent form will need to be signed before you can take part in the study. 
 
2. Complete medical history and physical exam, with weight, height, and blood pressure measurement. 
 
3. An EKG will be performed to examine your heart function. 
 
4. Fasting blood tests to ensure that you are in good health. The analysis will examine blood cell count, liver and 
kidney function, cholesterol levels, blood sugar and insulin levels, thyroid tests, inflammation level, as well as 
reserve blood samples to be preserved for additional possible research tests.  We will also plan to do tests to find 
out if you have any differences in genes that may be important for metabolism and body weight. In addition to 
looking at some genes we already think are important for body weight, we will use new DNA sequencing 
technology that will look at all the human genes we know about. This is known as exome and genome 
sequencing. This new technology allows us to look at DNA in great detail. 
 
5. Urine sample collection to ensure that your kidneys work normally, that you are not taking any illicit drugs, 
and a pregnancy test (for women of childbearing age). 
 
6. Oral glucose tolerance test.  We will perform a test to study how your body handles sugar in the diet, called a 
2-hour glucose tolerance test.  You will drink a cup of sugar water and then will have your blood drawn over 2 
hours to look at your blood sugar levels. 
 
7. Dual energy x-ray absorptiometry (DEXA) to look at your body composition. The test involves lying still on a 
table while a small camera passes over your body. The dose of the x-ray is much less than the amount you would 
get from a normal chest x-ray. The total amount of time to do this test will be about 20-30 minutes. 
 
 
 
Baseline Visit 
 
If you qualify for participation in the study, you will be scheduled for the baseline visit.  We ask that you remain fasting 
for 10 hours before coming to the clinic and have nothing to eat or drink except water that morning.  You will be seen on 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  4  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
a weekday in the Clinical Center at the National Institutes of Health, and the visit will take about 8 hours to complete.  
During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement.  A 
questionnaire will also be performed. 
 
2. Fasting blood tests to look at your baseline metabolic and inflammatory levels, as well as reserve blood 
samples to be preserved for additional possible research tests including a sample for future genetic analysis.  We 
will insert a small needle into your vein (an intravenous line or I.V.) in order to obtain blood samples. 
 
3. Stool sample collection. We will obtain two stool samples to save for future experiments.  As part of this 
collection, we will ask you to keep track of your diet for 24 hours on a form that will be provided to you, as diet 
can affect the results of the stool testing.  You will also go over this “food record” in person with a nutritionist. 
 
4. Urine sample collection as described before. We will also collect urine over your eight hours of testing to save 
for future experiments. 
 
5. Frequently sampled intravenous glucose tolerance test (FSIVGTT).  This study tells us a lot about how 
sugar is used by your body, how well your insulin works, and how sensitive your body is to insulin.  The FSIVGTT 
study is done while you rest in bed.  A second IV line will be placed in your arm. We will give you some sugar 
water into one IV over a 2 minute period.  We will then draw blood samples from the other IV at -15, -10, -5, -1, 
2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 25, 30, 40, 50, 70, 100, 140, and 180 minutes (a total of 3 hours) to measure 
sugar and insulin levels.  Exactly 20 minutes into the test, we will give you a small amount of insulin through the 
IV.  A physician or nurse practitioner will be present during the first hour of the study. You can watch TV during 
this test. 
 
6. Computed Tomography (CT) Scan of the abdomen to look at where you tend to store your fat.  The test 
involves lying still on a movable table which passes through a large ring where the camera sits.  The test does 
involve radiation, but because we only need to take a snapshot of your abdomen, the method that will be used 
minimizes your exposure.  The total amount of time to do this test will be about 20-30 minutes. 
  
7. Subcutaneous Fat Biopsy. To examine the level of certain molecules in your fat tissue, a small sample of fat 
tissue will be taken from under the skin of your abdomen. Lidocaine, a local anesthetic, is used to numb the area.  
A needle will be used to remove a piece of fat tissue measuring about 1 ½ teaspoons.  A bandage is then applied 
to the site of needle insertion.  We can give you some mild pain medication such as Tylenol, or stronger 
medication if needed, after the biopsy. The biopsy will be taken from a place on your body that is normally 
covered and not easily seen.  
 
8. Dispense Study Medication. You will be given approximately an 8-week supply of colchicine to be taken two 
times a day (morning and late afternoon/evening) at home. Study medicine will be issued in a pill bottle with a 
“smart cap” that will record when you take your study medicine. The medication can be taken with or without 
food. We will give you a reminder alarm to help you remember when to take your medicine. If you forget to take 
a dose, then take it as soon as you remember.  But if it is within 4 hours of the time for your next dose, do not 
take a double dose.  Just skip the missed dose.  
 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  5  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Short Outpatient Visit 
 
To make sure that you doing well taking the medication, you will be seen on a weekday in the Clinical Center at the 
National Institutes of Health. This visit will take about 2 hours to complete.  We ask that you bring your bottle of pills 
with you. During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement. 
  
2. Fasting blood tests to ensure that you are in good health, to examine your inflammation levels, as well as 
reserve blood samples to be preserved for additional possible research tests. 
 
3. Urine sample collection as described before. 
 
4. Dispense Study Medication.  We will give you another bottle of colchicine and “smart cap” (about 8 weeks’ 
worth) to last you until the Final (3 month) Visit.  As before, if you forget to take a dose, then take it as soon as 
you remember.  But if it is within 4 hours of the time for your next dose, do not take a double dose.  Just skip the 
missed dose. 
 
Final Visit 
 
We will ask you to bring your bottle with any leftover pills to your final visit appointment.  We ask that you remain fasting 
for 10 hours before coming to the clinic and have nothing to eat or drink except water that morning.  You will be seen on 
a weekday in the Clinical Center at the National Institutes of Health, and the visit will take about 8 hours to complete.  
During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement.   
2. Fasting blood tests as described before. We will insert a small needle into your vein (an intravenous line or 
I.V.) in order to obtain blood samples. 
3. Stool sample collection as described before. 
4. Urine sample collection as described before. 
5. Frequently sampled intravenous glucose tolerance test (FSIVGTT) as described before.  
6. DEXA Scan as described before. 
7. CT Scan as described before. 
8. Subcutaneous Fat Biopsy as described before 
9. Exit questionnaire to tell us about your experience of participating in our protocol. 
 
Optional Washout Visit 
 
Because we would like to see if colchicine will continue to have lasting positive effects on your glucose regulation, 
metabolism, inflammation, and/or cardiovascular health even after you’ve stopped taking it, we invite patients to return to 
the NIH Clinical Center 3 months after finishing the study medication for repeat testing.   
 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  6  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
As before, we ask that you remain fasting for 10 hours before coming to the clinic and have nothing to eat or drink 
except water that morning.  You will be seen on a weekday in the Clinical Center at the National Institutes of Health, and 
the visit will take about 8 hours to complete.  During this visit we will perform the following:  
 
1. Interval medical history and physical exam, with weight, height, and blood pressure measurement.   
2. Fasting blood tests as described before. We will insert a small needle into your vein (an intravenous line or 
I.V.) in order to obtain blood samples. 
3. Stool sample collection as described before. 
4. Urine sample collection as described before.   
5. Frequently sampled intravenous glucose tolerance test (FSIVGTT) as described before.  
6. DEXA Scan as described before. 
7. CT Scan as described before. 
8. Subcutaneous Fat Biopsy as described before 
 
When the study is complete, you will return to the care of your regular physician. Participation in this study does not 
commit NIH to your long term care. 
 
Results of Tests at the NIH 
 
We will be measuring many things in your blood during your visits, and it is possible we might uncover a medical problem 
that requires treatment.  You will not be routinely provided treatment for any health condition discovered. However, you 
will be informed about such findings (e.g., high blood pressure) and any medically important information including blood 
tests or physical exam results will be forwarded to your primary care physician at your request.  Some of these medical 
problems might prevent you from participating further in the study. 
 
Risks and discomforts 
 
1. Physical examination. A physician or a nurse practitioner may need to examine you with your clothes off, with 
appropriate precautions to protect your privacy.  Some may find this examination embarrassing. 
 
2. Radiation Exposure: This research study involves exposure to radiation from three DEXA scans and three CT 
scans. Please note that this radiation exposure is not necessary for your medical care and is for research 
purposes only.   The NIH Radiation Safety Committee has reviewed the use of radiation in this research study and 
has approved this use as involving minimal risk and necessary to obtain the research information desired. 
 
Although each organ will receive a different dose, the amount of radiation exposure you will receive yearly from 
this study is equal to a uniform whole-body exposure of 0.093 rem. This calculated value is known as the 
“effective dose” and is used to relate the dose received by each organ to a single value. The amount of radiation 
you will receive in this study is below the dose guideline established by the NIH Radiation Safety Committee for 
research subjects.  This guideline is an effective dose of 5 rem received per year. 
 
For comparison, the average person in the United States receives a radiation exposure of 0.3 rem per year from 
natural background sources, such as from the sun, outer space, and from radioactive materials that are found 
naturally in the earth’s air and soil.  If you would like more information about radiation and examples of exposure 
levels form the other sources, please ask the investigator for a copy of the pamphlet called, An Introduction to 
Radiation for NIH Research Subjects. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  7  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
3. Blood withdrawal.  The blood withdrawal amount is well below the NIH guideline for a safe amount of blood 
withdrawal (550 cc every 8 weeks).  A small bruise may form at any site where the blood is taken.  The risk of 
infection or fainting is very small.  Inflammation or clotting of a vein also may rarely occur. 
 
Some of your blood will be sent to another laboratory within the NIH to examine your inflammation levels.  The 
samples will be coded, and only the investigators from this study will have access to the identity of the samples. 
 
4. Stool sample collection has no risk, and should only take a moment to complete.  The samples will be coded, 
and only the investigators from this study will have access to the identity of the samples. 
 
5. Urine sample collection has no risk and should only take a moment to complete.  If you do test positive for an 
illicit substance, the result will be part of your NIH Medical Record. 
 
6.  Questionnaires are not risky, but may be inconvenient because of the time necessary to complete them. 
 
7.  Oral glucose tolerance test.  This test is inconvenient because of the time it takes to complete.  The only risks 
from this kind of study are those described for any blood draw, as well as developing nausea from the oral 
glucose. Patients may transiently develop high blood sugar levels from the glucose, but it should normalize within 
a few hours and should not be clinically significant. 
 
8. Intravenous glucose tolerance test. This test is inconvenient because of the time it takes to complete.  You 
can watch TV during this test. The only risks from these kinds of studies are those described for any blood draw, 
the possibility of slight arm tenderness in the arm receiving the sugar infusion, (this tenderness goes away within 
a few minutes with gentle rubbing of the arm), and the possibility of a low blood sugar during the study.  With 
slightly low blood sugars (less than 50 mg/dL), participants may get hungry, have a headache, feel shaky or 
dizzy, may become drowsy, or may become sweaty.  With very low blood sugars (under 30 mg/dL) participants 
may have trouble speaking, be difficult to arouse, and even have seizures.  However, in the test we are doing, we 
will be giving you extra sugar to raise your blood sugar above normal, and then we will try to bring it back to 
normal (95-105 mg/dL) with insulin.  To do this, we will measure blood sugar at 2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 
24, 27, 30, 40, 50, 70, 90, 120, 140, 160, and 180 minutes (a total of 3 hours).  A physician or nurse practitioner 
will be present during the first hour of your test to make sure everything is working properly.  We expect that the 
chance of even a slightly low blood sugar is very low.  If a low blood sugar does not come up on its own quickly, 
the test will be stopped and you will be given sugar by vein to raise the blood sugar to normal. 
 
9. Fat tissue biopsies. Possible side effects of the biopsy procedure are pain during and for two to three days 
after the procedure, although rarely the biopsy site may be tender or sore or have bruising or swelling for 2-3 
weeks. Biopsy wounds usually heal with a very small, nearly unnoticeable scar, but sometimes a raised scar 
(keloid) or visible lump may result. Your risk is slightly higher if you are African American. Lidocaine injection for 
numbing before fat biopsies may cause some mild burning before the numbing takes effect. Rare adverse effects 
include infection at the biopsy sites or an allergic reaction to Lidocaine that may lead to a rash and/or swelling of 
the injected area. If you know you are allergic to Lidocaine, we will change to another local anesthetic. Another 
risk of the procedure is minor bleeding in the area of the biopsy. Some medications may increase the amount of 
bleeding from the biopsy. If you are taking medications such as Coumadin, Plavix or aspirin to thin your blood, 
you WILL NOT have a biopsy. If you are taking aspirin or non-steroidal medications such as Advil for pain you will 
need to stop taking these medicines for one week before the biopsy is performed. 
 
10. Smart cap has no risk and should work no differently than a regular pill bottle cap.  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  8  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
11. Medication.  The most common adverse effects from the medication used in this study are nausea, vomiting, 
diarrhea, and abdominal pain.  Some rare side effects (< 1%) have been reported including decreased production 
of red cells (which could make you feel tired), white blood cells (which can make more susceptible to infections), 
and/or platelets (which may make you more susceptible to bruising or bleeding), tingling (neuropathy), dizziness, 
muscle pain or weakness, rash, allergic reaction, decreased sperm count, and increased liver enzyme levels.  
These symptoms usually occur in people with underlying medical problems, or were on certain medications, that 
predisposed them to having the reaction.  In general, these symptoms resolved within a week once the 
medication was stopped. Although colchicine has been used for about 2000 years for gout, as with any 
medication, there is always the possibility of unpredicted side effects.  We will monitor you for all adverse effects.  
If (severe) adverse effects develop, we will decrease the dose, temporarily stop, or discontinue the medication.   
 
If you experience any of the following, contact our team right away: 
• 
Muscle weakness or pain 
• 
Numbness or tingling in the fingers or toes 
• 
Unusual bleeding or bruising 
• 
Severe diarrhea or vomiting 
 
There are no adequate well-controlled studies on the use of colchicine in pregnancy.  Data from a limited number 
of published studies found no evidence of an increased risk of miscarriage, stillbirth, or teratogenic effects among 
pregnant women using colchicine.  However, colchicine did demonstrate birth defects in the offspring of pregnant 
rats.  If you think you might become pregnant, we will ask that you not participate in this study. 
 
• 
Taking certain medicines with colchicine can cause your level of colchicine to be too high, especially if 
you have kidney or liver problems (refer to “Medication Guide” for more information).   
• 
Even medicines that you take for a short period of time, such as antibiotics, can interact with colchicine 
and cause serious side effects or death.  Please tell us about any new medicine you need to take so we 
can make sure you can continue using colchicine.  
• 
Avoid drinking grapefruit juice, as it can interfere with your body’s ability to breakdown colchicine. 
 
Keep the medication out of the reach of children. 
 
12. DNA testing. If you allow us to study your DNA, we will use it for genome sequencing. Genome sequencing is a 
test that could give us different kinds of results. These include: 
a. We could identify changes in genes that are related to metabolism and body weight. 
b. We could identify changes in genes that contribute to other diseases or problems.  
c. We could identify changes in genes that are not known to cause any disease. These are known as normal 
variations.  
d. We could find changes in genes that are new and of uncertain clinical importance. This means that we do not 
know if they could cause or contribute to a disease or if they are normal variations. 
 
Not all gene changes will have health implications for your family. Changes in genes that have health implications 
for your family: 
 
1. May have already caused health problems. 
2. May cause a health problem in the future. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  9  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
One of the goals of this study is to identify changes in genes that may be involved in obesity. This research may 
take years. If however we identify a genetic cause or likely cause of obesity, with your permission, we will contact 
you. Please let us know your preference by initialing one of these two statements: 
 
______  I would like to be contacted with information about the progress of this study and contacted 
about any results related to obesity. I understand that this research will take years and that a 
specific abnormality might not be identified in me. 
 
______ Please do not contact me regarding the progress of this study or any specific gene changes 
related to obesity. 
 
If we detect a genetic change that might be important for you, then we will have to confirm this result in a 
certified laboratory. For this confirmation, we will ask for a new sample of DNA from you. In most cases this will 
involve obtaining a small sample of blood (1-2 teaspoons). In some cases we can obtain enough DNA to confirm 
a genetic change by swabbing the inside of the cheek. You can decide whether you want to do that later, if we 
contact you with the information that we have found a possible important genetic difference. 
 
Identifying gene changes that are not related to the condition being studied is known as incidental medical 
information. 
 
We will find gene changes in everyone that we study, but we are only specifically looking for genes related to 
metabolism and body weight. We will not analyze your DNA for changes that are not related to metabolism and 
body weight. Even so, some gene changes not related to metabolism and body weight will be detected.  
 
We will only inform you only of changes that have urgent medical significance and would benefit from early 
medical treatment. An example of this would be a gene change that causes cancer and where you would benefit 
from early screening. We will not inform you of all gene changes that have uncertain health implications. For 
example we will not report gene changes that only predispose individuals to disease. An example of this would be 
a gene change that influences the risk of heart disease, but where the development of the disease is dependent 
on many genetic and non-genetic (such as diet and smoking) factors. If we find a change in a gene that is 
important to your family’s health, we will only be able to give you those results if the change has been confirmed 
in a certified laboratory. To make sure an error has not occurred, we would need to obtain a new sample of DNA 
from you to confirm the experimental results.  
 
In addition to knowing what we could find, we would like you to know the limitations of the genome sequencing 
and what we will NOT be able to tell you about the changes that we find.  
 
1. Not all gene changes that cause disease will be detected.  
2. Some changes that are not currently known to cause health problems will be found to cause health problems 
in the future. We cannot promise to be able to tell you about those changes in the future.  
3. We will not tell you about gene changes that are not known to have health implications, nor will we tell you 
about gene changes that have only reproductive consequences.  
4. This gene sequencing cannot be substituted for diagnostic testing recommended by another physician.  
 
Please initial all of the following statements to indicate that you understand the extent to which we will inform 
you about incidental genetic changes that we find:  
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  10  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
______ I understand that I will be informed only of genetic changes that researchers involved in this 
study feel are urgently important for my family’s health and that knowledge of these changes has 
the potential to provide a significant benefit for me or my family.  
 
______ I understand that investigators will not specifically look for gene changes not related to 
metabolism and body weight, and that identification of other disease-causing genes will only 
occur by chance depending on the analysis being done.  
 
______ I fully understand that even though they could have health or reproductive consequences, I will 
not be told about all genetic changes identified that are not related to metabolism and body 
weight.  
 
If we detect a gene change not related to metabolism and body weight and the investigators feel it meets the 
requirements of having urgent medical significance so that you would benefit from medical treatment, then you 
will be given a choice to learn or not learn about a genetic change that we find. You can chose not to be 
contacted at all if that is your preference. An exception to your ability to choose whether or not to find out about 
a gene change would be a gene change that investigators feel is of critical importance to your health. An example 
of this would be a gene change that has a high probability of causing cancer or a disease for which early 
treatment would be beneficial. Before confirming the result in a clinical laboratory we will contact you to obtain a 
new sample of DNA. 
 
If you have a gene change with urgent health implications, the NIH will confirm the genetic change present in 
one member of your family. We will discuss the results with you so that you understand who else in your family 
could be a carrier for this same change. We can help arrange for this testing to be done, but the NIH cannot 
promise to perform or pay for the clinical testing necessary to confirm or determine who else in your family may 
have this change in their DNA. 
 
Once a gene change is confirmed, we will discuss the results with you and make recommendations regarding 
appropriate medical follow up. The NIH cannot promise to perform or pay for recommended medical tests or 
evaluations. 
 
It is possible that a gene change will not be confirmed on subsequent testing. This could be due to an error in the 
DNA sequencing or an error in processing the DNA or cell lines. Although you likely will be glad that we did not 
confirm a problem, this may cause some anxiety and concern that you otherwise would not have experienced. 
 
Please let us know your preferences by initialing one of the following statements: 
 
______ I DO want to be re-contacted if genetic variants with urgent health implications are discovered 
during this research testing. 
 
______ I DO NOT want to be re-contacted if genetic variants with urgent health implications are 
discovered during this research testing. I understand that an exception to this choice, as 
described above, will be made for a gene change of critical medical significance. 
 
Emotional and psychological risks from DNA testing. Identification of gene changes could cause emotional 
and psychological problems. In some situations psychological counseling could be recommended. 
 
1. Learning about disease risk in your family can be distressing. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  11  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
2. Learning that you passed on a gene that does not work to your child can be distressing. 
3. Other members of your family could be upset to learn that they may be at risk for a disorder because of your 
participation in this study. 
 
You may be falsely reassured about your health status if we do not report any changes to you. 
 
Other risks of genetic testing. If we confirm a gene change in your DNA in a diagnostic laboratory, this 
information will become part of your medical record at the NIH. Some people are concerned that information 
about them from their medical records could be released. Possible problems include insurance or employment 
discrimination. Measures to protect the confidentiality of your information are described below. These problems 
may also occur if you disclose information yourself or agree to have your research records released. 
 
There are state and federal laws that protect against genetic discrimination. A federal law called the Genetic 
Information Nondiscrimination Act (GINA) generally makes it illegal for health insurance companies, group health 
plans, and most employers to discriminate against you based on your genetic information. According to this law, 
health insurance companies or group health plans (as of May 21, 2010) cannot request your genetic information 
or use it to make decisions about your eligibility or premiums; and employers cannot use it in deciding to hire, 
promote, or fire you or in setting the terms of your employment (as of Nov 21, 2009). 
 
Be aware that this Federal law does not protect you against genetic discrimination by companies that sell life 
insurance, disability insurance, or long-term care insurance. 
 
The following link contains details on this policy: 
http://www.genome.gov/Pages/PolicyEthics/GeneticDiscrimination/GINAInfoDoc.pdf 
 
You may ask your research team for additional information or a copy of The Genetic Information 
Nondiscrimination Act of 2008 informational document. 
 
Genetic studies can uncover unexpected family relationships. For example, it is possible that we might learn that 
a family member is not the biological child of the parents with whom she or he lives (for example, because of 
adoption). We will not ordinarily provide this type of information to any member of the family or to the referring 
physician. However, we may make exceptions under extraordinary circumstances if this information were required 
for the medical care of the individuals involved. If we are convinced this is necessary, we will provide the 
information to the physician providing medical care to the patient. 
 
Use of stored samples and data 
 
Future DNA Research. Currently we plan to sequence known genes. This represents only about 1% of your 
DNA sequence. In the future we may sequence other parts of your DNA, and eventually, we may completely 
sequence your DNA. These additional studies may occur years from now. Some of your DNA may be sent to other 
laboratories for specific tests. If this is done DNA will be coded and not have your name on the sample or the 
paperwork that goes to the laboratory. Should you withdraw from this study, we will keep your DNA for analysis 
unless you ask us to destroy the DNA samples. 
 
Please initial one of the following three statements regarding future research: 
 
______  DNA can be used for other kinds of future health-related research. This research is not limited to studies 
related to obesity, metabolism and body weight. This testing may be done by research laboratories that 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  12  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
are not at the NIH. I authorize use of these samples without my additional consent. I understand I will 
not be contacted if these samples are used in the future. 
 
______  I understand that genetic samples collected during these NIH visits will be saved and used for future 
experimental testing related to obesity, metabolism, and body weight. This testing may be done by 
research laboratories that are not at the NIH. I do NOT authorize use of these samples for any other 
purpose without my additional consent. I must be contacted and give consent if these samples are to be 
used in the future. 
______ Do not use my DNA for any future studies beyond those described above in this consent form. 
 
Future research with blood samples. Our specific research plans have been summarized in this consent form. 
In the course of the research, we will obtain blood samples. While we can do some of our tests immediately, we 
may want to store your blood samples in the freezer for future studies. In addition, certain information will be 
stored in your medical record. In the future, it is possible that your blood samples or medical records will be used 
for other research purposes that are not specifically outlined in this consent form. If this is done, samples will be 
coded, and you will not be identified by name. These samples may be stored at a separate site (called a 
repository) that specializes in storing clinical samples. You have the option, in the future, of requesting that these 
samples not be used for any additional testing. In addition, it is possible that some information obtained from 
these studies will be published in the medical literature. However, your identity will not be included in any 
publications. 
Please initial one of the following two statements: 
 
______ I understand that samples collected during these NIH visits will be saved and used for future 
experimental testing related to body weight, and/or metabolism. This testing may be done by research 
laboratories that are not at the NIH. I authorize other uses of these samples without my additional 
consent. I understand I will not be contacted if these samples are used in the future. 
 
______ I understand that samples collected during these NIH visits will be saved and used for future 
experimental testing related to body weight, and/or metabolism. This testing may be done by research 
laboratories that are not at the NIH. I do NOT authorize any other use of these samples without my 
additional consent. I must be contacted and give consent if these samples are to be used in the future. 
 
All through the process of the study and afterwards, the confidentiality of participants will be protected by using 
codes and medical record numbers in recording your information and test results. Only medical personnel 
involved in this study will have access to participants’ names, test results, and patient code numbers. 
 
You need to be aware that DNA sequence is like a fingerprint. Theoretically if enough DNA sequence information 
is available, someone could identify you based on his/her DNA sequence. To facilitate genetic research, your DNA 
sequence information may be deposited in other databases. In this case, unless we have your permission, we will 
deposit the data in a manner that would not allow someone to identify you. Please understand that this 
information cannot be removed once it is deposited. 
 
Please initial one of the following boxes. 
 
______ I do not want DNA sequence data to be deposited in any database other than the one associated with 
this study. 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  13  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
______ My DNA sequence data can be deposited in databases that limit access to IRB (ethics board) approved- 
researchers. 
 
______ My DNA sequence can be deposited in a database that is available only to scientists but that does not 
require IRB approval of research studies. I understand that someone could theoretically identify me from 
this information. 
 
Potential benefits of participation 
 
We are hopeful that your participation in this study will provide evidence as to whether colchicine will help metabolic 
parameters in obese individuals.  However, you might not benefit directly from participating in this study.  Should we find 
abnormalities in any of your test results, you will be notified and receive a copy to assist you in seeking further medical 
evaluation. This information may or may not improve your health.  
 
Right of Withdrawal and Conditions for Early Withdrawal  
 
You may withdraw from the study at any time and for any reason without loss of benefits or privileges to which you are 
otherwise entitled.  
 
Discussion of New Findings with You 
 
After all participants have completed the study, we will inform you about which medicine you took and, once the study is 
fully analyzed, let you know if colchicine seemed to help with inflammation and insulin resistance. There is no general 
plan to share your individual test results with you. However, if any findings suggest you have a medical issue, we will 
provide this information to you and your primary care provider. You may request a copy of your routine laboratory tests if 
you desire.  
 
Study Termination 
 
You may be asked to end your participation in this study at any time if we believe that continuation is not in your best 
medical interest or if you are unable to comply with the requirements of the study.  
 
Alternatives to Participation 
 
The alternative to this study is not to participate. You may be eligible for other studies in the NIH. You may learn more 
about them through www.clinicaltrials.gov. 
 
Compensation 
You will be compensated for the time and inconvenience associated with participation according to NIH research 
volunteer guidelines.  Compensation for completing all of the testing described above is $100 for the outpatient screening 
visit, $50 for the safety visit, and $300 each for the baseline, final, and washout visits.  The total amount you could 
receive for participation if you complete all parts of this study is $1050. 
 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  14  of  15  pages 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Conflict of Interest 
 
The NIH and members of this research team have no financial interest related to this research study.  
 
Posting of Research Results on www.ClinicalTrials.gov  
 
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This web site 
will not include information that can identify you. At most the Web site will include a summary of the results. You can 
search this Web site at any time. 
 
 
______  I have received a copy of the signed consent form. 
 


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  15  of  15  pages 
 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
OTHER PERTINENT INFORMATION 
 
1. Confidentiality.  When results of an NIH research study are reported in medical journals or at scientific meetings, the 
people who take part are not named and identified.  In most cases, the NIH will not release any information about your 
research involvement without your written permission.  However, if you sign a release of information form, for example, 
for an insurance company, the NIH will give the insurance company information from your medical record.  This information 
might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance. 
 
The Federal Privacy Act protects the confidentiality of your NIH medical records.  However, you should know that the Act 
allows release of some information from your medical record without your permission, for example, if it is required by the 
Food and Drug Administration (FDA), members of Congress, law enforcement officials, or authorized hospital accreditation 
organizations. 
 
2. Policy Regarding Research-Related Injuries.  The Clinical Center will provide short-term medical care for any 
injury resulting from your participation in research here.  In general, no long-term medical care or financial compensation 
for research-related injuries will be provided by the National Institutes of Health, the Clinical Center, or the Federal 
Government.  However, you have the right to pursue legal remedy if you believe that your injury justifies such action. 
 
3. Payments.  The amount of payment to research volunteers is guided by the National Institutes of Health policies.  In 
general, patients are not paid for taking part in research studies at the National Institutes of Health.  Reimbursement of 
travel and subsistence will be offered consistent with NIH guidelines. 
 
4. Problems or Questions.  If you have any problems or questions about this study, or about your rights as a 
research participant, or about any research-related injury, contact the Principal Investigator, Jack A. Yanovski, MD, PhD; 
Building 10-CRC Room 1-3330, Telephone: 301-496-4686 or Associate Investigator Andrew Demidowich, MD; Building 10-
CRC Room 1-3330, Telephone: 301-496-4686. 
 
You may also call the Clinical Center Patient Representative at 301-496-2626. 
 
5. Consent Document.  Please keep a copy of this document in case you want to read it again. 
 
COMPLETE APPROPRIATE ITEM(S) BELOW: 
 
A. Adult Patient’s Consent 
B. Parent’s Permission for Minor Patient. 
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby consent to take 
part in this study. 
I have read the explanation about this study and have been given the 
opportunity to discuss it and to ask questions.  I hereby give permission 
for my child to take part in this study.   
(Attach NIH 2514-2, Minor’s Assent, if applicable.) 
 
  
 
 
  
 
Signature of Adult Patient/Legal Representative 
Date 
 
 
 
Print Name 
Signature of Parent(s)/Guardian 
Date 
 
 
 
Print Name 
C. Child’s Verbal Assent (If Applicable) 
The information in the above consent was described to my child and my child agrees to participate in the study. 
 
 
 
  
 
 
 
 
Signature of Parent(s)/Guardian 
Date 
 
Print Name 
THIS CONSENT DOCUMENT HAS BEEN APPROVED FOR USE  
FROM JANUARY 24, 2018 THROUGH FEBRUARY 24, 2019. 
 
 
  
 
 
  
 
Signature of Investigator 
Date 
 
 
 
Print Name 
Signature of Witness 
Date 
 
 
 
Print Name 
 


 
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
               • Adult Patient or     •  Parent, for Minor Patient 
 
 
INSTITUTE: 
Instituto Nacional de Salud Infantil y Desarrollo Humano (National Institute of Child Health and  
 
Human Development) 
 
 
STUDY NUMBER: 
14-CH-0119 
PRINCIPAL INVESTIGATOR:  Jack Yanovski, M.D. 
 
 
STUDY TITLE: 
Estudio preliminario de los efectos de la colchicina en adultos no diabéticos con síndrome 
metabólico 
  
(Pilot Study of the Effects of Colchicine in Non-Diabetic Adults with Metabolic Syndrome) 
 
 
Continuing Review Approved by the IRB on 01/24/18 
Amendment Approved by the IRB on 07/13/18 (S)  
 
 
Date Posted to Web: 08/07/18 
Open-Label Arm Spanish 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY 
 
•   Adult Patient or    •   Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent (6) 
 
 
INTRODUCCIÓN 
 
Deseamos invitarle a participar en un estudio de investigación en los Institutos Nacionales de Salud (National Institutes of 
Health, NIH). 
 
En primer lugar, queremos que Ud. sepa que: 
La participación en una investigación del NIH es totalmente voluntaria. 
Usted puede decidir no participar o retirarse del estudio en cualquier momento. En cualquier caso, no perderá 
ninguna compensación a la que pueda tener derecho. No obstante, para recibir atención médica en el NIH usted 
debe participar en un estudio o estar en evaluación para participar en uno. 
 
Es posible que no reciba ningún beneficio por su participación. Con la investigación podemos adquirir 
conocimientos que ayuden a otras personas en el futuro. 
 
En segundo lugar, algunas personas pueden tener creencias personales, religiosas o éticas que limiten los tipos de 
tratamientos médicos o de investigación que deseen recibir (por ejemplo, transfusiones de sangre). Si usted es una de 
esas personas, hable al respecto con sus médicos o con el equipo de investigación del NIH antes de acceder a participar 
en el estudio. 
 
El estudio se describe en las siguientes páginas. Antes de decidir participar, tómese todo el tiempo que necesite para 
hacer preguntas y hablar del estudio con cualquier persona del NIH, o con su familia, amigos, médico personal o 
cualquier otro profesional de la salud.
 
Propósito de este Estudio 
Aproximadamente 30% de los adultos en los EE.UU. tienen un índice de masa corporal (IMC ) superior a 30 (kg /m2), y 
están en mayor riesgo de una serie de problemas médicos, incluyendo la presión arterial alta, colesterol alto en la sangre, 
niveles altos de triglicéridos, azúcar en la sangre (diabetes) y enfermedades del corazón. Se cree que tener sobrepeso, 
puede llevar a un estado de inflamación aunque de nivel bajo, y que esta inflamación puede conducir a algunos de los 
problemas médicos asociados con la obesidad. El propósito de este estudio es investigar si un medicamento llamado 
colchicine puede mejorar el metabolismo de los adultos que tienen complicaciones médicas debido a su sobrepeso 
corporal (estas complicaciones son algunas veces llamadas, "síndrome metabólico"), y han desarrollado altos niveles de 
azúcar en la sangre (diabetes). 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  2  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
Colchicine es una medicación anti- inflamatoria que se ha utilizado durante siglos en el tratamiento de la gota. A partir de 
estudios en animales y estudios en humanos, existe alguna evidencia de que los medicamentos anti-inflamatorios 
como colchicine pueden mejorar la capacidad del páncreas para secretar insulina y la capacidad del cuerpo para regular el 
azúcar. Les pedimos que se unan a nuestro estudio, por el cual esperamos averiguar si colchicine puede mejorar la 
regulación del azúcar y los parámetros metabólicos. 
  
Si califica y está de acuerdo en participar, Ud. será una de siete personas asignadas al azar para tomar tabletas de 
colchicine por vía oral, dos veces al día durante 3 meses. Las tabletas de colchicine vendrán en la misma dosis que está 
disponible en las farmacias y se prescribe para una enfermedad llamada "gota": 0.6 miligramos. 
  
Cuando se haya completado el estudio, le enviaremos cada uno de los participantes información sobre los resultados y les 
daremos a conocer si la medicación se ayudan. 
   
Los participantes del estudio tendrán que venir al Centro Clínico del NIH para cuatro consultas ambulatorias, con una 
quinta consulta ambulatoria opcional. Es importante que los participantes llegen en ayunas (sin alimentos ni bebidas 
aparte de agua) a cada una de estas visitas. Los participantes serán compensados por su tiempo y cualquier 
inconveniente (ver más abajo: Compensación en la página 5). 
 
Población de estudio 
Deseamos reclutar a siete adultos con sobrepeso y diabetes, controlada exclusivamente con dieta. 
  
Quién puede participar en este estudio 
Usted puede ser elegible para este estudio de investigación si es mayor de 18 años de edad; si tiene un índice de masa 
corporal mínimo de 30, el cual se calcula dividiendo el peso del individuo en kilogramos, por su altura en metros, al 
cuadrado, (Kg/m2); pesar menos de 450 libras, y que se encuentre en buen estado de salud general. Usted también tiene 
que cumplir con ciertos niveles de resistencia a la insulina y a la inflamación, medidas por pruebas de laboratorio, y tener 
diabetes tipo 2 controlada con dieta para participar en todo el estudio. Si usted es una mujer en edad de procrear, se le 
pedirá que use un método efectivo de control de la natalidad antes de participar en este studio. 
 
Quienes no pueden participar en este estudio 
Usted no puede ser elegible para este estudio si tiene una enfermedad médica grave que pudiera interferir con las 
pruebas o mediciones del estudio, como enfermedades del corazón, riñón, hígado, pulmón, sangre, intestinal o 
enfermedades endocrinas o presión arterial alta no controlada. Si usted está usando un medicamento que afecta 
el metabolismo del azúcar y la grasa o la absorción en su cuerpo, o un medicamento que no se debe tomar con  
colchicine, es posible que no sea elegible para participar. Tampoco son elegibles las mujeres que están embarazadas o 
lactando, o tienen intención de quedar embarazadas; las personas que han tenido un cambio de peso reciente superior al 
3% del peso corporal total, han estado utilizando medicamentos para reducir el peso, han usado recientemente la 
colchicina, tener una alergia conocida a la colchicina, o utilizan productos de tabaco o nicotina (p. ej. e-cigarrillos), no 
serán reclutadas para este estudio. Se recomienda a las personas con antecedentes de formación de queloides (que  
fácilmente desarrollan cicatrices en su piel después de una lesión) no participar en este estudio. 
  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  3  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
Procedimientos del estudio 
  
El estudio consta de cuatro visitas ambulatorias en el Centro Clínico: una visita para determinar elegibilidad, una 
visita inicial para estudiar su metabolismo antes de la participación, una corta visita ambulatoria para comprobar 
cómo se siente el participante durante el estudio, y una visita final 3 meses después de la visita inicial para ver los 
cambios después de la participación. Al término de la visita final, usted tiene la opción de volver 3 meses después para 
otra visita en la cual se quiere ver si los cambios observados mientras la participacion en el estudiopermanecen incluso 
después de suspender la medicación del estudio. Se le dará la medicación del estudio (colchicina) en el día de completar 
la Visita Inicial. 
 
Visita Ambulatoria de Selección de Pacientes  
  
Esta visita tomará unas 3 horas para realizarse. Usted será visto en un día de semana en el Centro Clínico del NIH. Le 
pedimos permanecer en ayunas durante las 10 horas anteriores a su llegada a la clínica y no debe comer o beber nada, 
excepto agua por la mañana. Durante esta visita, vamos a realizar lo siguiente: 
  
1. Protocolo y firma del formulario de consentimiento. Vamos a repasar el estudio en detalle y a responder 
cualquier pregunta. El formulario de consentimiento debe ser firmado antes de poder tomar parte en el estudio. 
 
2. Historia médica completa y un examen físico, con el peso, la altura, y la medición de la presión arterial. 
 
3. Un ECG se realizará para examinar la función de su corazón. 
 
4. Los análisis de sangre en ayunas para asegurarse de que usted se encuentra en buen estado de salud. El 
análisis examinará el recuento de células de la sangre, función hepática y renal, niveles de colesterol, los niveles 
de azúcar e insulina en sangre, pruebas de función tiroidea, nivel de la inflamación, así como muestras de sangre 
de reserva para ser preservadas para poder examinar durante futuras investigaciónes. También realizaremos 
pruebas para determinar si usted tiene alguna diferencia en genes que pueden ser importantes para el 
metabolismo y el peso corporal. Además para buscar algunos genes que ya nosotros pensamos que son 
importantes para el peso corporal, vamos a utilizar nueva tecnología de secuenciación de DNA que se verá en 
todos los genes humanos que conocemos. Esto se conoce como “exome” y secuenciación del genoma. Esta 
nueva tecnología nos permite mirar el ADN en gran detalle. 
 
5. Recogida de muestras de orina para asegurarse de que sus riñones funcionan normalmente, que no está 
tomando cualquier droga ilícita, y una prueba de embarazo (para las mujeres en edad fértil). 
 
6. Prueba de tolerancia a la glucosa oral. Vamos a realizar una prueba para examinar si usted tiene diabetes, la 
llamamos prueba de tolerancia a la glucosa de 2 horas. Va a tomar una taza de agua con azúcar y luego se 
tomarán muestras 1 y 2 horas después para mirar su nivel de azúcar en la sangre. 
 
7. Absorciometría dual de rayos X (DEXA) para examinar su composición corporal. La prueba consiste en 
permanecer inmóvil sobre una mesa mientras una pequeña cámara pasa sobre su cuerpo. La dosis de los rayos X 
es mucho menor que la cantidad que se obtiene de una radiografía de pecho normal. La cantidad total de tiempo 
para realizar esta prueba será de unos 20 a 30 minutos. 
 


 
  
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Visita Inicial 
  
Si reúne los requisitos para participar en el estudio, se le cita para la visita inicial. Le pediremos que permanezca en 
ayunas durante 10 horas antes de llegar a la clínica y no comer o beber nada, excepto agua por la mañana. Usted será 
visto en un dia entre semana en el Centro Clínico de los Institutos Nacionales de Salud, y la visita tomará alrededor de 8 
horas para completarse. Durante esta visita vamos a realizar lo siguiente:  
1. Intervalo de historia clínica y examen físico, con el peso, la altura, y la medición de la presión arterial. También 
se completará un cuestionario. 
 
2. Los análisis de sangre en ayunas para mirar su metabolismo basal y los niveles inflamatorios, así como 
muestras de sangre de reserva para ser preservados para las pruebas de investigación adicionales posibles, 
incluyendo una muestra para futuro análisis genético. Vamos a insertar una pequeña aguja en la vena (una vía 
intravenosa o IV) con el fin de obtener las muestras de sangre. 
 
3. Obtención de muestras de heces, obtendremos dos muestras de heces para conservar para futuros 
experimentos. Como parte de esta colección, le pediremos que mantenga un record de su dieta por 24 horas en 
un formulario que se le entregara a usted, y asi ver como la dieta puede afectar los resultados de las pruebas de 
heces. Los resultados de este “diario de nutricion” irá con un nutricionista. 
 
4. Obtención de muestras de orina como se describe antes. También vamos a recoger la orina durante su visita a 
ahorrar para futuros experimentos. 
 
5. Prueba de tolerancia a la glucosa intravenosa muestreado frecuentes.  Este estudio nos dice mucho 
acerca de cómo su cuerpo utiliza el azúcar, qué tan bien está funcionando su insulina y cómo es la sensibilidad de 
su cuerpo a la insulina. El estudio FSIVGTT se hace mientras usted descansa en una cama. Una segunda línea IV 
se coloca en su brazo. Le daremos un poco de agua de azúcar en una vía intravenosa durante un período de 2 
minutos. Entonces vamos a tomar muestras de sangre de la otra IV en -15, -10, -5, -1, 2, 3, 4, 5, 6, 8, 10, 14, 
19, 22, 25, 30, 40, 50, 70, 100, 140, y 180 minutos (un total de 3 horas ) para medir los niveles de azúcar e 
insulina . Exactamente a los 20 minutos en la prueba, le daremos una pequeña cantidad de insulina a través de la 
IV. Un médico o enfermera practicante estará presente durante la primera hora del estudio. Usted puede ver la 
televisión durante esta prueba. 
 
6. Tomografía Computarizada (TC) del abdomen para observar donde se tiende a almacenar su grasa. La 
prueba consiste en permanecer quieto en una mesa móvil que pasa por un gran anillo donde esta ubicada la 
cámara. La prueba implica radiación, pero solo porque tomaremos una foto de su abdomen, el método que se 
utilizará minimiza su exposición. La cantidad total de tiempo para realizar esta prueba será de unos 20 a 30 
minutos 
 
7. Subcutánea Biopsia de grasa. Para examinar el nivel de ciertas moléculas en el tejido graso, se tomará una 
pequeña muestra de tejido graso de debajo de la piel de su abdomen. Para adormecer el área donde se tomarà 
la muestra, se utilizará la lidocaína, un anestésico local. Una aguja se utilizará para extraer una porción de tejido 
graso que mide alrededor de 1 ½ cucharaditas. Un vendaje se aplica entonces al sitio de inserción de la aguja. 
Podemos darle algún medicamento para el leve dolor, como Tylenol o medicamento más fuerte si es necesario, 
después de la biopsia. La biopsia se tomará de un lugar del cuerpo que normalmente está cubierto y que no se 


 
  
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ve fácilmente. 
8. Los medicamentos de dispensación de Estudio. Se le dará un suministro de aproximadamente 8 semanas 
de la medicación del estudio para ser tomado dos veces al día (mañana y tarde/noche) en casa. El medicamento 
del estudio estará en un frasco de tabletas con una "tapa inteligente" que registrará cuando se toma el 
medicamento de estudio. El medicamento se puede tomar con o sin alimentos. Le daremos una alarma de 
recordatorio para ayudarle a recordar cuándo tomar su medicamento. Si se olvida de tomar una dosis, tómela tan 
pronto como lo recuerde. Pero si está dentro de las 4 horas de la hora de su siguiente dosis, no tome una dosis 
doble. Sólo tome la dosis olvidada. 
 
Visita Ambulatoria Corta 
  
Para asegurarse de que está tomando bien el medicamento, usted será visto en un día de la semana en el Centro Clínico 
de los Institutos Nacionales de Salud. Esta visita se tomara alrededor de 2 horas en completarse. Le pedimos que traiga 
su botella de píldoras con usted. Durante esta visita vamos a realizar lo siguiente:  
 
1. Intervalo de historia clínica y examen físico, con el peso, la altura, y la medición de la presión arterial. 
 
2. Análisis de sangre en ayunas, para asegurarse de que está en buen estado de salud, para examinar sus niveles 
de inflamación, así como muestras de sangre de reserva para ser preservado para las pruebas adicionales 
futuras.  
 
3. Recogida de muestras de orina como se describe antes. 
 
4. Los medicamentos de dispensación de Estudio. Le daremos otra botella de la medicación del estudio con 
"tapa inteligente" (para un periodo de cerca de 8 semanas) para que le dure hasta la visita final (3 meses). Al 
igual que antes, si olvida tomar una dosis, tómela tan pronto como lo recuerde. Pero si está dentro de las 4 horas 
de la hora de su siguiente dosis, no tome una dosis doble. Omita la dosis olvidada. 
  
Visita Final 
  
Le pediremos traer su botella con pastillas sobrantes de su anterior visita. Le pedimos permanecer en ayunas durante 10 
horas antes de llegar a la clínica y no comer o beber nada excepto agua por la mañana. Usted será visto en un día entre 
semana en el Centro Clínico de los Institutos Nacionales de Salud, y la visita se llevará alrededor de 8 horas para 
completar. Durante esta visita vamos a realizar lo siguiente:  
 
1. Intervalo historia clínica y examen físico, con el peso, la altura, y la medición de la presión arterial  
2. Análisis de sangre en ayuno como se describe anteriormente. Vamos a insertar una pequeña aguja en la vena 
(una vía intravenosa o IV) con el fin de obtener muestras de sangre. 
3. Recogida de muestras de heces como se describe antes.  
4. Recogida de muestras de orina tal como se describe antes. 
5. Prueba muestreado frecuentes tolerancia a la glucosa intravenosa (FSIVGTT) como se describe antes. 
6. DEXA Scan como se describe antes. 
7. CT Scan como se describe antes 
8. Grasa subcutánea biopsia como se ha descrito antes 
9. Cuestionario final para contarnos acerca de su experiencia de participar en nuestro protocolo. 


 
  
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Visita Opcional 
  
Debido a que nos gustaría ver si la colchicina seguirá teniendo efectos positivos duraderos en la regulación del 
metabolismo de su glucosa, la inflamación, y/o su salud cardiovascular, incluso después de haber dejado de tomarlo, 
invitamos a los pacientes a volver al Centro Clínico de los NIH 3 meses después de terminar la medicación del estudio 
para repetir las mismas pruebas. 
  
Al igual que antes, le pedimos que permanecer en ayunas durante 10 horas antes de llegar a la clínica y no comer o 
beber nada, excepto agua por la mañana. Usted será visto en un día entre semana en el Centro Clínico de los Institutos 
Nacionales de Salud, y la visita llevará alrededor de 8 horas para completarse. Durante esta visita vamos a realizar lo 
siguiente: 
 
1. Intervalo historia clínica y examen físico, con el peso, la altura, y la medición de la presión arterial   
2. Análisis de sangre el ayuno como se describe anteriormente. Vamos a insertar una pequeña aguja en la vena 
(una vía intravenosa o IV) con el fin de obtener muestras de sangre. 
3. Recogida de muestras de heces como se describe antes.  
4. Recogida de muestras de orina tal como se describe antes. 
5. Prueba muestreado frecuente de tolerancia a la glucosa intravenosa (FSIVGTT) como se describe 
antes. 
6. DEXA Scan como se describe antes. 
7. CT Scan como se describe antes. 
8. Grasa subcutánea biopsia como se ha descrito antes 
  
Cuando el estudio se haya completado, volverá al cuidado de su médico de cabecera. La participación en este estudio no 
compromete al NIH a su cuidado a largo plazo. 
  
Los resultados de pruebas realizadas en el NIH 
  
Estaremos midiendo muchas cosas en su sangre durante sus visitas, y podríamos descubrir algún problema médico que 
requiere tratamiento. Ud. no recibirá de forma rutinaria tratamiento para cualquier condición de salud descubierto. Sin 
embargo, se le informará sobre estos hallazgos (por ejemplo: presión arterial alta) y cualquier información de importancia 
médica que resulten de análisis de sangre o del examen físico, serán remitidos a su médico de atención primaria en su 
solicitud. Algunos de estos problemas médicos podrían impedir su participación más en el estudio. 
 
Riesgos y molestias 
  
1. El examen físico. Un médico o una enfermera puede tener que le examinar pidiéndole que se quite su ropa, 
con las precauciones adecuadas para proteger su privacidad. Algunos pueden encontrar este examen vergonzoso. 
 
2. Exposición a la radiación: Este estudio de investigación implica la exposición a la radiación de tres imagenes 
DEXA y tres tomografías computarizadas. Tenga en cuenta que esta exposición a la radiación no es necesario 
para su atención médica y es sólo para fines de investigación. El Comité de Seguridad Radiológica NIH ha 
revisado el uso de la radiación en este estudio de investigación y ha aprobado este uso ya que implica un riesgo 
mínimo y necesario para obtener la información de investigación deseada.  


 
  
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Aunque cada órgano recibirá una dosis diferente, la cantidad de exposición a la radiación que recibirá anualmente 
de este estudio es igual a una exposición uniforme de todo el cuerpo a 0.093 rem. Este valor calculado se conoce 
como la "dosis efectiva" y se utiliza para relacionar la dosis recibida por cada órgano a un solo valor. La cantidad 
de radiación que recibirá en este estudio es inferior a la pauta de dosis establecido por el Comité de Seguridad 
Radiológica NIH para los sujetos de investigación. Esta pauta establece una dosis efectiva de 5 rem recibido por 
año. 
 
Por comparación, la persona promedio en los Estados Unidos recibe una exposición a la radiación de 0,3 rem por 
año a partir de fuentes naturales, como el sol, el espacio exterior, y de materiales radiactivos que se encuentran 
naturalmente en el aire y el suelo. Si desea más información sobre la radiación y los ejemplos de los niveles y 
forma de exposicion a otras fuentes, por favor pregunte al investigador para obtener una copia del folleto 
titulado, An Introduction to Radiation for NIH Research Subjects. 
 
3. La extracción de sangre. La cantidad de extracción de sangre es muy por debajo de la directriz del NIH para 
una cantidad segura de extracción de sangre (550 cc cada 8 semanas). Un pequeño moretón se puede formar en  
 
cualquier sitio donde se toma la sangre. El riesgo de infección o desmayo es muy pequeña. La inflamación o 
coagulación de una vena también pueden ocurrir raramente. 
 
Una parte de su sangre será enviado a otro laboratorio dentro del NIH para examinar sus niveles de inflamación. 
Las muestras serán codificadas, y sólo los investigadores de este estudio tendrán acceso a la identidad de las 
muestras 
 
4. Recogida de muestras de heces no tiene ningún riesgo, y sólo debe tomar un momento para recogerlas. Las 
muestras serán codificadas, y sólo los investigadores de este estudio tendrán acceso a la identidad de las 
muestras. 
 
5. La recogida de muestras de orina no tiene ningún riesgo y sólo toma un momento para completar. Si el 
resultado es positivo para una sustancia ilícita, el resultado será parte de su expediente médico NIH. 
 
6. Los cuestionarios no son peligrosos, pero pueden ser un inconveniente debido al tiempo necesario para su 
realización.  
 
7. Prueba oral de tolerancia a la glucosa. Esta prueba es un inconveniente debido al tiempo que se tarda en 
completar. Los únicos riesgos de este tipo de estudio son las descritos para cualquier extracción de sangre, así 
como el desarrollo de las náuseas por la glucosa oral. Algunos pacientes pueden desarrollar de forma transitoria 
niveles altos de azúcar en la sangre a partir de la glucosa, pero deben normalizarse a las pocas horas y no deben 
ser clínicamente significativos. 
 
8. Prueba de tolerancia a la glucosa intravenosa. Esta prueba es un inconveniente debido al tiempo que se 
tarda en completar. Usted puede ver la televisión durante esta prueba. Los únicos riesgos de este tipo de 
estudios son las descritas para cualquier extracción de sangre, la posibilidad de una ligera sensitividad en el brazo 
al recibir la infusión de azúcar, (esa sensitividad desaparece al cabo de unos minutos con el roce suave del 
brazo), y la posibilidad de un bajo nivel de azúcar en la sangre durante el estudio. Cuando la azúcar en sangre 
esta baja (menos de 50 mg/dl), los participantes pueden tener hambre, tener dolor de cabeza, sentirse 


 
  
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temblorosos o mareados o pueden llegar a ponerse sudorosos. Con azúcar en la sangre muy bajos (menos de 30 
mg /dl) participantes pueden tener problemas para hablar, dificultad para despertar, e incluso tener convulsiones.  
 
Sin embargo, en la prueba que estamos haciendo, le estaremos dando azúcar extra para elevar el azúcar en la 
sangre por encima de lo normal, y luego vamos a tratar de traerlo de vuelta a la normalidad (95-105 mg / dL) 
con insulina. Para ello, vamos a medir el azúcar en la sangre a los 2, 3, 4, 5, 6, 8, 10, 14, 19, 22, 24, 27, 30, 40, 
50, 70, 90, 120, 140, 160, y 180 minutos (un total de 3 horas). Un médico o enfermera practicante estará 
presente durante la primera hora de su prueba para asegurarse de que todo funciona correctamente. Esperamos 
que la posibilidad de un nivel de azúcar en sangre bajo sea muy pequeña. Si un bajo nivel de azúcar en la sangre 
no sube por sí sola con rapidez, se detendrá la prueba y se le dará el azúcar por vía IV para elevar el azúcar en la 
sangre a la normalidad 
 
9. Biopsias de grasa. Los posibles efectos secundarios de la biopsia son el dolor durante y durante dos o tres días 
después del procedimiento. Aunque rara vez, la zona de la biopsia puede estar sensible o adolorida o tener 
moretones o hinchazón durante 2-3 semanas. Heridas biopsia suelen sanar con una cicatriz muy pequeña, casi 
imperceptible, pero a veces una cicatriz elevada (queloides) o bulto visible puede resultar. Su riesgo es 
ligeramente mayor si usted es afroamericano. Inyección de lidocaína para adormecer antes de biopsias de grasa 
puede causar un poco de ardor suave antes de que llegue el entumecimiento. Efectos adversos raros incluyen la 
infección en los sitios de biopsia o una reacción alérgica a la lidocaína que puede llevar a una erupción y/o 
hinchazón de la zona de inyección. Si usted sabe que es alérgico a la lidocaína, cambiaremos a otro anestésico 
local. Otro de los riesgos del procedimiento es sangrado menor en el área de la biopsia. Algunos medicamentos  
 
pueden aumentar la cantidad de sangrado de la biopsia. Si está tomando medicamentos como Coumadin, Plavix 
o aspirina para adelgazar la sangre, usted no tendrá una biopsia. Si está tomando aspirina o medicamentos no 
esteroides como Advil para el dolor tendrá que dejar de tomar estos medicamentos durante una semanaantes de 
realizar la biopsia. 
 
10. Tapa inteligente no tiene riesgo, y debería funcionar igual que una tapa de botella regular. 
  
11. Medicamentos. Los efectos adversos más comunes de los medicamentos utilizados en este estudio son: 
náuseas, vómitos, diarrea y dolor abdominal. Se han observado algunos efectos secundarios raros (<1%) son los 
siguientes: disminución de la producción de glóbulos rojos (que podría hacer que se sienta cansado), glóbulos 
blancos (que puede hacer más susceptibles a las infecciones), y/o plaquetas (que pueden hacerle más 
susceptibles a la aparición de moretones o sangrado), hormigueo (neuropatía), mareo, dolor muscular o 
debilidad, erupción, reacción alérgica, disminución del recuento de espermatozoides , y aumento de los niveles de 
enzimas hepáticas. Estos síntomas generalmente ocurren en personas con problemas médicos subyacentes, o 
estaban en ciertos medicamentos, que les predispone a tener la reacción. En general, estos síntomas se 
resolvieron dentro de una semana una vez que se suspende el medicamento. Aunque la colchicine se ha utilizado 
durante unos 2000 años para la gota, al igual que con cualquier medicamento, siempre existe la posibilidad de 
efectos secundarios imprevistos. Le supervisaremos por todos los efectos adversos. Si se desarrollan (severos) 
efectos adversos, vamos a disminuir la dosis, interrumpir temporalmente o suspender la medicación. 
  
Si usted experimenta cualquiera de los siguientes efectos, póngase en contacto con nuestro equipo de inmediato: 
• 
Debilidad muscular o dolor 
• 
El entumecimiento u hormigueo en los dedos o dedos de los pies 


 
  
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• 
Sangrado o moretones inusuales 
• 
La diarrea grave o vómitos 
 
No hay estudios bien controlados adecuados sobre el uso de colchicine durante el embarazo. Los datos de un 
número limitado de estudios publicados no encontraron evidencia de un mayor riesgo de aborto involuntario, 
muerte, o efectos teratogénicos en las mujeres embarazadas que usan colchicina. Sin embargo, la colchicine 
mostró defectos de nacimiento en las crías de ratas embarazadas. Si usted cree que puede quedar embarazada,  
le pediremos que no participe en este estudio. 
  
• 
Tomar ciertos medicamentos con colchicina puede hacer que subir demasiado su nivel de colchicina, 
especialmente si usted tiene problemas renales o hepáticos (consulte "Guía del Medicamento" para más 
información). 
• 
Incluso los medicamentos que usted toma por un corto período de tiempo, tales como antibióticos, 
pueden interactuar con colchicina y causar efectos secundarios graves o la muerte. Por favor díganos 
acerca de cualquier medicamento que usted necesita tomar para que podamos asegurarnos de que 
puede seguir utilizando colchicina. 
• 
Evite beber jugo de toronja, ya que puede interferir con la capacidad del cuerpo para desglosar colchicina 
  
Mantenga el medicamento fuera del alcance de los niños. 
  
 
11. Las pruebas de ADN. Si nos permite estudiar su ADN, lo vamos a utilizar para la secuenciación del genoma. La 
secuenciación del genoma es una prueba que nos podrían dar diferentes tipos de resultados. Estos incluyen: 
a. Podríamos identificar cambios en los genes que están relacionados con el metabolismo y el peso corporal.  
b. Podríamos identificar cambios en los genes que contribuyen a otras enfermedades o problemas. 
c. Podríamos identificar los cambios en los genes que no son conocidos por causar ninguna enfermedad. Estos son 
conocidos como variaciones normales. 
d. Podríamos encontrar cambios en los genes que son nuevos y de importancia clínica incierta. Esto significa que no 
se sabe si podrían causar o contribuir a una enfermedad o si son variaciones normales. 
  
No todos los cambios genéticos tendrán implicaciones para la salud de su familia. Los cambios en los genes que 
tienen implicaciones para la salud de su familia: 
  
1. Ya han causado problemas de salud. 
2. Pueden causar un problema de salud en el futuro. 
 
Uno de los objetivos de este estudio es identificar los cambios en los genes que pueden estar implicados en la 
obesidad. Esta investigación puede tomar años. Sin embargo, si se identifica una causa genética o la causa probable 
de la obesidad , con su permiso, nos pondremos en contacto con usted. Por favor, háganos saber su preferencia con 
sus iniciales en una de estas dos declaraciones: 
  
______ Me gustaría ser contactado con la información sobre los avances de este estudio y contactado acerca de 
cualquier resultado relacionado con la obesidad. Entiendo que esta investigación llevará años y que una anormalidad 
específica no se puede identificar en mí. 
  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  10  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
______Por favor no se contacte conmigo acerca de la marcha de este estudio o cualquier cambio de genes 
específicos relacionados con la obesidad.  
 
Si detectamos un cambio genético que podría ser importante para usted, entonces vamos a tener que confirmar este 
resultado en un laboratorio certificado. Por esta confirmación, le pediremos una nueva muestra de ADN a usted. En la 
mayoría de los casos esto implicará la obtención de una pequeña muestra de sangre (1-2 cucharaditas). En algunos 
casos podemos obtener suficiente ADN para confirmar un cambio genético por limpiando el interior de la mejilla. 
Usted puede decidir, si desea hacerlo más adelante, si nos comunicamos con usted con la información de que hemos 
encontrado una posible diferencia genética importante. 
  
La identificación de cambios genéticos que no están relacionados con la condición que se está estudiando, se conoce 
como información médica incidental. 
  
Vamos a encontrar cambios genéticos en todo el mundo que estudiamos, pero estamos mirando sólo específicamente 
para los genes relacionados con el metabolismo y el peso corporal. No vamos a analizar su ADN para los cambios que 
no están relacionados con el metabolismo y el peso corporal. Aun así, algunos cambios en los genes no relacionados 
con el metabolismo y el peso corporal se detectarán. 
  
Nosotros sólo le informaremos de los cambios que tienen importancia médica urgente y se beneficiarían de un 
tratamiento médico temprano. Un ejemplo de esto sería un cambio en el gen que causa cáncer y en la que se 
beneficiaría de la detección temprana. No le informará de todos los cambios en los genes que tienen inciertas 
implicaciones para la salud. Por ejemplo no vamos a informar de los cambios genéticos que predisponen a los 
individuos sólo a la enfermedad. Un ejemplo de esto sería un cambio en el gen que influye en el riesgo de 
enfermedades del corazón, pero en el que el desarrollo de la enfermedad depende de muchos factores genéticos y no 
genéticos (tales como la dieta y el tabaquismo). Si nos encontramos con un cambio en un gen que es importante 
para la salud de su familia, sólo le daremos los resultados si el cambio ha sido confirmado por un laboratorio 
certificado. Para asegurarse de que no se ha producido un error, tendríamos que obtener una nueva muestra de ADN 
a partir de que se confirmen los resultados experimentales. 
  
Además de saber lo que encontramos, nos gustaría que conociera las limitaciones de la secuenciación del genoma y 
lo que no vamos a ser capaces de decirle acerca de los cambios que encontramos. 
  
1. No todos los cambios en los genes que causan la enfermedad serán detectados. 
2. Algunos de los cambios que no se conocen actualmente para causar problemas de salud podrían causar  
problemas de salud en el futuro. No podemos prometer tener la capacidad de decirle a usted acerca de esos 
cambios en el futuro. 
3. No le dirá acerca de cambios en los genes que no se sabe que tienen consecuencias para la salud, ni vamos a 
informarle sobre cambios en los genes que sólo tienen consecuencias reproductivas. 
4. Esta secuenciación de genes no puede ser sustituido por las pruebas de diagnóstico recomendado por otro 
médico. 
  
 
 
Por favor, coloque sus iniciales en todas las siguientes declaraciones para indicar que usted entiende la medida en 
que le informaremos sobre los cambios genéticos accidentales que encontremos: 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  11  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
______ Entiendo, que voy a estar informado sólo de cambios genéticos que los investigadores implicados 
en este estudio piensen que son urgentemente importantes para la salud de mi familia y que el 
conocimiento de estos cambios tiene el potencial de un beneficio significativo para mí o mi 
familia. 
 
______ Entiendo que los investigadores no van a buscar específicamente cambios en los genes no 
relacionados con el metabolismo y el peso corporal, y que la identificación de otros genes que 
causan enfermedades sólo ocurrirá por casualidad dependiendo del análisis que se realiza. 
 
______ Entiendo perfectamente que a pesar de que podrían tener consecuencias de salud o 
reproductivas, no se me hablará de todos los cambios genéticos identificados que no están 
relacionados con el metabolismo y el peso corporal. 
 
Si se detecta un cambio en el gen no relacionado con el metabolismo y el peso corporal y los investigadores 
sentimos que cumple con los requisitos de tener importancia médica urgente para que usted se beneficie de un 
tratamiento médico, a continuación, se le dará la opción para aprender o no aprender acerca del cambio genético 
encontrado. Usted puede elegir no ser contactado en absoluto si esa es su preferencia. Una excepción a su 
capacidad de elegir si desea o no saber acerca de un cambio en un gen, sería un cambio en un gen que los 
investigadores consideran que es de vital importancia para su salud. Un ejemplo de esto sería un cambio en el 
gen que tiene una alta probabilidad de causar cáncer o una enfermedad para la cual el tratamiento temprano 
sería beneficioso. Antes de confirmar el resultado en un laboratorio clínico nos pondremos en contacto con usted 
para obtener una nueva muestra de ADN. 
 
Si usted tiene un cambio en un gen con urgentes implicaciones para la salud, el NIH confirmará el cambio 
genético presente en uno de los miembros de su familia. Discutiremos los resultados con usted para que pueda 
saber si alguien más en su familia podría ser un portador de este mismo cambio. Podemos ayudarle a organizar 
las pruebas que haya que hacer, pero el NIH no podemos prometer realizar o pagar por las pruebas clínicas 
necesarias para confirmar o determinar quién más en su familia puede tener este cambio en su ADN. 
  
Una vez que se confirma un cambio en un gen, vamos a discutir los resultados con usted y hacer 
recomendaciones sobre apropiado seguimiento médico. El NIH no puede prometer realizar o pagar por los 
exámenes médicos recomendados o evaluaciones. 
  
Es posible que un cambio genético no se confirmará en las pruebas posteriores. Esto podría ser debido a un error 
en la secuenciación de ADN o un error en el procesamiento del ADN o líneas celulares. Aunque es agradable para 
Ud. que no se confirme el problema, esto puede causar un poco de ansiedad y preocupación que de otra manera 
no habría experimentado. 
  
Por favor, háganos saber sus preferencias colocando sus iniciales en una de las siguientes afirmaciones: 
  
______ Yo QUIERO ser re-contactado si se descubren variantes genéticas con consecuencias urgentes 
para la salud, durante esta prueba de investigación. 
  
______ NO deseo volver a ser contactado si se descubren variantes genéticas con consecuencias 
urgentes para la salud durante esta prueba de investigación. Entiendo que una excepción a esta 
elección, como se describió anteriormente, se hará para un cambio en el gen de importancia 
médica fundamental. 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  12  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
Riesgos emocionales y psicológicos de la prueba de ADN. La identificación de los cambios en los genes 
puede causar problemas emocionales y psicológicos. En algunas situaciones se podría recomendar asesoría 
psicológica. 
  
1. Aprender sobre el riesgo de enfermedad que en su familia puede ser angustiante. 
2. Aprender que algo que sucede en un gen suyo, puede no suceder en su hijo, puede ser angustiante. 
3. Otros miembros de su familia podrían ponerse molestos al saber que ellos pueden estar en riesgo de un 
trastorno debido a su participación en este estudio. 
  
Ud. Puede permanecer falsamente tranquilo acerca de su estado de salud si nosotros no le reportamos ningún 
cambio en su caso. 
  
Otros riesgos de las pruebas genéticas. Si confirmamos un cambio genetico en su ADN en un laboratorio de 
diagnóstico, esta información será parte de su expediente médico en el NIH. Algunas personas se preocupan de 
que la información acerca de ellos de sus registros médicos podrían ser dadas a conocer. Posibles problemas 
incluyen el seguro o la discriminación laboral. Medidas para proteger la confidencialidad de su información  se 
describen a continuación. Estos problemas también pueden ocurrir si usted divulga su propia información o 
acepta que sus registros de investigación sean liberados. 
  
Hay leyes estatales y federales que protegen contra la discriminación genética. Una ley federal llamada la Ley de 
No Discriminación por información Genética (GINA), generalmente hace que sea ilegal que las compañías de 
seguros de salud, planes de salud de grupo, y la mayoría de los empleadores discriminen contra usted basado en 
su información genética. Según esta ley, las compañías de seguros de salud o planes de salud de grupo (hasta el 
21 de mayo de 2010) no puede solicitar su información genética, o utilizarlo para tomar decisiones sobre su 
elegibilidad o primas; y los empleadores no pueden utilizarlo en la decisión de contratar, promover, ni puede 
despedirlo, o en el establecimiento de los términos de su empleo (a fecha de 21 de noviembre 2009). 
  
Tenga en cuenta que esta ley federal no le protege contra la discriminación genética por las compañías que 
venden seguros de vida, seguro de invalidez, o un seguro de cuidado a largo plazo. 
 
Este enlace contiene detalles sobre esta política: 
http://www.genome.gov/Pages/PolicyEthics/GeneticDiscrimination/GINAInfoDoc.pdf 
  
Usted puede preguntar a su equipo de investigación para obtener información adicional o una copia de la Ley de 
Discriminación por Información Genética de 2008 documento informativo. 
  
Los estudios genéticos pueden descubrir relaciones familiares inesperados. Por ejemplo, es posible que podamos 
enteramos de que un miembro de la familia no es el hijo biológico de los padres con los que él o ella vive (por 
ejemplo, debido a la adopción). No proporcionaremos normalmente este tipo de información a cualquier miembro 
de la familia o al médico de referencia. Sin embargo, podemos hacer excepciones en circunstancias 
extraordinarias si esta información se requiere para la atención médica de las personas involucradas. Si estamos  
convencidos de que esto es necesario, vamos a proporcionar la información al médico que proporciona la 
atención médica al paciente 
   
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  13  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
 
 
El uso de muestras almacenadas y datos 
  
Investigaciones futuras ADN. Actualmente tenemos la intención de secuenciar los genes conocidos. Esto 
representa sólo alrededor del 1% de su secuencia de ADN. En el futuro podemos secuenciar otras partes de su 
ADN, y, finalmente, podemos secuenciar completamente su ADN. Estos estudios adicionales pueden ocurrir años 
a partir de ahora. Algunas partes de su ADN pueden ser enviadas a otros laboratorios para pruebas específicas. Si 
esto se hace el ADN será codificado y no tendrá su nombre en la muestra o en el papeleo que va al laboratorio. 
En caso de retirarse de este estudio, vamos a mantener su ADN para el análisis a menos que usted nos pida 
destruir las muestras de AND. 
  
Por favor, coloque su inicial en una de las siguientes tres declaraciones relativas a la investigación futura: 
 
______ ADN puede ser utilizado para otros tipos de futuras investigaciones relacionadas con la salud. Esta 
investigación no se limita a los estudios relacionados con la obesidad, el metabolismo y el peso corporal. 
Esta prueba puede realizarse por laboratorios de investigación que no se encuentran en el NIH. Autorizo 
el uso de estas muestras sin mi consentimiento adicional. Entiendo que no se pondrán en contacto si se 
utilizan estas muestras en el futuro. 
  
______ Entiendo que las muestras genéticas recogidas durante estas visitas NIH serán guardados y utilizados 
para futuras pruebas experimentales relacionadas con la obesidad, el metabolismo y el peso corporal. 
Esta prueba puede realizarse por laboratorios de investigación que no se encuentran en el NIH. NO 
autorizo el uso de estas muestras para ningún otro fin sin mi consentimiento adicional. Debo ser 
contactado y dar consentimiento si estas muestras se van a utilizar en el futuro. 
  
______ No utilice mi ADN para futuros estudios más allá de los descritos anteriormente en este formulario de 
consentimiento. 
  
Futuras investigaciones con muestras de sangre. Nuestros planes específicos de investigación se han 
resumido en este formulario de consentimiento. En el curso de la investigación, vamos a obtener muestras de 
sangre. Si bien podemos hacer algunas de nuestras pruebas de inmediato, es posible que desee almacenar sus 
muestras de sangre en el congelador para futuros estudios. Además, cierta información se almacenará en su 
expediente médico. En el futuro, es posible que sus muestras de sangre o registros médicos serán utilizados para 
otros fines de investigación que no se describen específicamente en este formulario de consentimiento. Si se hace 
esto, las muestras serán codificadas, y no serán identificados por su nombre. Estas muestras pueden ser 
almacenadas en un lugar separado (llamado un repositorio) que se especializa en el almacenamiento de muestras 
clínicas. Usted tiene la opción, en el futuro, de solicitar que estas muestras no se utilicen para hacer más 
ensayos. Además, es posible que alguna información obtenida de estos estudios serán publicados en la literatura 
médica. Sin embargo, su identidad no será incluida en cualquier publicación. 
 
 
 
 
 


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  14  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
Por favor, coloque su inicial en una de las dos afirmaciones siguientes: 
  
______ Entiendo que las muestras recogidas durante estas visitas NIH serán guardadas y utilizadas para futuros 
ensayos experimentales relacionados con el peso corporal, y/o el metabolismo. Esta prueba puede 
realizarse por laboratorios de investigación que no se encuentran en el NIH. Autorizo a otros usos de 
estas muestras sin mi consentimiento adicional. Entiendo que no se pondrán en contacto si se utilizan 
estas muestras en el futuro. 
  
______ Entiendo que las muestras recogidas durante estas visitas NIH serán guardadas y utilizadas para futuros 
ensayos experimentales relacionados con el peso corporal, y/o el metabolismo. Esta prueba puede 
realizarse por laboratorios de investigación que no se encuentran en el NIH. NO autorizo cualquier otro 
uso de estas muestras sin mi consentimiento adicional. Debo ser contactado y dar consentimiento si 
estas muestras se van a utilizar en el futuro. 
  
Durante todo el proceso de estudio y después, la confidencialidad de los participantes será protegida mediante el 
uso de códigos y números de historia clínica en la grabación de su información y resultados de pruebas. Sólo el 
personal médico involucrado en este estudio tendrán acceso a los nombres de los participantes, resultados de 
exámenes, y los números de código de los pacientes. 
  
Usted tiene que ser consciente de que la secuencia de ADN es como una huella digital. Teóricamente si suficiente  
información de la secuencia de ADN está disponible, alguien podría identificarlo a Ud. en base a su secuencia de 
ADN. Para facilitar la investigación genética, la información de su secuencia de ADN se puede depositar en otras 
bases de datos. En este caso, a menos que tengamos su permiso, vamos a depositar los datos de una manera 
que no permita que alguien le identifique. Por favor, comprenda que esta información no se puede eliminar una 
vez que se deposita. 
   
Por favor, coloque su inicial en una de las siguientes casillas: 
  
______ No quiero que los datos de secuencia de ADN sean depositados en cualquier base de datos que no sea la 
que está asociada con este estudio. 
______ Mis datos de secuencias de ADN pueden ser depositados en las bases de datos que limitan el acceso a la 
IRB (comité de ética) Investigadores aprobados. 
______ Mi secuencia de ADN puede ser depositada en una base de datos que está disponible sólo para los 
científicos, pero que no requiere la aprobación del IRB de estudios de investigación. Entiendo que alguien 
teóricamente me podía identificar de esta información. 
  
Los beneficios potenciales de la participación 
  
Tenemos la esperanza de que su participación en este estudio proporcionará pruebas acerca de si la colchicina ayudará 
parámetros metabólicos en individuos obesos. Sin embargo, no puede beneficiarse directamente de participar en este 
estudio. Al encontrar anomalías en cualquiera de sus resultados de la prueba, se le notificará y recibirá una copia para 
ayudarle en la búsqueda de una mayor evaluación médica. Esta información puede o no mejorar su salud.   
 
 
  


 
  
CONTINUATION SHEET for either: 
  MEDICAL RECORD 
NIH 2514-1, Consent to Participate in A Clinical Research Study 
 
NIH 2514-2, Minor Patient’s Assent to Participate In A Clinical Research Study 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  15  of 17 pages 
 
 
 
 
PATIENT IDENTIFICATION 
CONTINUATION SHEET for either: 
 
NIH-2514-1 (10-84) 
 
NIH-2514-2 (10-84) 
 
P.A.: 09-25-0099 
 
Derecho de revocación y Condiciones de retiro anticipado 
  
Usted puede retirarse del estudio en cualquier momento y por cualquier motivo y sin pérdida de beneficios o privilegios a 
los que tiene derecho. 
  
La discusión de los nuevos hallazgos con usted 
  
Después de que todos los participantes hayan completado el estudio, se le informará sobre cual medicina tomó y una vez 
que el estudio esté totalmente analizado, le permiten saber si la colchicina puede ayudar con la inflamación y la 
resistencia a la insulina. No hay plan general para compartir los resultados de sus pruebas individuales con usted. Sin 
embargo, si algún hallazgo sugiere que tiene un problema médico, vamos a proporcionar esta información a usted y a su 
proveedor de atención primaria. Usted puede solicitar una copia de sus pruebas de laboratorio de rutina si lo desea. 
  
 
 
Terminación de Estudios 
  
Se le puede pedir terminar su participación en este estudio en cualquier momento, si creemos que la continuación en él 
no es lo mejor para su interés médico o si no puede cumplir con los requisitos del estudio. 
  
 
Alternativas a la Participación 
  
La alternativa a este estudio es no participar. Usted puede ser elegible para otros estudios en los NIH. Usted puede 
aprender más sobre ellos a través de www.clinicaltrials.gov. 
  
Compensación 
Usted será compensado por el tiempo y los inconvenientes asociados a la participación según las directrices de 
compensación para voluntarios de investigación del NIH. La compensación para completar todas las pruebas que se han 
descrito anteriormente es: $100 por la visita de selección de pacientes ambulatorios, $50 por la visita de seguridad, y de 
$300 por cada una de las visitas inicial, final y la opcional. La cantidad total que usted podría recibir por la participación si 
completa todas las partes de este estudio es de $1050. 
  
Conflicto de intereses 
  
El NIH y los miembros de este equipo de investigación no tienen ningún interés financiero en relación con este estudio de 
investigación. 
  
Publicación de Resultados de Investigación en: www.ClinicalTrials.gov 
  
Una descripción de este ensayo clínico estará disponible en http://www.Clinicaltrials.gov, como lo requiere la ley de 
Estados Unidos. En esta pagina de web no incluirá información que pueda identificarlo. En la mayor parte del sitio Web 
incluirá un resumen de los resultados. Usted puede buscar en este sitio web en cualquier momento. 
  
______ He recibido una copia del formulario de consentimiento firmado.


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  16  of 17 pages 
 
 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
INFORMACIÓN PERTINENTE ADICIONAL 
 
1. Confidencialidad. Cuando los resultados de un estudio de investigación del NIH se dan a conocer en revistas 
médicas o reuniones científicas, no se menciona la identidad de los participantes. En la mayoría de los casos, el NIH no 
divulgará ninguna información sobre su participación en la investigación a menos que usted otorgue su permiso por 
escrito. No obstante, si usted firma una autorización de divulgación de información, por ejemplo, a una empresa 
aseguradora, el NIH le proporcionará a ésta información de su expediente médico. Esta información podría influir (en 
forma favorable o desfavorable para usted) la disposición de la aseguradora a venderle el seguro.  
 
La Ley Federal de Protección de la Vida Privada (Federal Privacy Act) protege el carácter confidencial de sus expedientes 
médicos en el NIH. Sin embargo, es importante que sepa que esta ley permite la divulgación de cierta información de su 
expediente médico sin su autorización, por ejemplo, si lo solicitan la Administración de Alimentos y Medicamentos (FDA), 
los miembros del Congreso, los agentes encargados del cumplimiento de la ley o las organizaciones autorizadas para 
efectos de acreditación hospitalaria.  
 
2. Normas sobre lesiones relacionadas con la investigación. El Centro Clínico le dará atención médica a corto 
plazo para cualquier lesión que se deba a su participación en una investigación que se realice allí. En general, ni los 
Institutos Nacionales de Salud, ni el Centro Clínico, ni el gobierno federal le darán atención médica a largo plazo ni 
indemnización económica por lesiones relacionadas con la investigación. Sin embargo, usted tiene derecho a buscar una 
compensación legal si cree que la lesión justifica dicha medida.  
 
3. Pagos. El monto del pago que reciben los voluntarios de investigación se rige por las normas de los Institutos 
Nacionales de Salud. En general, a los pacientes no se les paga por participar en los estudios de investigación en los 
Institutos Nacionales de Salud. Se le ofrecerá el reembolso de gastos de viaje y viáticos según las pautas del NIH.  
 
4. Problemas o preguntas. Si hay algún problema o usted tiene una pregunta con respecto a este estudio, a sus 
derechos como participante en un estudio de investigación clínica o a cualquier lesión relacionada con la investigación, 
debe comunicarse con el Investigador Principal, Jack A. Yanovski, MD, PhD; Building (Edificio) 10, Room (Sala) 1-3330, 
Teléfono: (301) 496-4686 o el Investigador Asociado Principal, Andrew Demidowich, MD; Building 10, Room 1-3330, 
Teléfono: (301) 496-4686.  
 
También puede llamar al representante de los pacientes del Centro Clínico, al teléfono (301) 496-2626.  
 
5. Documento de consentimiento. Le sugerimos que conserve una copia de este documento para consultarla 
posteriormente. 


 
  
CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY 
   MEDICAL RECORD 
•  Adult Patient or    •  Parent, for Minor Patient 
 
STUDY NUMBER: 
14-CH-0119 
CONTINUATION:  page  17  of 17 pages 
 
 
 
PATIENT IDENTIFICATION 
CONSENT TO PARTICIPATE IN A CLINICAL 
 
RESEARCH STUDY (Continuation Sheet) 
 
•  Adult Patient or   •  Parent, for Minor Patient 
 
NIH-2514-1 (07-09) 
 
P.A.: 09-25-0099 
 
File in Section 4:  Protocol Consent 
 
 
COMPLETE LAS CASILLAS CORRESPONDIENTES A CONTINUACIÓN: 
 
A. Consentimiento de un paciente adulto. 
B. Permiso otorgado por el (los) padre(s) de un paciente 
menor de edad. 
He leído la explicación relacionada con este estudio y he tenido la 
oportunidad de comentarla y hacer preguntas. Por este medio otorgo mi 
consentimiento para participar en este estudio. 
He leído la explicación relacionada con este estudio y he tenido la 
oportunidad de comentarla y hacer preguntas. Por este medio otorgo 
permiso para que mi hijo participe en este estudio. 
(Anéxese el formulario NIH 2514-2, Asentimiento de un menor de edad, 
si corresponde.) 
 
  
 
 
  
 
Firma del paciente adulto o su representante  legal       Fecha 
 
 
 
Nombre en letra de imprenta 
Firma del (los) padre(s) o del tutor legal 
Fecha 
 
 
 
Nombre en letra de imprenta 
C. Asentimiento verbal de un niño (si corresponde)  
Se le explicó a mi hijo la información contenida en el presente documento y mi hijo está de acuerdo en participar en el estudio. 
 
 
 
  
 
 
 
 
Firma del (los) padre(s) o del tutor legal 
Fecha  
Nombre en letra de imprenta 
EL USO DE ESTE DOCUMENTO DE CONSENTIMIENTO ESTÁ APROBADO 
DESDE EL 24 DE ENERO DE 2018 HASTA EL 24 DE FEBRERO DE 2019.  
 
 
 
 
  
 
 
  
 
Firma del Investigador 
Fecha 
 
 
 
Nombre en letra de imprenta 
Firma del testigo 
Fecha 
 
 
 
Nombre en letra de imprenta