Clinical trial NCT02494141
Conditions: Polycystic Kidney, Autosomal Dominant
Sponsor: University of Colorado, Denver
Start date: 2015-11-12; Completion date: 2021-02-01
Enrollment: 68 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The proposed research will determine the effectiveness of curcumin for improving the health and function of arteries in children and young adults with autosomal dominant polycystic kidney disease (ADPKD). The study also will provide insight into how curcumin improves artery health by determining the physiological mechanisms (biological reasons) involved and offer exploratory evidence if curcumin can slow kidney growth. This will be done by comparing these measurements in children and young adults who are randomized to receive either curcumin or placebo for 1 year.

Detailed description:
Although often considered to be a disease of adults, complications of autosomal dominant polycystic kidney disease (ADPKD) begin in childhood. While ADPKD causes the continued growth of multiple kidney cysts that ultimately result in loss of kidney function, the leading cause of death among patients with ADPKD is cardiovascular disease. Treatment options to prevent cardiovascular disease in adults with ADPKD are limited, thus childhood may be an important time to reduce risk. Curcumin is a safe, naturally occurring substance found in the Indian spice tumeric, which is in curry powder. The proposed research will determine the effectiveness of curcumin for improving the health and function of arteries in children and young adults with ADPKD. The study also will provide insight into how curcumin improves artery health by determining the physiological mechanisms (biological reasons) involved and offer exploratory evidence if curcumin can slow kidney growth. This will be done by comparing these measurements in children and young adults who are randomized to receive either curcumin or placebo for 1 year.

Arms: arm 1: 25/mg/kg per day for 1 year. arm 2: Equivalent placebo for 1 year.
Interventions: intervention 1: Curcumin intervention 2: Placebo
Intervention descriptions: intervention 1: Dietary Supplement intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
 
Study Protocol and Statistical Analysis Plan  
Project Title: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD  
NCT Number: NCT02494141 
Version Date: 03/12/2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol #:  15-0902 
Project Title: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD  
Principal Investigator: Kristen Nowak, Ph.D. 
Version Date: 03/12/2020 
 
Specific Aims 
 
Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic disease, 
affecting more than 600,000 Americans 1,2.  Although often considered to be a disease of adults, 
complications of ADPKD begin in childhood 3.  While the hallmark of ADPKD is the development and 
continued growth of multiple renal cysts that result in ultimate loss of kidney function 4, the leading cause of 
death among affected patients is cardiovascular in nature 1,2.  As much as 80% of all cardiovascular diseases 
(CVD) are associated with dysfunction and disorders of arteries 5.  Two of the greatest contributors are 
vascular endothelial dysfunction, most commonly assessed as impaired endothelium-dependent dilation 
(EDD), and stiffening of the large elastic arteries (aorta and carotid arteries) 6.  Importantly, both measures 
are independent predictors of future cardiovascular events and mortality 7-10.   
 
Adults with ADPKD demonstrate impaired EDD 11-13 as well as large elastic artery stiffening 14 , even in the 
absence of hypertension.  The mechanisms by which arterial dysfunction occurs in ADPKD are incompletely 
understood, but appear to involve increased oxidative stress and inflammation 15-17.  My preliminary data in 
children/young adults with ADPKD support that arterial dysfunction develops very early in the course of the 
disease, as evidenced by impaired brachial artery flow-mediated dilation (FMDBA; a measure of EDD) and 
increased aortic pulse-wave velocity (aPWV; a measure of large elastic artery stiffness).  There are presently 
very limited treatment options for the prevention of cardiovascular disease in adults with ADPKD, thus, 
childhood/young adulthood may represent a critical therapeutic window.  
 
An increase in total kidney volume (TKV) precedes the decline in kidney function, which is typically delayed 
until the 4th decade of life in patients with ADPKD, and TKV is a prognostic biomarker of future kidney function 
decline 18.  Thus, a decrease in rate of TKV growth, as measured by magnetic resonance imaging (MRI) is 
an important indicator of kidney disease progression early in the course of ADPKD.         
 
Curcumin is a safe, naturally occurring polyphenol found in the Indian spice turmeric that has a unique ability 
to activate transcription of key antioxidants, suppress inflammation, and reduce proliferation.  Curcumin 
reduces arterial dysfunction in various rodent models of vascular dysfunction 19,20, and my preliminary data 
demonstrate that it also reduces age-associated vascular dysfunction in humans.  Importantly, curcumin also 
slows cyst growth in kidney cells in vitro 21 and in vivo 22.  Thus, curcumin is a promising nutraceutical to slow 
progression of renal and cardiovascular disease in children with ADPKD.  However, there is presently no 
information available regarding the potential therapeutic benefits of curcumin to treat arterial dysfunction and 
slow kidney growth in this population.   
 
Accordingly, the primary aim of this application is to determine the efficacy of curcumin for improving FMDBA 
and reducing aPWV in 68 children/young adults with ADPKD.  A key secondary goal is to obtain insight into 
the mechanisms by which curcumin therapy may reduce arterial dysfunction.  Last, a third exploratory aim is 
to determine if treatment with curcumin slows kidney growth.  These aims will be tested in a double-blind, 
placebo-controlled, randomized clinical trial conducted in children/young adults aged 6-25 years with ADPKD. 
 
Hypothesis 1: Oral curcumin therapy will reduce vascular endothelial dysfunction (increase EDD) and large 
elastic artery stiffness in children and young adults with ADPKD as compared to placebo. 
 
Specific Aim 1: To determine non-invasively: a) FMDBA and b) aPWV before and after 12 months of oral 
curcumin (25 mg/kg/day) or placebo; and after 6 months in a sub-set of all local patients. 
 
Hypothesis 2: The improvements in arterial function observed with oral curcumin treatment will be associated 
with reduced oxidative stress and inflammation. 
 
Specific Aim 2: In a subset of patients aged 18-25 years, to measure aPWV and FMDBA during normal vs. 
reduced (via acute ascorbic acid infusion) oxidative stress, and to measure circulating/urine markers of 
oxidative stress and inflammation before and after 12 months of oral curcumin or placebo. 
 
Hypothesis 3: Oral curcumin therapy will reduce the rate of kidney growth in children and young adults with 
ADPKD as compared to placebo. 


 
Specific Aim 3: To quantify TKV measured with MRI before and after 12 months of oral curcumin or placebo. 
 
Impact on the field. This study has the potential to establish a novel, safe, and easy to deliver therapy for 
the treatment of arterial dysfunction, and possibly renal cystic disease, in an understudied population of 
children and young adults with ADPKD.  
 
Research Strategy 
 
Significance 
 
Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Cardiovascular Disease (CVD).  ADPKD 
is the most common lethal genetic kidney disorder 1,2.   While the hallmark of ADPKD is the development and 
continued growth of multiple renal cysts that result in ultimate loss of kidney function 4, the leading cause of 
death among affected patients is cardiovascular in nature 1,2.  The proteins encoded by the PKD-1 and -2 
genes, polycystin-1 and -2, are expressed in vascular endothelial cells and smooth muscle cells of all major 
vessels, resulting in extrarenal manifestations of the disease 23.  There are presently very limited treatment 
options for the prevention of CVD in patients with ADPKD.   
 
ADPKD in Children and Young Adults.  Although often considered to be a disease of adults, ADPKD begins 
in childhood 3 and can in fact be diagnosed in utero 24.  Even in children with ADPKD, evidence of CV 
abnormalities begin to manifest, such as elevated blood pressure and increased left ventricular mass index 25-
27.  There are presently very limited treatment options for the prevention of CVD in adults with ADPKD.  Thus, 
childhood/early adulthood may represent a critical therapeutic window to prevent future CV complications. 
 
Vascular Function and CVD.  As much as 80% of all CVD is associated with dysfunction and disorders of 
arteries 5.  Two of the greatest contributors are the development of vascular endothelial dysfunction, most 
commonly assessed as impaired endothelium-dependent dilation (EDD), and stiffening of the large elastic 
arteries 6, both of which independently predict of future cardiovascular events and mortality 7-10. 
 
Vascular Function in ADPKD.  Adults with ADPKD demonstrate impaired EDD 11-13 as well as large elastic 
artery stiffening 14 .  Endothelial dysfunction occurs early in ADPKD and has been detected in normotensive 
adult patients with preserved kidney function 11-13.  My preliminary data in children and young adults support 
that vascular dysfunction develops very early in the disease, as evidenced by impaired brachial artery flow-
mediated dilation (FMDBA; a measure of EDD) and increased aortic pulse-wave velocity (aPWV; a 
measure of large elastic artery stiffness).  Targeting vascular dysfunction early in the course of ADPKD is more 
likely to alter the long-term course of the disease compared to later intervention, thus strategies to reduce 
vascular dysfunction in children and young adults with ADPKD have the potential for huge clinical impact.   
 
Integrative Physiological Mechanisms of ADPKD and Vascular Dysfunction.  The mechanisms by which 
vascular dysfunction develops in ADPKD are incompletely understood; however, reduced nitric oxide (NO) 
bioavailability is a critical contributor 12,17 and a common mechanism of both impaired EDD and increased 
arterial stiffness 6,28.  In ADPKD, oxidative stress and inflammation are increased and contribute to the decline 
in NO bioavailability 15-17.  Oxidative stress is defined as excessive bioavailability of reactive oxygen species 
(ROS) relative to antioxidant defenses.  Physiological stimuli, including inflammatory signaling, promote 
oxidative enzyme systems to produce ROS, including superoxide anion (O2● -) 29.  Superoxide reduces 
bioavailability of nitric oxide (NO) by a) reacting directly with NO to form peroxynitrite (ONOO-), another ROS; 
or b) oxidizing the essential cofactor (tetrahydrobiopterin) for NO synthesis by endothelial nitric oxide synthase 
(eNOS) 30,31.  Of note, plasma levels of asymmetric dimethylarginine (ADMA), an important inhibitor of eNOS, 
are increased in adult ADPKD patients with preserved kidney function 17.  Inflammatory signaling can also 
directly reduce NO bioavailability by down-regulating eNOS activity 32.  In turn, increased ROS stimulate pro-
inflammatory gene transcription and protein expression via the redox-sensitive pro-inflammatory transcription 
factor nuclear factor κ B (NFκB), thus further promoting a pro-inflammatory cascade in a vicious cycle 33,34.  
 
Total Kidney Volume in ADPKD.  An increase in total kidney volume (TKV) precedes the decline in kidney 
function, which is typically delayed until the 4th decade of life in patients with ADPKD, and TKV is a prognostic 
biomarker of future renal insufficiency 18.  TKV is a critical marker of disease progression in children with 
ADPKD, as renal function remains normal in nearly all affected children despite marked changes in kidney 
structure 3.  Thus, a decrease in rate of TKV growth, as measured by magnetic resonance imaging (MRI) is 
an important indicator of renal disease progression early in the course of ADPKD.         
 
Therapeutic Potential of Curcumin.  Curcumin, from the plant curcuma longa, is a safe, naturally occurring 
polyphenol found in the Indian spice turmeric that has long been used in traditional Indian medicine (see below 


for safety information).  In vivo, supplementation with curcumin improves physiological function in animal 
models of various diseases 35-37.  Although the exact mechanism of action is unknown, curcumin suppresses 
both oxidative stress and inflammation in vitro and in vivo 38-42.  Consequently, curcumin has been proposed as 
a safe and novel nutraceutical for intervention in several disease states 43. 
 
Curcumin and Vascular Dysfunction.  Curcumin administration reduces vascular dysfunction (increases 
EDD and/or reduces arterial stiffness) in rodent models of hypertension 20, diabetes 36,37, and aging 42.  These 
improvements are associated with increased vascular NO bioavailability and arterial eNOS expression, 
reduced vascular oxidative stress (decreased ROS, reduced oxidative damage, and increased antioxidant 
enzymes), and increased activity of hemoxygenase-1, which can promote anti-inflammatory pathways 20,36,37,42.  
In addition, my preliminary data support that curcumin also reduces vascular dysfunction associated with 
aging in healthy humans, consistent with published FMDBA data in post-menopausal women 44.  However, 
there is presently no information available regarding the potential therapeutic benefits of curcumin to treat 
vascular dysfunction in ADPKD, including children and young adults.  
 
Curcumin and Total Kidney Volume.  Curcumin has been of interest in nephrology for over a decade as a 
potential treatment of acute kidney injury (AKI) or chronic renal impairment in various rodent models of 
disease.  In addition to reducing histological evidence of kidney damage 45-48, its use in these models is 
associated with reduced evidence of oxidative stress and increased antioxidant activity 46,49,50, as well as 
reduced activation of the pro-inflammatory transcription factor NFκB and its downstream target tumor necrosis 
factor-α (TNF-α), concomitant with an increase in the anti-inflammatory transcription factor peroxisome 
proliferator-activated receptor-γ (PPARγ) 48.  Notably, curcumin also slows cyst growth in vitro in a dose-
response manner, using both the Madin–Darby canine kidney (MDCK) cell cyst model and an embryonic 
kidney cyst model 21.  Similarly, in the Pkd-1 deletion mouse model, curcumin improves renal histology and 
reduces proliferative index, cystic index, and kidney weight (normalized to total body weight) 22.  Thus, 
curcumin may also decrease the rate of TKV growth in children and young adults with ADPKD.   
 
In summary, cardiovascular complications are the leading cause of death in adults with ADPKD and are 
characterized by vascular dysfunction, which occurs very early in the course of the disease.  Intervening in 
affected children and young adults may represent a critical therapeutic window for the prevention of future 
cardiovascular events and mortality.  Curcumin is a novel, safe, and easy to deliver therapy with the potential 
to treat arterial dysfunction (an independent predictor of future cardiovascular events and mortality), and 
possibly renal cystic disease, in an understudied population of children and young adults with ADPKD. 
 
Summary of Significance.  The biomedical significance of the proposed work includes: 
 
ADPKD is the most common life-threatening genetic disease; 
 
There is an urgent need to establish the efficacy of interventions that may minimize CVD risk in patients 
with ADPKD; 
 
Presently, there are very limited treatment options for the prevention of CVD in patients with ADPKD; 
 
Many interventions targeting traditional risk factors have not successfully reduced CVD risk in patients 
with ADPKD, despite their efficacy in the general population; 
 
Childhood and young adulthood may be a critical therapeutic window for the treatment of arterial 
dysfunction and renal cystic disease in ADPKD; 
 
In a subsample of participants 18-25 yrs, insight will be provided into the integrative physiological 
mechanisms using novel translational research techniques that are non- to minimally-invasive. 
 
Innovation 
 
The innovative features of this application include:  
 
1. Intervening early in the course of ADPKD with treatment in children/young adults (6-25 years of age); 
2. Assessing two major contributors to arterial dysfunction and CVD risk in ADPKD: vascular endothelial 
dysfunction and large elastic stiffness; 
3. Determining the efficacy of a novel nutraceutical (curcumin) that is an inexpensive, safe, naturally 
occurring, and easy to deliver substance; 
4. In a sub-group of 18-25 year olds, using a translational approach to determine the physiological 
mechanisms contributing to any improvements in vascular dysfunction with curcumin, including: 
a. functional in vivo assessment of the role of oxidative stress in arterial dysfunction using acute 
antioxidant administration  
b. measurement of urine/circulating markers of oxidative stress and inflammation, utilizing state of 


the art mass spectrometry methods 
5. Gaining exploratory evidence of the efficacy of curcumin to slow kidney growth, which will provide the 
basis for a future R01 application employing a longer treatment duration and larger sample size. 
 
Approach   
 
Subjects.  After obtaining their written informed consent (ages 18-25) or assent (ages 6-17; plus parental 
consent), children and young adults aged 6-25 years with a diagnosis of ADPKD, based on the presence of  
bilateral renal cysts when there is a positive family history 51, and normal renal function with an estimated 
glomerular filtration rate (eGFR) >80 mL/min/1.73 m2 (using CKid Schwartz bedside equation for ages 6-17 52 
and the CKD-EPI equation for ages 18-25 53) will serve as subjects.  Patients will undergo screening and 
vascular testing at the University of Colorado Denver Division of Renal Diseases and Hypertension Clinical 
Vascular Physiology Laboratory, which is part of the Clinical Research Unit.  A local contracted laboratory 
(Quest) and medical records will be used for screening for out of state participants.  The University of Colorado 
Denver ADPKD Center has successfully employed this approach in previous and ongoing ADPKD clinical 
studies 54,55, including a recently completed trial by the co-mentor (Dr. Cadnapaphornchai) in 110 children and 
young adults with ADPKD 56.  Laboratory analysis will be performed at the University of Colorado Hospital or 
by Quest, and mass spectrometry analyses will be performed in the iC42 Clinical Research & Development 
Center.  Renal magnetic resonance imaging (MRI) scans will be performed at the Brain Imaging Center.   
Major inclusion/exclusion criteria are presented in the table below (Table 1).  Those who drop-out/do not 
complete the study will be encouraged to undergo an end-of study visit which will include identical 
measurements to the ones planned for session 5. 
 
 
 
Table 1       Inclusion Criteria 
Exclusion Criteria 
 Aged 6-25 years 
 ADPKD diagnosis based on bilateral renal cysts 
+ positive family history 51 
 Normal renal function with an estimated 
glomerular filtration rate (eGFR) 
>80 mL/min/1.73 m2 (using CKid Schwartz 
bedside equation for ages 6-17 52 and the CKD-
EPI equation for ages 18-25 53) 
 Ability to provide informed consent or assent 
 Currently taking a curcumin supplement  
 Current smokers or history of smoking in the past 12 months 
 Marijuana use within 2 weeks prior to FMDBA and aPWV testing 
 Antioxidant and/or omega-3 fatty acid use within the past 4 weeks prior to 
FMDBA and aPWV testing and for the duration of the study 
 Alcohol dependence or abuse 
 History of hospitalization within the last 3 months 
 Active infection or antibiotic therapy 
 Pregnancy, lactation, or unwillingness to use adequate birth control 
 Body-mass index >95th percentile in ages 6-17 or >40 kg/m2 in ages 18-25 
(vascular measurements can be inaccurate if severely obese) 
 Inability to cooperate with/clinical contraindication for MRI including severe 
claustrophobia, implants, devices, or non-removable body piercings  
 
Experimental Design (Figure 1).  A 1-year randomized, placebo-controlled, double-blind design study with 
curcumin will be conducted.  Subjects will undergo telephone and laboratory screening for inclusion/exclusion 
criteria and will then be randomly assigned to either curcumin or placebo.  Members of the investigative team 
involved in the acquisition and analysis of data will be blinded to the treatment status.  Vascular function 
measurements will be made under supine, overnight fasted (water only) conditions before and after 1-year of 
the intervention, and at 6-months in local patients to reduce variability over time and better establish timeline of 
change.  Females who are post-pubertal will be scheduled during the first week of their menstrual cycle, when 
estrogen and progesterone are lowest, minimizing the impact of hormonal variations on vascular function 57. 
 
 
Figure 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Session 5 
Mid-study Measurements            
(local patients only)  
Subjects randomly assigned to curcumin or placebo 
Preliminary screening by telephone; laboratory screening 
Baseline Measurements 
Baseline Measurements 
6 months curcumin 
Mid-study Measurements            
(local patients only)  
6 months placebo 
Post Measurements 
Post Measurements 
6 months placebo 
6 months curcumin 
Session 1  
Sessions 2 & 3 
Sessions 6 & 7 
Session 4 


In state subjects will come to the Clinical Vascular Physiology Laboratory (sessions 1, 2, 4, 5, and 6) or the 
Brain Imaging Center (sessions 3 & 7) on 7 separate occasions.  Out of state participants (approximately half) 
will travel twice to Colorado. Sessions 2 & 3 and then 6 & 7 will occur on consecutive days during the same trip 
(for a total of 2 out of state trips during the study).  Session 1 (and subsequent safety labs) will be 
arranged at a local contracted laboratory (Quest) for out of state participants.   
 
 
Session 1: Screening measurements  
 
Session 2: Baseline measurements 
 
Vital signs 
 
Blood sampling for measurement of circulating curcumin levels, serum creatinine, ALT and AST 
and urine sampling for markers of oxidative stress (all subjects); blood sampling for markers of 
inflammation (subset of subjects 18-25 years)  
 
FMDBA (EDD) and aPWV (arterial stiffness) (all subjects), with and without acute inhibition of 
oxidative stress via systemic i.v. infusion of ascorbic acid (subset of subjects 18-25 years) 
 
Endothelium-independent dilation to sublingual nitroglycerin (subset of subjects 18-25 years) 
 
Session 3: Baseline measurements 
 
Abdominal MRI for subsequent analysis of TKV (all subjects) 
 
Begin study treatment (curcumin or placebo) 
 
Session 4: Safety lab check  
 
Session 5: Mid-study measurement of FMDBA and aPWV for local (in state) patients only; safety lab 
check (all patients)  
 
Sessions 6 & 7 (month 12): Identical to Sessions 2 & 3 (note: subjects will not take a dose the a.m. 
prior to testing session to avoid any acute effects) 
 
Curcumin.  Curcumin will be delivered as a dose of 25 mg/kg/day rounded to the nearest 100 mg, delivered as 
powder measured in 100 mg and 500 mg scoops (LongvidaTM, Verdure Sciences).  The placebo will contain 
inert substances (soy lecithin, stearic acid, ascorbyl palmitate, carrot extract) of similar proportions and 
amounts as in the active powder.  The powder delivery will improve adherence, particularly among young 
children who may have difficulty swallowing capsules.   The powder will be delivered mixed with a choice of 
pudding yogurt, or other foods of similar consistency.  Absorption of LongvidaTM is the same when taken with a 
small amount of food compared with water or milk.   
 
Curcumin has been investigated extensively for safety and toxicity because of its use in foods.  Toxicology 
studies have been performed on the effects of curcumin in rodents and humans that are summarized below in 
the overall context of the present study.   
 
Background.  Curcumin is the active ingredient in the Indian spice turmeric and gives it a yellowish color.  It is 
found naturally in the root of the plant Curcuma longa and has traditionally been used for the prevention and/or 
treatment of ailments related to the skin, liver, gastrointestinal tract, and the common cold 58.  Epidemiological 
studies have shown that societies that regularly consume curcumin in their diet have markedly reduced 
mortality due to coronary heart disease 59.  More recently, curcumin’s potential benefits have been assessed in 
other pathologies such as cancer, arthritis, Alzheimer’s disease and hypercholesterolemia.  In addition, 
curcumin has been shown to attenuate oxidative stress and inflammation both in vitro and in vivo 38,39,41,42,60. 
 
History/Testing.  Because of its color, flavor and antioxidant-stabilizing abilities curcumin is commonly used in 
yellow mustard, pickles and sauces.  Curcumin has been used to flavor foods and treat ailments for over 5,000 
years and is generally recognized as safe (GRAS) by the FDA (this is also true specifically of LongvidaTM).  
Studies conducted in rats and humans using standard toxicology protocols have shown no toxic effects of 
curcumin in vivo at doses as high as 8 grams/day (8,000 milligrams/day), i.e., several-fold higher than the 
dose proposed in the present application 61-64.   
 
Human Studies.  Few side-effects of curcumin have been reported with doses up to 8-12 grams/day (8,000-
12,000 milligrams/day) of supplementation in adults 61,62,65 and children 64,66,67.  The few side-effects reported 
primarily involve gastrointestinal discomfort 61,65,67.  
 
 
Improving Bioavailability: Choice of Compound.  To enhance the bioavailability of curcumin, manufacturers 
have developed formulations that may prevent glucuronidation, as unprocessed curcumin is insoluble in water 
and quickly metabolized by glucuronidation.  The compound proposed in the current application is a solid lipid 
curcumin particle (SLCP, LongvidaTM, Verdure Sciences) that increases plasma levels of curcumin significantly 
compared to traditional formulations in healthy volunteers 64 and is safe in both this group and osteosarcoma 


patients, including children 64.  SLCP supplementation in rats with 720 mg/kg body mass/day, equivalent to 40 
g/day (40,000 mg/day) for a 60 kg person, for 90 days had no adverse effects 63.  
 
In summary: 1) curcumin is a naturally occurring and widely used spice in southeastern Asian cultures and 
poses only minimal risks at very high doses; and 2) all of the safety studies performed in adults and children 
have used maximal doses of curcumin that are significantly higher than those proposed in the present 
application (detailed rationale regarding doses and duration of treatment is below). 
 
Rationale for Proposed Dose (25 mg/kg/day), Frequency (once a day) and Duration (12 months)  
Dose (25 mg/kg/day) 
 Dosing is normalized to body mass to account for wide differences across the included age range. 
 This normalized dose is based off a 2,000 mg dose delivered to an 80 kg adult, which is similar to published  
work of others 61,62,64,67 and well below maximal dosing levels.  This dose has also been recommended by 
Verdure Sciences, who is providing the SLCP powder. 
 Additionally, 25 mg/kg/day was selected because 2,000 mg/day has been consistently shown to be both 
safe and well tolerated in adults 61,62,64, and children 64,67, is unlikely to elicit gastrointestinal discomfort 61,67, 
and improved vascular function in preliminary studies performed in aging adults (see Preliminary Results). 
 While older children and young adults could have instead been prescribed to swallow capsules, all 
participants will ingest the curcumin as powder mixed with pudding or yogurt, to standardize intake across 
all ages. 
 
Dosing Frequency (once a day) 
 The curcumin (or placebo) powder will be administered once a day in the morning for standardization.   
 
Duration of Treatment (12 months) 
 Given my previous experience with interventions to improve arterial function in the context of healthy aging, 
I expect 12 months to be a sufficient duration 68,69.  While I recognized that the duration is likely too short for 
a significant decrease in rate of TKV growth, any trend from this exploratory aim will be useful to design a 
future, longer duration R01 grant application. 
 Although my preliminary data (see below) support that curcumin has beneficial effects in healthy aging on 
FMDBA at 3 months, a 12 month treatment period was selected because 1) ADPKD may have a more 
severe effect on vascular function than healthy aging; 2) reversal of structural properties of the arterial wall 
associated with arterial stiffness may require a longer duration of treatment; 3) this allows for exploratory 
insight into changes in TKV, which is supported by cell and animal data 21,22. 
 I considered including multiple groups with different outcomes, including a shorter treatment length to 
evaluate vascular function; however, this design would greatly reduce power and further increase cost of the 
study.  Instead, I opted to add evaluation vascular function in local patients (~50% of the total n) at 6 
months, in addition to 12 months, in order to account for variations in adherence and changes in 
development over time (i.e. puberty) that may increase variability. 
 Importantly, I recognize that aPWV changes across puberty 70-72, whereas the available data suggest that 
FMDBA does not 73.  However, this should not limit the interpretation of the results as 1) randomization will 
ensure similar changes across the active and control groups; 2) puberty will be accounted for in statistical 
analysis; and 3) vascular measurements at 6 months in local patients will help account for such changes.        
 Curcumin has been tested extensively and used in the food/manufacturing industry.  It is a natural dietary 
component, and our proposed dose has been repeatedly shown to be well-tolerated and elicit no side 
effects.  Thus, there is no evidence to suggest the possibility of adverse effects associated with the 
proposed 12 months of increased intake of curcumin.   
 
Study Modifications to Account for COVID-19 Outbreak.  On account of COVID-19 and Institutional policies 
in place regarding work-related travel, the length of treatment of participants in may be extended due to 
extenuating circumstances.  The end-of-study visit may be delayed due to concerns over air travel, in which 
case participants will be asked to continue taking the curcumin/placebo, as they have been doing for the past 
year, and we will reschedule their end-of-study visit at the earliest time point that seems appropriate (hopefully 
within a couple of months).  We will obtain in-person data at this time, but will ask participants to go to our 
contract laboratory for the clinical labs at the planned 12 month time point if possible. We do not see any 
additional risk posed to participants by extending their treatment period, as curcumin already has a very 
favorable safety profile.   
 


Summary of risks associated with curcumin.  Based on preliminary studies (see below) and an extensive 
review of literature, the proposed doses of curcumin are both physiologically relevant and predicted to be well-
tolerated by the great majority of study participants.  The primary risk associated with curcumin 
supplementation is the possibility of temporary/transitory gastrointestinal distress (flatulence, constipation, 
diarrhea, nausea) in a very small percentage of individuals 61,65,67.  
 
Measurements. 
 
Screening Measures.  Subjects will undergo a medical history and physical exam, including growth 
parameters and Tanner staging 74-76, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and 
a pregnancy test for all female participants of possible childbearing potential (Tanner Stage 2 or higher).  
Serum creatinine will be measured for determination of eGFR using the CKid   Schwartz bedside equation for 
ages 6-17 52 and the CKD-EPI equation for ages 18-25 53.  A local contracted laboratory (Quest) and medical 
records will be used for out of state participants.  EMLA cream may be used as needed to numb the skin prior 
to drawing blood.     
 
Measures of Adherence and Safety: 
 
Adherence.  As we expect ~50% of all participants to be from out of state, progress will be reviewed with a 
monthly phone inquiry of medication supply.  Please note, due to the long history and prestige of University of 
Colorado PKD Center studies, our families have tremendous relationships with our research staff (i.e. 
investigators and research coordinators).  The co-mentor, Dr. Cadnapaphornchai, has successfully employed 
this approach in previous clinical trials in children/young adults with ADPKD that have included ~50% out of 
state patients 54,56.  We expect the minimal side-effects associated with curcumin to favor adherence.  
Participants will have powder mailed every 3 months and will also be asked to mail back the bottle for a volume 
check.   
 
Safety Checks.  While adverse events are not anticipated, a safety questionnaire will be administered over the 
phone monthly.  Serum creatinine, ALT and AST will be measured after 1, 6, and 12 months, and for those out 
of state, will be performed at a local contracted laboratory (Quest).  Home pregnancy tests will be required 
monthly for all girls of possible childbearing potential (>Tanner Stage 2).  All subjects will be given a digital 
blood pressure monitor (A&D Medical, UA767) with an appropriately sized cuff and the subject/parent will be 
instructed in its use.  Home blood pressures will be taken monthly and reported during phone safety checks.  
This approach has been successfully employed previously by the co-mentor, Dr. Cadnapaphornchai 54,56.    
 
Plasma Curcumin Concentrations will be assessed at baseline and 12 months by liquid chromatography-
tandem mass spectrometry (LC-MS/MS) at the University of Rhode Island 77.  Additionally, curcumin 
concentrations will be measured by the in red blood cells, the buffy coat, and plasma with the addition of citrate 
to prevent the degradation of metabolites.   
 
Randomization will be performed by the statistician, using a blocked randomization sequence, with 
stratification by age group (6-13 or 14-25 yrs). 
 
Outcome Measures.  The following measurements will be made at baseline and after 12-months of treatment: 
 
Primary (Functional) Outcomes (Specific Aim 1)  
 
Brachial Artery FMD and Endothelium-Independent Dilation.  FMDBA will be determined using high-
resolution ultrasonography (Toshiba Xario 200) as described originally by Celermajer et al. 78 and used 
recently by the applicant 68,79,80.  FMDBA is a widely used, non-invasive method inducing reactive hyperemia to 
assess endothelium-dependent dilation.  It is validated in children 78,81 and is mainly dependent upon NO 
production 82,83.  Brachial artery endothelium-independent dilation will be determined in the sub-group of 
participants aged 18-25 yrs by measuring brachial artery dilation for 10 minutes after administration of 
sublingual nitroglycerin (0.4 mg) 67,84,85.  This assessment is key to the interpretation that any improvements in 
dilation are indeed dependent upon endothelial production of NO rather than improved smooth muscle 
relaxation to NO 86.  The use of nitroglycerin is currently safely employed in an NIH-funded, IRB-approved 
protocol in adults with ADPKD at the University of Colorado Denver.  A commercially available software 
package (Vascular Analysis Tools 5.8.1, Medical Imaging Applications) will be used to acquire and analyze 
ECG-gated brachial artery diameters.  Doppler blood flow velocity will be obtained for estimation of shear rate, 
which will be entered as a covariate if indicated 87-89. 
 
Aortic Pulse-Wave Velocity.  aPWV will be determined as described in detail previously by applicant 69,90 and 
validated in children 71,91.  Briefly, a transcutaneous custom tonometer (Noninvasive Hemodynamics 


Workstation, Cardiovascular Engineering Inc.) will be positioned at the carotid and femoral arteries to non-
invasively assess aPWV, as distance/time between the foot of the arterial waveforms 92.  As a secondary index 
of arterial stiffness, ultrasound imaging of the carotid artery will also be performed for calculation of carotid 
artery compliance and the β-stiffness index (in conjunction with tonometry), as described previously 96,97.  The 
images will also be assessed for measurement of carotid artery intimal-medial thickness (IMT), which is used 
in the calculation of carotid artery compliance and the ß-stiffness index. 
 
Outcomes for Specific Aims 2 (Only in the sub-group aged 18-25 years (except for urinary markers)) 
 
Oxidative Stress-Associated Suppression of EDD and Large Elastic Artery Stiffness.  The influence of 
oxidative stress on FMDBA and aPWV (and carotid artery compliance) will be determined by infusing a 
supraphysiological dose of ascorbic acid (American Regent Labs) known to scavenge superoxide or 
isovolumic saline, as used previously by the applicant 68,93, and others 84,94-96.  This procedure is currently 
safely employed in an NIH-funded, IRB-approved protocol in adults with ADPKD at the University of Colorado 
Denver.  The infusion will be performed only if cannulation in a vein on the dorsal aspect of the contra-lateral 
hand is successful.  0.075 g ascorbic acid/kg fat-free mass dissolved in 150 mL of saline will be infused 
intravenously at 5 mL/min for 20 min, followed immediately by a “drip-infusion” at 0.5 mL/min over 60 min.  
Vascular measurements will be made during the “drip infusion” when peak plasma concentrations of ascorbic 
acid occur 84.  The difference in FMDBA and aPWV (and carotid artery compliance) during ascorbic acid vs. 
saline infusion indicates the modulation of EDD and arterial stiffness by oxidative stress 84,94.  These measures 
will be performed in the sub-group (18-25 yrs) only. 
 
Markers of Oxidative Stress.  Urinary 8-iso-prostaglandin F2α (8-isoprostane) and 8-hydroxy 2 
deoxyguanosine (8-OHdG) will be measured by LC-MS/MS as a markers of lipid peroxidation 97 and oxidative 
DNA damage 98, respectively, as oxidative damage is increased ADPKD 17.  While Aim 2 is primarily in a sub-
group aged 18-25 yrs, these oxidative stress measurements will be performed in all participants (6-25 yrs), as 
urine can be collected non-invasively.   
 
Inflammatory Markers.  Plasma C-reactive protein (immunoturbidimetric method) and plasma interleukin-6 
(ELISA; R&D Systems) will be measured by the University of Colorado Hospital as circulating inflammatory 
markers 79,99, as both are increased in ADPKD 16.  To minimize the amount of blood collected in children <18 
yrs, these measures will only be performed in the sub-group aged 18-25 yrs.   
 
Outcome for Specific Aims 3 
 
MRI Measurement of TKV.  A 1.5 Tesla Visart System (Toshiba America Medical Systems) or comparable 
system will be used for all studies.  Renal images will be acquired in similar manner and volumetric 
measurements determined as described for the CRISP study 100.  No contrast agents will be utilized for the 
study.  The radiologist, MRI study technicians and the applicant, who will calculate TKV, will be blinded 
regarding group assignment.  For analysis, DICOM images will be de-identified and evaluated by a single 
analyst (the applicant) using Analyze software (Analyze 9.0, Mayo Foundation, Rochester, MN).  To account 
for normal growth in children, TKV will be adjusted for height 56.  Feasibility of this aim is supported by the fact 
that the co-mentor, Dr. Cadnapaphornchai, recently completed an intervention study with MRI measurement of 
TKV in 110 pediatric and young adult patients with ADPKD 56.  In addition renal parenchyma (TKV – cyst 
volume) will be measured. 
 
Additional Blood Samples 
For subjects signing the Informed Consent Addendum, an additional 5 mL of serum and 9 mL of plasma in 
adults and an additional 1 mL of serum and 2 mL of plasma in children will be collected for future research.  In 
addition, 20 mL of whole blood will be collected from adult participants only.  PBMCs will be isolated from 
heparinized whole blood using Histopaque-1077 as described previously 106,107.  To provide mechanistic insight 
into biological pathways that may be altered by curcumin (for example, mammalian target of rapamycin 
(mTOR)-S6 kinase (S6K) signaling), the PBMCs will be washed and protein will be extracted for Western blot 
analysis.    
 
Expected Results.  In children/young adults with ADPKD, 12 months of curcumin compared to placebo will: 
 
 
Hypothesis 1:  
 ↑ FMDBA (↑ vascular EDD) 
 ↓ aPWV (↓ large elastic artery stiffness) 
 
Hypothesis 2 (Only in participants 18-25 years of age): 


● Have little or no effect on FMDBA and aPWV in the presence of ascorbic acid, whereas ascorbic acid is 
expected to significantly improve both of these measures in placebo-treated subjects, indicating a 
curcumin-mediated reduction in oxidative stress-related suppression of vascular function 
● ↓ urinary 8-isoprostane and 8-OHdG, indicating reduced systemic oxidative stress 
● ↓ plasma C-reactive protein and interleukin-6, indicating reduced systemic inflammation 
 
Hypothesis 3 
 Tend to ↓ the progression of TKV (adjusted for height), which can be examined further in a longer-
duration, larger sample size, future R01 grant  
 
Power Calculations and Statistical Analysis.  Power calculations are based on clinically meaningful 
differences in the primary outcomes (FMDBA and aPWV), limited published literature using curcumin in a 
healthy older population 44, and experience of the applicant regarding the variability of the proposed outcomes 
68,69,79.  A sample size of 27 in each group with have 90% power to detect a mean increase in FMDBA of 1.5%, 
given a standard deviation of 2.0 68, with α = 0.025, adjusted for two primary endpoints.  Akazawa et al. 44 
demonstrated in healthy post-menopausal women a ∆FMDBA of +1.5% with curcumin compared to a decrease 
in FMDBA of -0.2% in controls.  Similarly, a sample size of 27/group will have 90% power to detect a mean 
decrease of aPWV of 100 cm/sec given a standard deviation of 125 69 with α = 0.025, adjusted for two primary 
endpoints.  To account for a potential dropout of 20%, 34 subjects/group will be enrolled.    
 
A sub-sample size of 10 in each group (of 18-25 year olds) will have 89% power to detect a 50% reduction in 
∆FMDBA with ascorbic acid (given ∆FMD = +3.0+1.0% with ascorbic acid in the placebo group 68), with a two-
sided α = 0.05.  Aim 3 will be considered exploratory, thus power was not calculated.     
  
Differences between groups at baseline will be assessed by an independent t-test, and a linear mixed-effects 
model will be fit to compare curcumin vs. placebo (independent variable) with respect to change in outcomes at 
6 and 12 months (dependent variables), with covariates and potential confounders (including puberty) 
incorporated into the model.  This approach will account for the use of multiple time points and is flexible to 
missing (at random) data.  Although I do not expect different responses based on sex or race/ethnicity, and the 
study is not powered to assess these factors, stratified analysis will be performed and any trends will be noted 
and studied in a larger follow-up study.  Dropouts will be handled using an intent-to-treat analysis. 
 
Study Time Line.  I will use the initial 8 weeks to begin subject recruitment and screening.  The first subjects 
will begin treatment with curcumin or placebo in month 3 of the proposed overall 5-year funding period.  The 
last patients enrolled will complete the study by approximately month 54.  Vascular and MRI measurements 
will be performed over this period.  Mass spectrometry assays will be performed annually to detect any 
problems early in the course of the study.  Statistical analysis and manuscript preparation will be undertaken 
during the last 6 months (months 54-60).  This is an appropriate rate of subject enrollment and experimental 
testing based on previously completed intervention studies in this population (which also included ~50% out of 
state patients) by the co-mentor Dr. Cadnapaphornchai 54,56. 
 
Recruitment Plans.  Since 1985, the University of Colorado Denver has maintained an ADPKD registry and  
mailing list.  Included in this registry are children and young adult ADPKD patients from the Denver Metro Area 
and all over the United States.  In addition to the University of Colorado Denver registry, I will advertise through 
the national PKD Foundation.  The ADPKD center at the University of Colorado Denver has longstanding 
expertise and national recognition, and therefore, is able to attract ADPKD patients from all over the United 
States for clinical studies.  Of note, the University of Colorado Denver is currently the only group in the world 
performing research studies in children with ADPKD.  The feasibility of recruitment is supported by the recently 
completed intervention study performed by the co-mentor Dr. Cadnapaphornchai, which included 110 pediatric 
and young adult patients with ADPKD (including ~50% out of state) followed for a three-year period 56, and 
these participants will be recruited for the proposed research study.   
 
Potential Problems, Alternative Strategies, and Future Directions.  Although subject recruitment and 
retention always are challenges, I am confident in my ability to complete the study in the proposed timeline 
given our location in the densely populated Denver-Boulder metro area and our department’s 30 years of 
experience in studying patients from around the country with ADPKD, including children and young adults.  I 
should have few difficulties with the proposed experimental procedures and protocols as either a) I have 
expertise in the techniques in other populations; or b) the methodology is already established within our 
ADPKD research group, and I will be trained to perform these new skills by my mentorship team. 
 
I recognize that alternative approaches exist for examining the effects of curcumin in children and young adults 
with ADPKD.  For example, one alternative would be to undertake a larger study to examine harder 


cardiovascular endpoints than the intermediate outcomes proposed in the current application.  However, this 
approach requires very large sample sizes, and the validated endpoints of FMDBA and aPWV will provide initial 
insight that can guide a future larger-scale clinical trial using hard clinical endpoints.  Similarly, I acknowledge 
that long-term follow-up is required to determine if curcumin has beneficial effects into later adulthood, and this 
is also a potential future direction following this initial study.  I recognize that the proposed study duration and 
sample size will only provide a trend for any changes in TKV with curcumin, and such exploratory evidence will 
provide the basis for a future R01 application employing a larger sample size and treatment duration.   
 
Last, I recognize the possibility of negative data; however, such data are still important, as a recent state of the 
art review on prospective and novel treatments of ADPKD identified curcumin as a potential therapy 101, and 
either positive or negative results are critical in continuing to advance treatment options.  Importantly, the 
proposed Career Development plan will provide the scientific and professional skills required to conduct future 
randomized controlled trials in this patient population, and I will continue to pursue other novel interventions 
through small pilots and in conjunction with my collaborators performing pre-clinical research throughout the 
award’s duration.  In the event the study is negative, other potential therapies for a future R01 application 
include the mitochondria-targeted antioxidant MitoQ and metformin.  My training in epidemiology will also allow 
me to identify other targets for future clinical trials.  In addition, I will have a unique dataset of longitudinal 
changes in vascular function, oxidative stress, and TKV, which may generate novel hypotheses.              
 
Preliminary Results: all data are presented as mean+s.e. 
 
I. Vascular Endothelial Dysfunction in Children and Young Adults  
with ADPKD 
 
I assessed FMDBA in 9 children/young adults (ages 6-25 yrs) with ADPKD and normal kidney function, and 9  
age- and sex-matched healthy controls (16+2 years; 1M/8F).  Compared to 
the healthy control group, FMDBA was impaired (Figure 2) in the children and 
young adults with ADPKD, indicating vascular dysfunction very early in the 
course of the disease.  Baseline brachial artery diameter (3.1+0.09 [ADPKD] 
vs. 3.1+0.16 cm [control]) did not differ between groups.  Blood pressure 
(108+13/59+7 vs. 109+5/59+2 mmHg) and body-mass index (22.0+2.9 vs. 
21.6+1.4 kg/m2) also did not differ between groups.   
 
II. Large Elastic Artery Stiffness in Children and Young Adults  
with ADPKD 
 
I also assessed aPWV in the same 9 children 
and young adults with ADPKD and the same 
9 age- and sex-matched healthy controls.  
Compared to the control group, aPWV was 
greater (Figure 3), indicating increased large-
elastic artery stiffness even at a young age.  
Carotid artery β-stiffness index, a measure of 
local large-elastic artery stiffness, was also 
greater in the ADPKD group (Figure 4).  
Resting heart rate did not differ between groups (66+8 [ADPKD] vs. 63+2 bpm [control]).  
 
III. Curcumin to Treat Vascular Dysfunction 
 
My graduate laboratory has assessed the efficacy of curcumin therapy 
(same company and similar normalized dose as proposed: 2,000 mg/day, 
LongvidaTM, Verdure Sciences) to reduce age-associated vascular 
dysfunction.  Compared to placebo, FMDBA was improved (Figure 5) in 5 
healthy adults (65+3 years, 2M/3F) treated for 3 months with curcumin, as 
compared to placebo.  The curcumin was well tolerated in all participants 
without any adverse effects.  As aging is associated with impaired FMDBA 
similar to ADPKD, curcumin may also reduce vascular dysfunction in  
children/young adults with ADPKD.  Please note, aPWV and B-stiffness index were not assessed in this 
preliminary study, as it may require more time to change in response to an intervention.  
 
Human Subjects 
 
Figure 2 
Figure 5 
Figure 3 
 
Figure 4 


1. Risks to the Subjects 
 
a) Human Subjects Involvement and Characteristics. 
 
Subjects.  After obtaining their written informed consent (ages 18-25) or assent (ages 6-17; plus parental 
consent), children and young adults aged 6-25 years with a diagnosis of autosomal dominant polycystic kidney 
disease (ADPKD), based on the presence of bilateral renal cysts when there is a positive family history 51, and 
normal renal function with an estimated glomerular filtration rate (eGFR) >80 mL/min/1.73 m2 (using CKid 
Schwartz bedside equation for ages 6-17 52 and the CKD-EPI equation for ages 18-25 53) will serve as subjects 
will serve as subjects.  Patients will undergo screening and vascular testing at the University of Colorado 
Division of Renal Diseases and Hypertension Clinical Vascular Physiology Laboratory.  A local contracted 
laboratory (Quest) and medical records will be used for screening for out of state participants.  The University 
of Colorado Denver ADPKD Center has successfully employed this approach in previous and ongoing ADPKD 
clinical studies 54,55, including a recently completed trial by the co-mentor (Dr. Cadnapaphornchai) in 110 
children and young adults with ADPKD 56.   Laboratory analysis will be performed at the University of Colorado 
Hospital, and mass spectrometry analyses will be performed in the iC42 Clinical Research & Development 
Center.  Renal magnetic resonance imaging (MRI) scans will be performed at the Brain Imaging Center. 
 
To be eligible to participate in this research, volunteers must meet the following criteria:  
 
Inclusion Criteria: 
 
 
1) Aged 6-25 years (rationale: 6 was chosen as the lower age limit, as children younger than 6 may have 
difficulties remaining still for the vascular and MRI measurements; 25 is the upper limit because the focus 
of the study is in on children and young adults) 
 
2) ADPKD diagnosis of ADPKD based on the presence of bilateral renal cysts when there is a positive family 
history 51 
 
3) Normal renal function with an estimated glomerular filtration rate (eGFR) >80 mL/min/1.73 m2 (using CKid 
Schwartz bedside equation for ages 6-17 52 and the CKD-EPI equation for ages 18-25 53) 
 
4) Ability to provide informed consent or assent 
 
 
Exclusion Criteria: 
 
 
1) Currently taking a curcumin supplement  
 
 
2) Current smoking or history of smoking in the past 12 months (rationale: changes in smoking habits during 
study involvement could confound the results) 102 
3)   Marijuana use within 2 weeks prior to FMDBA and aPWV testing (rationale: use may influence vascular 
function and cardiovascular changes, including blood pressure and heart rate) 
4)   Antioxidant and/or omega-3 fatty acid use within the past 4 weeks prior to FMDBA and aPWV testing and 
for the duration of the study (rationale: use may confound the effect of the acute ascorbic acid infusion on 
vascular function) 
5)   Alcohol dependence and abuse 
 
6) History of hospitalizations within the last 3 months 
 
7) Active infection or antibiotic therapy 
 
8) Pregnancy, lactation, or unwillingness to use adequate birth control.  All female participants of possible 
childbearing potential (Tanner Stage 2 or higher) will be required to take a pregnancy test at initiation of the 
study and then monthly during the study.  
 
9) Body-mass index >95th percentile using sex, age, and height for children 6-17 years of age, or > 40 kg/m2 
for young adults 18-25 years of age (rationale: vascular measurements can be inaccurate in severely 
obese patients).  The PI and co_I’s may use discretion to allow inclusion of children with body-mass index 
>95% if vascular measurements seem reasonable to perform.   
 
10) Inability to cooperate with or clinical contraindication for magnetic resonance imaging (MRI) including  
severe claustrophobia, implants, devices, or non-removable body piercings 
 
Special classes of subjects considered vulnerable populations will not be included in the study.  Dr. Chonchol 
will make final decisions on all patient eligibility.  
 


b) Sources of Research Materials.  This is a prospective study of newly recruited human subjects aged 6-25 
years with ADPKD.  The data collected will be used exclusively for research purposes.  All subject identities 
and records will remain strictly confidential. 
 
c) Potential Risks.  We see no psychological, social, or legal risks beyond those of participation in health-
related research in general.  The potential physical risks of participating in the proposed experiments are 
reasonably small.  The vascular measurements associated with Specific Aim 1 are completely non-invasive.  In 
children 6-17, the only invasive measurement with be collection of a small amount of blood.  All of the vascular 
procedures and the MRI scans have been used previously by the team of investigators in this patient 
population without complications.  Importantly, all of the procedures will be performed in University of Colorado 
Division of Renal Diseases and Hypertension Clinical Vascular Physiology Laboratory, a facility with on-site 
full-time supervision including nursing, safety equipment and established emergency procedures.  Moreover, 
the research will be overseen by a study-specific Data Safety Monitoring Board (DSMB) (described in more 
detail under Data and Safety Monitoring Plan). 
 
The risks associated with the experimental protocols include: 
Venous Catheter (ages 18-25 only) - Discomfort associated with insertion of the needle; local bleeding and 
a small hematoma (~10% of cases); risk of infection of a hematoma or significant external blood loss (<1 in 
1000), risk of fainting. 
 
Blood draw – Discomfort associated with the insertion of the needle; risk of bruising or feeling lightheaded 
or faint.  
 
Endothelium-Dependent Dilation (Brachial Artery Flow-Mediated Dilation [FMDBA]) - Inflating the blood 
pressure cuff during this procedure may cause a mild to moderate intensity “pins and needles or numbing” 
sensation that resolves when the cuff is deflated.     
 
Magnetic Resonance Imaging - The risk of performing abdominal MRI is minimal.  The magnetic field 
generated within the MRI is not harmful but can cause metal within the body to heat up or electronics to 
stop working.  All subjects will be questioned regarding the presence of metal or electronic devices inside 
their body.  All subjects with either metal implants or implanted electronic devices will be excluded from the 
study.  As the MRI tube is a small round tube, it may make subjects who experience claustrophobia 
uncomfortable, thus such individuals will be excluded.  The most common minor side effect of having an 
MRI exam is flashing lights in the eyes.  This is caused by the magnetic waves and is not harmful.  Some 
people also experience warmth and reddening of the skin, which usually goes away after a few minutes. 
For all female participants of possible childbearing potential, a negative pregnancy test prior to MRI will be 
required.  Severe claustrophobia is an exclusion criterion for the study.  Thus, undue stress due to a 
confined space during the MRI procedure will not be a potential risk.   
 
Medications/Dietary Supplements - With any medication used in testing, there is small risk of an allergic 
reaction.  Importantly, a physician will be available during the ascorbic acid infusion and nitroglycerin 
administration (ages 18-25 only) for assistance in the unlikely case of an adverse event.   
 
Reactions reported with the use of the specific medications proposed for use include:  
 
Curcumin - Curcumin is the active ingredient in the Indian spice turmeric and is generally 
recognized as safe (GRAS) by the FDA.  Detailed information about curcumin is found in the 
Research Strategy.  Few side-effects of curcumin have been reported with either 8-12 grams/day 
(8,000-12,000 milligrams/day) of short-term supplementation in adults 61,62,65 and children 64,66,67.  
The primary risk associated with curcumin supplementation is the possibility of temporary/transitory 
gastrointestinal distress (flatulence, constipation, diarrhea, nausea) in a very small percentage of 
individuals and with very high doses 61,65,67.  In the event that symptoms are intolerable, the dose 
will reduced from 25 mg/kg/day to 15 mg/kg/day.  Dr. Chonchol serves as a co-investigator on an 
ongoing NIH-funded trial using curcumin as a treatment of healthy aging (PI: Seals).  As a 
precaution, monthly negative home pregnancy tests will be required in all female participants of 
possible childbearing potential. 
 
Ascorbic Acid (ages 18-25 only) – Similar does of ascorbic acid has been infused intravenously 
without any unfavorable side effects in healthy subjects, as well as patients with chronic disease, 
including cardiovascular disease and chronic kidney disease 68,93,103,104.  However, administration of 
concentrated ascorbic acid may cause irritation to the local area around the infusion.  In order to 


reduce this risk we will dilute the infusion of ascorbic acid in sterile saline.  This procedure is 
currently safely employed in an NIH-funded, IRB-approved protocol in adults with ADPKD.    
 
Nitroglycerin (ages 18-25 only) - Nitroglycerin may cause a slight decrease in arterial blood 
pressure, minor symptoms such as lightheadedness, tingling in the tongue and in the arms and 
legs, headaches, fainting and/or increased heart rate.  The dose of nitroglycerin used is considered 
safe in the proposed population and is also used in patient populations to relieve angina 105.  This 
procedure is currently safely employed in an NIH-funded, IRB-approved protocol in adults with 
ADPKD.  Please see below for monitoring information.    
 
EMLA Cream (as needed) – EMLA cream may cause transient local skin reactions at the 
application site including paleness, erythema, and edema.  Uncommon side effects include a mild 
burning sensation, itching, or warmth at the application side.  In rare cases, allergic reactions or 
anaphylactic shock may occur.   
 
There are no alternative methods that would provide the same type and accuracy of information as the state-
of-the art procedures proposed in this application. 
 
2. Adequacy of Protection Against Risks 
 
a) Recruitment and Informed Consent.  I will use the recruitment and adherence strategies and experience 
previously implemented by myself and my mentorship team.  Dr. Chonchol has successfully recruited patients 
with different kidney diseases, including ADPKD, to clinical trials for many years.  Dr. Cadnapaphornchai has 
been performing research in children and young adults with ADPKD since 2001, including a recently completed 
3 year statin study in 110 children and young adults with ADPKD.  Patients for the study will be recruited from 
the ADPKD research center at the University of Colorado Denver Anschutz Medical Campus (UCD), with 
access to >4800 ADPKD patients around the country, including children and young adults.  Since 1985, UCD 
has maintained an ADPKD registry and mailing list.  Included in this registry are children and young adult 
ADPKD patients from the Denver Metro Area and all over the United States.  In addition to the UCD registry, I 
will advertise through the national PKD Foundation.  The ADPKD center at the UCD has longstanding 
expertise and national recognition, and therefore, is able to attract ADPKD patients from all over the United 
States for clinical studies.  Of note, UCD is currently the only group in the world performing research studies in 
children with ADPKD.  The feasibility of recruitment is supported by the recently completed intervention study 
performed by the co-mentor Dr. Cadnapaphornchai, which included 110 pediatric and young adult patients with 
ADPKD followed for a three-year period, including individuals out of state 56, and these participants will be 
recruited for the proposed research study.  The Division of Renal Diseases and Hypertension at the University 
of Colorado, in general, and Dr. Chonchol and Dr. Cadnapaphornchai specifically, have an excellent track 
record in recruiting participants and meeting enrollment goals for clinical trials.  Dr. Chonchol has served as PI 
or co-PI in many large multi-center clinical trials and will help monitor and guide the progress of the project. 
 
Written informed consent (participants ages 18-25 years of age and parent(s) of children 6-17 years of age) 
and assent (children 6-17 years) will be obtained using a standardized forms approved by the University of 
Colorado Multiple Institutional Review Board (IRB), that provides appropriate information about the study and 
the potential risks and benefits.  The parent(s) and/or child will read the consent/assent form and the 
investigator will review these forms and will answer any questions that the subject may have prior to obtaining 
the subject’s written consent/assent.  The consent form will then be signed by at least one parent and a 
witness for children under 18, or by the participant if 18-25 years of age, as well as by the investigator as 
documentation of consent.  The assent form will also be signed by children 6-17 years of age and by the 
investigator and a witness.  A copy of the signed consent/assent form(s) will be given to the subject/parent(s).  
All of the proposed procedures and protocols will be reviewed and approved by the University of Colorado 
Multiple IRB. 
 
Every attempt will be made to maintain patient’s confidentiality, although a potential risk is loss of 
confidentiality.  Since subjects participating in these studies have already been diagnosed with ADPKD, 
participation is unlikely to affect the ability of to obtain insurance.  The University of Colorado PKD research 
group has 30 years of experience recruiting patients with ADPKD, including patients from out of state.  The 
University of Colorado IRB is aware that our patients travel from out of state and we have taken precautions to 
ensure confidentiality when patients are traveling or getting blood drawn at a contract laboratory (Quest).   
 


b) Protection Against Risk. 
Minimizing General Risks - The potential general risks of the proposed studies will be minimized by: 
•  Screening for adverse events and allergies to drugs. 
• 
Using only safe, well-established procedures, with only qualified and experienced personnel performing the 
procedures. 
• 
Ensuring constant personal monitoring of each experimental session by the investigators and clinical staff. 
• 
Providing appropriate clinical supervision and emergency equipment through the Clinical Vascular 
Physiology Laboratory environment. 
•  Safety monitoring annually by a data safety monitoring board (DSMB). 
• 
Employing record keeping processes with complete confidentiality.  All subject identities and records will 
remain strictly confidential.  Individual subject data will not be associated with subject name. 
• 
Only performing the ascorbic acid infusion and sublingual nitroglycerin administration in a sub-set of young 
adult participants 18-25 years of age. 
• 
All blood pressure, blood draws and FMDBA measurements will be performed in the arm not designated for 
future vascular access for dialysis 
• 
A small venous catheter (for vitamin C intravenous infusion during FMDBA and aortic pulse-wave velocity 
measurements) will be placed in the arm or dorsal aspect of the hand (ages 18-25 only). 
 
Minimizing Specific Risks Related to Drugs/Supplements: 
• 
Risks to the subjects from curcumin administration will be minimized by using a dose and a duration of 
curcumin treatment that have been characterized repeatedly as safe and well tolerated in humans, 
including children 61,62,64,67.  In addition, scheduled safety checks (phone questionnaire) will occur after one 
month, three months, six months, and nine months of taking the curcumin (or placebo).  Serum creatinine, 
ALT and AST will be measured after one month, six months, and nine months, and for those out of state, 
will be performed at a local contracted laboratory (Quest).  Home pregnancy tests will be required monthly 
for all girls of possible childbearing potential (Tanner Stage 2 or higher).  All subjects will be given a digital 
blood pressure monitor (A&D Medical, UA767) with an appropriately sized cuff and the subject/parent will 
be instructed in its use.  Home blood pressures will be taken monthly and reported during phone safety 
checks.  This overall approach has been successfully employed previously by the co-mentor, Dr. 
Cadnapaphornchai 54,56.  In addition, potential side effects will be reviewed with participants at time of 
consent and subjects will be instructed to contact the study coordinator if they experience any side effects 
potentially associated with curcumin therapy. 
• 
Risks of local irritation from the use of ascorbic acid (ages 18-25 only) will be minimized by diluting the 
ascorbic acid in saline.   
• 
Risks associated with sublingual nitroglycerin (ages 18-25 only) will be minimized by screening out 
subjects who take vasodilating drugs that may interact with sublingual nitroglycerin (such subjects will still 
be eligible to participate in all other parts of the study), and not administering nitroglycerin to subjects with 
systolic blood pressure <100-mmHg, mean arterial pressure <70 mmHg, or history of migraines.  During 
nitroglycerin administration, heart rate and blood pressure will be monitored every 2 minutes for signs and 
symptoms of hypotension.  Additionally, an intravenous catheter (also used for ascorbic acid infusion) will 
be in place for administration of normal saline in the rare event of symptoms due to hypotension. 
• 
Risks associated with EMLA cream (as needed) – will be minimized by screening for hypersensitivity to 
prilocaine, lignocaine, or other local anesthetics of the amide type.   
 
Minimizing Specific Risks Related to Confidentiality:  
Strict confidentiality of patients’ information will be kept in accordance of HIPPA policy.  All clinical samples will 
be stored by code alone.  Data will be stored in Research Electronic Data Capture (RedCap), an encrypted, 
secured, HIPPA compliant website that meets all IRB regulations for secure data management.  Paper hard-
copies containing any identifiable information, will be locked in the research offices and in a locked cabinet, 
and will be accessible to members of the research team only on an as-needed basis.  The contract laboratory 
(Quest) will ensure strict confidentiality in accordance of HIPPA for all laboratory data.  All information in our 
database is treated with the same confidentiality as a medical record.         
 
3. Potential Benefits of the Proposed Research to the Subjects and Others 
Because the risks of participating in this study are relatively small, the risk-to-benefit ratio also is relatively low.  
Subjects will receive benefits associated with overall knowledge of their health from any testing performed.  


The results of the study have potential benefits for the treatment of vascular dysfunction in children and young 
adults with ADPKD, and possibly for slowing the progression of renal structural disease, which could potentially 
reduce overall cardiovascular and renal risk and mortality in this population. 
 
4. Importance of the Knowledge to be Gained 
 
The findings from the proposed research should provide important new information regarding the potential 
therapeutic effects of curcumin therapy on endothelial dysfunction and arterial stiffness in children and young 
adults with ADPKD, as there is no available information to date on these questions.  In addition, the proposed 
research should provide important insight into the mechanisms involved in any beneficial effects of curcumin 
on vascular function, as well as exploratory information regarding the influence of curcumin on total kidney 
volume.  Together, this information will contribute to future interventions to treat vascular dysfunction and 
reduce cardiovascular risk in this group of patients. 
 
5. Data Safety Monitoring Plan 
 
a) Medical Supervision and Subject Surveillance.  The trial will be performed by the University of Colorado 
Division of Renal Diseases and Hypertension research group located at the University of Colorado Anschutz 
Medical Campus.  The physicians, advanced practice providers, and nursing staff will have the responsibility of 
performing medical histories and physical examinations as part of the subject screening procedures.  The 
research nursing staff and trained phlebotomists perform the venous catheterizations (ages 18-25 only).  Dr. 
Michel Chonchol, a board certified nephrologist, will provide final decisions regarding subject 
screening/enrollment and will monitor/oversee clinical status and subject safety as they progress through the 
intervention. 
 
b) Data Safety Monitoring Plan.  A data safety monitoring board (DSMB) including clinicians (a nephrologist 
and pediatrician) and a statistician (independent of the study investigators but part of the faculty at the 
University of Colorado, School of Medicine) will be formed to assess potential adverse events.  These data will 
be prepared by the DSMB statistician, ensuring the study statistician remains blinded until the final analysis.  
The DSMB will meet annually to review the protocol and will follow the guidelines established by the NIH 
National Center for Research Resources which include: a) monitoring the progress of the protocol (e.g., 
reviewing subject recruitment, attrition and minority involvement) and the safety of research participants (e.g., 
reviewing unblinded data for safety); b) assuring compliance with requirements regarding the reporting of 
adverse events; c) assuring that any action that results in the temporary or permanent suspension of the 
protocol is reported to all the appropriate monitoring bodies (i.e., IRB, NIH, FDA, etc.); and d) assuring data 
accuracy and protocol compliance. 
 
c) Reporting of Side Effects.  Subjects will be instructed to report side effects to the investigator and their 
nephrologist, if not part of the investigative team.  Any serious adverse events will be reported to the Colorado 
Multiple IRB, Verdure Sciences, and the FDA, in accordance with the guidelines of each of these groups.  
Participants who drop out of the study will be handled using an intent-to-treat analysis. 
 
d) Exit Criteria.  The primary exit criteria will include completion of the study, , patient request, IRB or DSMB 
request, or other rationale as determined by the principal investigator or mentors.  Other exit criteria are listed 
below.  The number of subjects exiting the study and the reasons for exit will be carefully documented. 
 
Patient Stopping Criteria: 
•  Withdrawal of informed consent (subject’s decision to withdraw for any reason) 
•  Any clinical adverse event (AE), laboratory abnormality or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the subject 
•  Pregnancy 
•  Loss of ability to freely provide consent through imprisonment or involuntary incarceration for treatment of 
either a psychiatric or physical (e.g., infectious disease) illness 
•  Use of an investigational therapy or device other than study medication 
•  Significant non-compliance with protocol (i.e., procedures, assessments, medication, etc.) 
• Serious acute hypersensitivity reactions to investigational drug 
 
Study Stopping Criteria: 
The DSMB may recommend study stopping if: 
 The data show a significantly increased risk of serious adverse effects in the treatment group.   


 It becomes clear that successful completion of the study is not feasible (e.g. there is an excess of patient 
dropout, missing data, lack of recruitment etc). 
 
Clinical Trials.gov Requirements 
The application includes a trial which requires registration at ClinicalTrials.gov.  This registration will be 
performed. 
 
 
 
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MT, Cable NT, Green DJ. Does arterial shear explain the magnitude of flow-mediated dilation?: a 
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91. 
Jablonski KL, Decker E, Perrenoud L, Kendrick J, Chonchol M, Seals DR, Jalal D. Assessment of 
vascular function in patients with chronic kidney disease. J Vis Exp. 2014;16(88): doi: 10.3791/51478.  
PMID: 24962357 
92. 
Urbina EM, Williams RV, Alpert BS, Collins RT, Daniels SR, Hayman L, Jacobson M, Mahoney L, 
Mietus-Snyder M, Rocchini A, Steinberger J, McCrindle B. Noninvasive assessment of subclinical 
atherosclerosis in children and adolescents: recommendations for standard assessment for clinical 
research: a scientific statement from the American Heart Association. Hypertension. 2009;54(5):919-
950. 
93. 
Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, Vita JA, Levy D, Benjamin 
EJ. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation. 
2010;121(4):505-511. 
94. 
Jablonski KL, Seals DR, Eskurza I, Monahan KD, Donato AJ. High-dose ascorbic acid infusion 
abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men. J Appl 
Physiol. 2007;103(5):1715-1721. PMID: 17965239 
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Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, Salvetti A. Age-related reduction of 
NO availability and oxidative stress in humans. Hypertension. 2001;38(2):274-279. 


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Moreau KL, Gavin KM, Plum AE, Seals DR. Ascorbic acid selectively improves large elastic artery 
compliance in postmenopausal women. Hypertension. 2005;45(6):1107-1112. 
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Eskurza I, Monahan KD, Robinson JA, Seals DR. Ascorbic acid does not affect large elastic artery 
compliance or central blood pressure in young and older men. Am J Physiol Heart Circ Physiol. 
2004;286(4):H1528-1534. 
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free radical oxidation of arachidonic acid. J Am Soc Mass Spectrom. 1996;7(5):490-499. 
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Weimann A, Belling D, Poulsen HE. Measurement of 8-oxo-2'-deoxyguanosine and 8-oxo-2'-
deoxyadenosine in DNA and human urine by high performance liquid chromatography-electrospray 
tandem mass spectrometry. Free Radic Biol Med. 2001;30(7):757-764. 
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Donato AJ, Black AD, Jablonski KL, Gano LB, Seals DR. Aging is associated with greater nuclear N F 
kappa B, reduced I kappa B alpha, and increased expression of proinflammatory cytokines in vascular 
endothelial cells of healthy humans. Aging Cell. 2008;7(6):805-812. PMCID: PMC3032405 
101. 
Grantham JJ, Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King Jr. BF, Wetzel LH, 
Baumgarten, DA, Kenney PJ, Harris PC, Klahr S, Bennett WM, Hirschman GN, Meyers CM, Zhang X, 
Zhu F, Miller JP. Volume progression in polycystic kidney disease. N Engl J Med. 2006;354(20):2122-
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smoking and smoking cessation on endothelial function: 1-year outcomes from a randomized clinical 
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ICF_001.pdf: 
Informed Consent Form 
Project Title: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD  
NCT Number: NCT02494141 
Version Date: 03/12/2020 
Last Approval Date: 12/11/2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Consent and Authorization Form  
 
Page 1 of 14 
 
 
 
Principal Investigator: Kristen Nowak, Ph.D. 
COMIRB No: 15-0902 
 
Version Date: 3/12/2020  
 
 
Study Title: Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults 
with ADPKD 
 
You are being asked to be in a research study.  This form provides you with information about 
the study. A member of the research team will describe this study to you and answer all of your 
questions. Please read the information below and ask questions about anything you don’t 
understand before deciding whether or not to take part.  
 
Some people in this study may have a medical condition or a disability that does not allow them 
to make important decisions for themselves.  If you have been asked to decide for someone 
else whether they should be in this study, please read this consent form carefully.   
 
In this form, we use the words “you” and “your.”  If you are reading this form and deciding for 
someone else, the words ‘you’ and ‘your’ refer to that other person, not to you. 
 
Why is this study being done? 
This study plans to learn more about the effects of curcumin on blood vessel function in children 
and young adults with autosomal dominant polycystic kidney disease (ADPKD).  Curcumin in a 
dietary supplement and is a naturally occurring substance found in the Indian spice turmeric.  
Tumeric is commonly found in curry powder.  You are invited to participate in this research 
study to determine whether curcumin can improve the function of your blood vessels.   
 
Function of blood vessels is affected by how stiff they are and by a layer of cells called the 
endothelium.  In a healthy blood vessel, the endothelium helps blood vessels to become wider 
in response to triggers.   
  
In ADPKD, blood vessels do not function properly.  The blood vessels are stiffer and do not 
become as wide in response to triggers.  Patients with ADPKD often have increased 
inflammation and free radicals.  Increased inflammation and free radicals may be one reason 
why blood vessels do not work as well.   
 
You are being asked to participate in this research study to determine if curcumin will improve 
the function of your blood vessels.  We will also see if curcumin can slow the growth of your 
kidneys. 
You are being asked to participate in this research study because you are between 6-25 years 
of age and have ADPKD.  
Other people in this study 
 
Up to 68 children and young adults from your area will participate in the study.  
 
 


Consent and Authorization Form  
 
Page 1 of 14 
 
 
What happens if I join this study? 
Screening: 
Your first study visit is called the screening visit.  After signing this form, we will ask questions to 
determine if you qualify for the study.  We will review your medical history, medications, and lab 
work.  We may draw some blood from a vein in your arm if you do not have current lab work 
available.  You will also have a short physical exam.   
You will be asked to participate for approximately a 1 year period that will involve 7 visits 
(ranging from ½ hour to 3 hours [if you are under 18] or 5 hours per visit [if you are 18 or older]).  
Participation will take place in the research space of the Division of Renal Diseases and 
Hypertension Clinical Research Unit at the University of Colorado Anschutz Medical campus.  
The MRI scans will take place at the Brain Imaging Center on the University of Colorado 
Anschutz Medical campus.  Most visits will begin between 7 a.m. and 11 a.m.  
The treatment period may be extended by several months during extenuating circumstances 
limiting the ability to return the University of Colorado Anschutz Medical campus (e.g., COVID-
19 outbreak). 
You will be required to refrain from food (water is ok), exercise, non-prescription medications, 
and alcohol (if applicable) prior to some of the visits.  The study coordinator will review these 
restrictions with you. 
 If you live out of state, the lab work in the middle of the study will be arranged to occur 
elsewhere, and you will only need to come to the Anschutz Medical campus at the beginning 
and end of the study.   
Randomization: 
This study will have 2 different groups of research subjects like you.  To decide which group you 
will be in, we will use a method of chance.  This method is like flipping a coin or rolling dice. 
Each group will get slightly different care.  One group will receive curcumin and the other will 
receive a placebo.  A placebo is a pill or a liquid that looks like medicine but is not real.  It will 
have no medical effect on you.  In both groups, the drug or placebo will be given to you as a 
powder.   
 
You will not know which treatment group you are in.  Neither will your study doctor.  This 
information needs to be kept secret so that the study is based on scientific results, not on 
peoples’ opinions.  However, we can give this information out if you have an emergency. 
 
If you are in an emergency, make sure you tell the emergency staff about this study.  They can 
contact us, and we will give them all relevant information. 
 
Dosing of medication: 
If you are randomized to the study drug, you will take a dose that is specific to your body weight.  
The number of scoops of powder will differ depending on the person.  If you are in the placebo 


Consent and Authorization Form  
 
Page 1 of 14 
 
 
group you will still receive powder; but the powder will not have any medicine.  No matter what 
group you are in, we will have you measure the powder and mix it with food.  
 
 
Table of detailed visits: 
 
 
The table below illustrates the detailed visits if you enroll in the study. 
 
 
What are the possible benefits of the study? 
 
This study is designed for the researcher to learn more about the way blood vessels function in 
children with ADPKD. 
This study is not designed to treat any illness or to improve your health.  Also, there may be 
risks, as discussed in the section describing the discomforts or risks. 
 
Will I be paid for being in the study? 
 
You will be given a $10 gift card for your participation in the study.   
 
 
Will I have to pay for anything? 
 
It will not cost you anything to be in the study.   
 
 
Is my participation voluntary? 
 
Taking part in this study is voluntary.  You have the right to choose not to take part in this study.  
If you choose to take part, you have the right to stop at any time.  If you refuse or decide to 
withdraw later, you will not lose any benefits or rights to which you are entitled.  
 
 
Can I be removed from the study? 
 
The study investigator may decide to stop your participation without your permission if she 
thinks that being in the study may cause you harm, or for any other reason. 
 
 
Who do I call if I have questions? 
 
The researcher carrying out this study is Dr. Kristen Nowak.  You may ask any questions you 
have now.  If you have questions, concerns, or complaints later, you may call Dr. Nowak at 303-
724-4842.  
 
You will be given a copy of this form to keep. 
 
 
Visit 1 
(Screening)  
Visit 2  
(Baseline 
testing) 
Visit 3 
(Baseline 
testing ) 
Visit 4  
(Safety 
Check) 
Visit 5 
(Safety 
check, 
testing visit 
if local) 
Visit 6 
(End of 
study 
testing) 
Visit 7 
(End of 
study 
testing) 
Medical 
History  
         ×  
(may be 
completed 
at Visit 2) 
 ×  
(if not 
completed at 
Visit 1) 
  
  
 
 
 
Physical 
Examination 
×  
(may be 
completed  
at Visit 1) 
×  
(if not 
completed at 
Visit 1) 
 
 
 
× 
 
Blood Draw  
  × 
(may be 
completed  
at Visit 1) 
 × 
  
 × 
× 
× 
 
Blood 
pressure at 
rest 
× 
(may be 
completed  
at Visit 1) 
× 
 
 
× 
(only if you 
live in CO) 
× 
 
Urine 
Sample 
 
× 
 
 
 
× 
 
Blood Vessel 
Stiffness and 
Endothelial 
Function 
Tests 
 
 × 
 
  
× 
(only if you 
live in CO) 
× 
 
Saline and 
Vitamin C 
infusion 
 
× 
(only if you are 
18 or older) 
 
 
 
 
× 
(only if you 
are 18 or 
older) 
 
Nitroglycerin 
 
× 
(only if you are 
18 or older) 
 
 
 
 
× 
(only if you 
are 18 or 
older) 
 
MRI 
 
 
× 
 
 
 
× 
Receive 
study drug 
 
× 
 
 
 
 
 
 


Consent and Authorization Form  
 
Page 1 of 14 
 
 
You may have questions about your rights as someone in this study.  You can call Dr. Nowak 
with questions.  You can also call the responsible Institutional Review Board (COMIRB).  You 
can call them at 303-724-1055.  
 
 
Explanation of each session: 
 
Visit 1 (about 1 hr): 
 
Medical History and Physical Examination.  Your medical history and physical 
examination will be performed by a physician or nurse practitioner at the Division of 
Renal Diseases and Hypertension Clinical Research Unit.  You will also be asked about 
your family history of kidney disease, cardiovascular disease, diabetes, and cancer.  
Your body weight will be measured using a doctor’s office scale.   
 
Blood Draw.  A nurse or certified medical technician will place a small tube in a vein in 
your arm for drawing blood and will collect a blood sample (less than ½ a tablespoon) for 
markers of kidney and liver function.  
 
Pregnancy Test. If you are a female of possible child-bearing age, we will perform a 
pregnancy test even if you are sure you are not pregnant. 
 
Visit 2 (about 3 hours if under 18; about 5 hours if 18 or older): 
 
Medical History and Physical Examination.  (If not completed at Visit 1).  Your medical 
history and physical examination will be performed by a physician or nurse practitioner at 
the Division of Renal Diseases and Hypertension Clinical Research Unit.  You will also 
be asked about your family history of cardiovascular disease, diabetes, and cancer.  
Your body weight will be measured using a doctor’s office scale.   
 
 
Blood Pressure at Rest.  Your blood pressure will be measured as is done in your 
doctor’s office with a cuff on your upper arm. 
 
 
Blood Draw.  A nurse or certified medical technician will place a small tube in a vein in 
your arm for drawing blood and will collect a blood sample for markers of kidney and 
liver function (if not completed at Visit 1; less than ½ a tablespoon of blood), 
measurement of study drug levels (less than ½ a tablespoon of blood), measurements of 
markers of inflammation and free radicals (only if you are 18 or older; about 1 ½ 
tablespoons of blood), and immune cells (only if you are 18 or older; about 1 ½ 
tablespoons of blood).  If you sign the optional consent for future research, we will draw 
additional blood (about a tablespoon if you are 18 or older, less than ½ a tablespoon if 
you are under 18).    
 
 
Urine Sample.  We will collect a sample of urine to measure markers of free radicals.  
 
 
Blood Vessel Stiffness Test.  To test the “stiffness” of the walls of your arteries we will do 
two sets of measures.  First, a small probe will be placed flat on the surface of your skin 
at four sites and will record each time your heart beats.  The four sites are your carotid 
artery (side of neck), brachial artery (near the back of your elbow), femoral artery (upper 
leg/hip) and radial artery (wrist).  The faster your pulse moves between these sites, the 
stiffer your arteries are.  Second, an ultrasound will also be used on the surface of your 
skin to allow us to see how the size of an artery on the side of your neck (carotid artery) 
changes at rest.  This tells us how elastic (the opposite of stiffness) your artery is.   
 


Consent and Authorization Form  
 
Page 1 of 14 
 
 
 
Endothelial Function Test.  We will place an ultrasound probe on your skin over the 
major artery in your upper arm.  A small blood pressure cuff will be inflated tightly below 
your elbow cutting off the blood flow for 5 minutes.  The blood flow and size of your 
vessel will be measured before and after inflating the cuff.  This will allow us to measure 
your endothelial function (ability of blood vessels to dilate or get bigger).  You will also 
have electrodes on your chest to trace the electrical activity of your heart (ECG).   
 
 
Saline.  If you are 18 or older, we will infuse saline (water with salt) into an IV placed on 
the top of your hand for about an hour.  After 20 minutes of the infusion, we will make 
the measurements described above (Blood Vessel Stiffness Test and Endothelial 
Function Test). 
 
Vitamin C.  If you are 18 or older, we will then infuse vitamin C into the IV in your hand 
for about an hour.  After 20 minutes of the infusion, we will repeat the measurements of 
blood vessel function described above (Blood Vessel Stiffness Test and Endothelial 
Function Test).  
 
 
Nitroglycerin.  If you are 18 or older, a nitroglycerin pill will be placed under your tongue.  
Nitroglycerin is given to patients to relieve chest pain.  This pill will cause the major 
artery in your upper arm to increase in size.  We will look at your blood pressure and will 
collect ultrasound images of your blood vessel for 8 minutes after you take the 
nitroglycerin pill.  If your blood pressure decreases, we will make sure your blood 
pressure returns to where it started before we let you sit up. 
 
 
Receive Curcumin. A nurse will give you your first dose of the curcumin (or placebo) and 
the rest of the medication for you to take home to be use during the course of the study. 
 
 
Receive Blood Pressure Monitor.  A staff research coordinator will give you a blood 
pressure monitor and a chart to record blood pressure measurements.  The coordinator 
will review proper blood pressure measuring technique.  You will be asked to record your 
blood pressure once a month.   
 
 
Visit 3 (about 1 hour): 
 
MRI scan: You will have an MRI scan of your kidneys to measure the kidney size. 
 
Visit 4 (about 1 hour): 
 
Blood Draw.  A nurse or certified medical technician will place a small tube in a vein in 
your arm for drawing blood and will collect a blood sample for markers of kidney and 
liver function (less than ½ a tablespoon of blood) 
 
Visit 5 – If out you live out of state (about ½ hour): 
 
Blood Draw.  A nurse or certified medical technician will place a small tube in a vein in 
your arm for drawing blood and will collect a blood sample for markers of kidney and 
liver function (less than ½ a tablespoon of blood) 
 
Visit 5 – If you live local (about 1 ½ hours): 
 
Blood Draw.  A nurse or certified medical technician will place a small tube in a vein in 
your arm for drawing blood and will collect a blood sample for markers of kidney and 
liver function (less than ½ a tablespoon of blood) 
 


Consent and Authorization Form  
 
Page 1 of 14 
 
 
 
These tests will be performed as described above for Visit 2: 
o Blood Pressure at Rest 
o Blood Vessel Stiffness Test 
o Endothelial Function Test 
 
Visit 6 (about 2.5 hours if under 18; about 4.5 hours if 18 or older): The following tests will 
be done and are described above for visit 2: 
 
Physical Examination 
 
Blood Pressure at Rest 
 
Blood Draw 
o If you cannot return the University of Colorado at the 12 month time point, we will 
ask you to go to a locally contracted laboratory at this time for your clinical labs, 
and then remaining blood with be drawn at your end-of-study visit. 
 
Urine Sample 
 
Blood Vessel Stiffness Test 
 
Endothelial Function Test 
 
Saline Infusion (Only if 18 or older) 
 
Vitamin C Infusion (Only if 18 or older) 
 
Nitroglycerin (Only if 18 or older) 
 
Visit 7 (about 1 hour): 
 
MRI scan: You will have an MRI scan of your kidneys to measure the kidney size. 
 
Phone Safety Check. The coordinator will also call you after 1, 3, 6, and 9 months of taking the 
curcumin to check in with how you are doing and ask you some brief safety questions.   
What are the possible discomforts or risks? 
Discomforts you may experience while in this study include: 
1. Risks of having an MRI: In this study we will take an MRI of your kidneys.  The MRI machine 
uses powerful magnetic waves to take pictures inside the body.  The waves themselves are not 
harmful, but they can cause metal to heat up and electronics to stop working.   
You should NOT have an MRI if you have metal or electronic devices inside your body.   
Heart pacemakers and insulin pumps are examples of electronic devices. 
The MRI machine is a small round tube.  It might make you uncomfortable if you do not like tight 
spaces.   
The most common side effect of having an MRI is flashing lights in the eyes.  This is caused by 
the magnetic waves and is not harmful.  Some people also experience warmth and reddening of 
the skin.  This usually goes away after a few minutes.  
If you are pregnant, be sure to tell the person giving you the MRI. 
2. Risk of receiving curcumin or placebo:  Curcumin is a dietary supplement that is the active 
ingredient in the Indian spice turmeric.  It is designated as “generally recognized as safe” by the 


Consent and Authorization Form  
 
Page 1 of 14 
 
 
FDA.  Few side-effects of curcumin have been reported, and this primarily with higher doses 
than will be given in this study.  The primary risk is possible gastrointestinal distress (gas, 
constipation, diarrhea, or nausea) in a small percentage of people.  In the event that you 
develop symptoms that are not tolerable, we will reduce your dose of curcumin. 
 
3. Risks of Having Blood Taken: In this study we will need to collect about 1 ½ tablespoons or 
less of blood from you during each blood draw session.  During the entire study, a total of about 
2 tablespoons will be drawn if you are under 18, 7 ½ tablespoons if you are 18 or older, and an 
additional 1 or 2 (child/adult) tablespoons if you sign the optional consent for future research.  
We will get blood by putting a needle into one of your veins and letting the blood flow into a 
glass tube.   
 
Common side effects: You may feel some pain when the needle goes into your 
vein.  A day or two later, you may have a small bruise where the needle went 
under the skin.  
 
Rare side effects: There is also a small chance that you could feel lightheaded or 
faint during the blood draw.  
 
To make the blood draw easier, we may use a numbing cream on your skin 
before drawing blood.  
o Common side effects: The cream may cause temporary paleness, 
redness, or swelling to the skin where it is applied 
o Rare side effects:  There is an uncommon chance of mild burning, itching, 
or warmth of the skin.  Rarely, an allergic reaction may occur.  
Please let the investigator know if you have ever had a reaction to a skin numbing medicine. 
 
4. Risk of Endothelial Function Test:  
 
Common side effects: Inflating the blood pressure cuff just below your elbow 
during this test may cause a moderate intensity pain “pins and needles” or 
numbing sensation that goes away as soon as the cuff is deflated. 
 
5. Risk of receiving nitroglycerin under the tongue (Only done if 18 or older): Nitroglycerin is a drug 
used medically to treat chest pain.  
 
Common side effects: The most common reaction to this medication is a headache, 
which develops in approximately 60% of patients.  
 
Less common side effects: It can also cause a decrease in blood pressure, dizziness or 
lightheadedness. Placing the pill under your tongue may cause irritation in that area of 
your mouth. 
 
Rare side effects: In rare instances (1 in 1000) it may lower the heart rate, which could 
cause fainting.     
We will monitor your blood pressure and heart rate every 2 minutes during administration of 
nitroglycerin.  In addition, you will have an IV in place so fluids can be given if your blood 
pressure falls or fainting occurs. 
 
6. Risk of Having an IV Inserted in Your Vein (Only done if 18 or older): In this study, we will 
insert a needle, connected to a plastic tube, into a vein in your hand.  We will use the tube to 
give you fluids (hand).   


Consent and Authorization Form  
 
Page 1 of 14 
 
 
 
Common side effects: You will feel some pain when we first insert the tube into 
your vein. You may have some redness, swelling or bruising where the tube goes 
under your skin. 
 
Rare side effects: There is a small chance that you could feel lightheaded or faint 
during the IV insertion. In some cases, this type of tube can cause an infection 
where it goes under the skin, but the risk of infection is less than 1 in 1000.  In 
rare cases, it can cause a blood clot in the vein.  You will have the tube inserted 
in your hand for about 2 hours. 
 
7. Risk of Vitamin C Infusion (Only done if 18 or older) : 
 
Rare side effects: There is a chance the vitamin C may irritate your skin on your 
hand where it is being infused, but this uncommon because we dilute (water-
down) the vitamin C in saline (water with salt).   
 
8. Risks if pregnant or become pregnant:  If you become pregnant, the particular treatment or 
procedures involved in the study may involve risks to the embryo or fetus which are currently 
unclear. You may not be in the study if you are breastfeeding, pregnant, or plan to become 
pregnant during the study.  If you are a female who is old enough to potentially become 
pregnant, you will need to take a pregnancy test prior to receiving the study medication and 
monthly while in the study.  If you become pregnant during the course of the study, you must 
stop taking your study medication right away, and contact your doctor or study staff. 
 
There is a risk that people outside of the research team will see your research information.  We 
will do all that we can to protect your information, but it cannot be guaranteed. 
 
The study may include risks that are unknown at this time. 
What are the possible benefits of the study? 
This study is designed for the researcher to learn more about the effects of curcumin on blood 
vessel function and kidney growth in children and young adults with ADPKD.  However, there is 
no guarantee that your health will improve if you join this study.  Also, there could be risks to 
being in this study.  If there are risks, these are described in the section describing the 
discomforts or risks. 
 
Are there alternative treatments? 
 
There may be other ways of treating ADPKD.  These other ways include lowering blood 
pressure if it is elevated.  These treatments will be continued throughout the period of the study 
if you are already receiving them, and may be started at the beginning of the study period if you 
are not. 
 
You should talk to your doctor about your choices.  Make sure you understand all of your 
choices before you decide to take part in this study.  You may leave this study and still have 
these other choices available to you.  
 
Who is paying for this study?  
 
The research is being paid for by the National Institutes of Health.   


Consent and Authorization Form  
 
Page 1 of 14 
 
 
Will I be paid for being in the study?   
You will not be paid to be in the study.  Travel and hotel reimbursement may be offered if you do 
not live in the greater Denver metropolitan area.  
Will I have to pay for anything? 
It will not cost you anything to be in the study.   
Is my participation voluntary? 
Taking part in this study is voluntary.  You have the right to choose not to take part in this study.   
If you choose to take part, you have the right to stop at any time.  If you refuse or decide to 
withdraw later, you will not lose any benefits or rights to which you are entitled.   
 
If you decide to leave the study early, you will be asked to make one final visit so that you can 
complete the testing planned for the final visit.   
 
If there are any new findings during the study that may affect whether you want to continue to 
take part, you will be told about them. 
Can I be removed from this study?  
You may be taken out of the study if the study doctor thinks it is not safe for you to be in the 
study.  You can be taken out of the study even if you do not want to leave the study.  Also, the 
sponsor can decide to stop the study at any time. 
What happens if I am injured or hurt during the study? 
If you have an injury while you are in this study, you should call Dr. Nowak immediately.  Her 
phone number is 303-724-4842.  We will arrange to get you medical care if you have an injury 
that is caused by this research.  However, you or your insurance company will have to pay for 
that care. 
Who do I call if I have questions? 
The researcher carrying out this study is Dr. Kristen Nowak. You may ask any questions you 
have now. If you have questions, concerns, or complaints later, you may call Dr. Nowak at 303-
724-4842. You will be given a copy of this form to keep.   
 
You may have questions about your rights as someone in this study. You can call Dr. Nowak 
with questions.  You can also call the responsible Institutional Review Board (COMIRB).  You 
can call them at 303-724-1055.  
 
A description of this clinical trial will be available on http://www.Clinical Trials.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. 
 
Optional Consent for Blood and Urine Banking for Future Research 
 
Dr. Kristen Nowak would like to keep some of the blood and urine that are taken during the 
study but is not used for other tests.  If you agree, we will keep some of the blood and urine 
already taken in the study and also take an additional tablespoon of blood if you are 18 or older 
and less than half a tablespoon of additional blood if you are under 18.  If you agree, the blood 


Consent and Authorization Form  
 
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and urine will be kept and may be used in future research to learn more about chronic kidney 
disease and autosomal dominant polycystic kidney disease.  The research that is done with 
your blood and urine is not designed to specifically help you.  It might help people who have 
chronic kidney disease and autosomal dominant polycystic kidney disease and other diseases 
in the future.  Reports about research done with your blood and urine will not be given to you or 
your doctor. These reports will not be put in your health records.  The research using your blood 
and urine will not affect your care. 
 
The choice to let Dr. Kristen Nowak keep the blood and urine for future research is up to you. 
No matter what you decide to do, it will not affect the care that you will receive as part of the 
study.  If you decide now that your blood and urine can be kept for research, you can change 
your mind at any time and contact your study doctor to let him or her know that you do not want 
Dr. Kristen Nowak to use your blood and urine any longer, and they will no longer be used for 
research.  Otherwise, they may be kept until they are used up, or until Dr. Kristen Nowak 
decides to destroy them.  
When your blood and urine are given to other researchers in the future Dr. Kristen Nowak will 
not give them your name, address, phone number or any other information that will let the 
researchers know who you are.  
 
Sometimes blood and urine are used for genetic research (about diseases that are passed on in 
families).  Even if your blood and urine are used for this kind of research, the results will not be 
told to you and will not be put in your health records.  Your blood and urine will only be used for 
research and will not be sold.  The research done with your blood and urine may help to 
develop new products in the future, but there is no plan for you to be paid. 
 
The possible benefits of research from your blood and urine include learning more about what 
causes chronic kidney disease, autosomal dominant polycystic kidney disease, and other 
diseases, how to prevent them and how to treat them.  The greatest risk to you is the release of 
your private information.  Dr. Kristen Nowak will protect your records so that your name, 
address and phone number will be kept private.  The chance that this information will be given 
to someone else is very small.  There will be no cost to you for any data or sample collection 
and storage by Dr. Kristen Nowak. 
 
Please read each sentence below and think about your choice. After reading each sentence, 
circle “yes” or “no.”  If you have questions, please talk to your doctor or nurse.  Remember, no 
matter what you decide to do about the storage and future use of your blood and urine, you may 
still take part in the study. 
 
I give my permission for my blood and urine to be stored in a central tissue bank at the 
University of Colorado for future use by the study investigators: 
 
1. I give my permissions for my blood and urine to be kept by Dr. Kristen Nowak for use 
in future research to learn more about how to prevent, detect, or treat autosomal 
dominant polycystic kidney disease. 
 
   Yes 
 
   No 
_________Initials 
 
2. I give my permissions for my blood and urine to be used for research about other 
health problems (for example: causes of heart disease, osteoporosis, diabetes). 
 


Consent and Authorization Form  
 
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   Yes 
 
   No 
_________Initials 
 
3. I give my permission for the University of Colorado Division of Renal Diseases and 
Hypertension to contact me in the future to ask me to take part in more research. 
 
                      
   Yes 
 
   No 
_________Initials 
 
Who will see my research information? 
 
The University of Colorado Denver (UCD) and its affiliated hospital(s) have rules to protect 
information about you.  Federal and state laws including the Health Insurance Portability and 
Accountability Act (HIPAA) also protect your privacy.  This part of the consent form tells you 
what information about you may be collected in this study and who might see or use it.   
The institutions involved in this study include:  
 
 University of Colorado Denver 
 Children’s Hospital Colorado (CHCO) 
 University of Colorado Hospital 
 
CHCO shares a medical record system with the Barbara Davis Center and PedsConnect; 
therefore it is also possible that your information could be viewed by healthcare professionals at 
these organizations. 
 
We cannot do this study without your permission to see, use and give out your information.  You 
do not have to give us this permission.  If you do not, then you may not join this study.   
 
We will see, use and disclose your information only as described in this form and in our Notice 
of Privacy Practices; however, people outside the UCD and its affiliate hospitals may not be 
covered by this obligation. 
 
We will do everything we can to maintain the confidentiality of your personal information but 
confidentiality cannot be guaranteed.  
 
The use and disclosure of your information has no time limit.  You can cancel your permission to 
use and disclose your information at any time by writing to the study’s Principal Investigator (PI), 
at the name and address listed below.  If you do cancel your permission to use and disclose 
your information, your part in this study will end and no further information about you will be 
collected.  Your cancellation would not affect information already collected in this study.   
 
 
 
Dr. Kristen Nowak 
 
 
Division of Renal Diseases and Hypertension 
 
 
 
12700 East 19th Avenue, C281 
 
 
Aurora, CO  80045 
 
 
303-724-4842 
 
Both the research records that identify you and the consent form signed by you may be looked 
at by others who have a legal right to see that information, such as:   


Consent and Authorization Form  
 
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 
Federal offices such as the Food and Drug Administration (FDA) and the Office of Human 
Research Protections (OHRP) that protect research subjects like you. 
 
People at the Colorado Multiple Institutional Review Board (COMIRB) 
 
The study doctor and the rest of the study team. 
 
The National Institutes of Health, who is the company paying for this research study. 
 
Officials at the institution where the research is conducted and officials at other institutions 
involved in this study who are in charge of making sure that we follow all of the rules for 
research 
We might talk about this research study at meetings.  We might also print the results of this 
research study in relevant journals.  But we will always keep the names of the research 
subjects, like you, private.  
 
You have the right to request access to your personal health information from the Investigator. 
To ensure proper evaluation of test results, your access to these study results may not be 
allowed until after the study is completed. 
 
Information about you that will be seen, collected, used and disclosed in this study: 
 Name and Demographic Information (age, sex, ethnicity, address, phone number, 
etc.) 
 Portions of my previous and current Medical Records that are relevant to this study, 
including but not limited to Diagnosis(es), History and Physical, laboratory studies, 
radiology studies, procedure results 
   Research Visit and Research Test records 
 
What happens to Data, Blood and Specimens that are collected in this study?  
 
Scientists at the University of Colorado Denver and the hospitals involved in this study work 
to find the causes and cures of disease.  The data, blood and specimens collected from you 
during this study are important to this study and to future research.  If you join this study: 
 
 
The data, tissue, blood, or other specimens given by you to the investigators for this 
research no longer belong to you.   
 
Both the investigators and any sponsor of this research may study your data, blood, or 
other specimens collected from you. 
 
If data, blood, or other specimens are in a form that identifies you, UCD or the hospitals 
involved in this study may use them for future research only with your consent or 
Institutional Review Board (IRB) approval. 
 
Any product or idea created by the researchers working on this study will not belong to 
you. 
 
There is no plan for you to receive any financial benefit from the creation, use or sale of 
such a product or idea.  
  
HIPAA Authorization for Optional Additional Study Procedures  
 


Consent and Authorization Form  
 
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In this form, you were given the option to agree to additional, optional research procedures.  
You must also give us your permission, under HIPAA rules, to use and disclose the 
information collected from these optional procedures, as described above.   
 
If you decline to give us permission to use and disclose your information, you cannot take 
part in these optional procedures, but you can still participate in the main study.  Please 
initial next to your choice: 
_____ I give permission for my information, from the optional procedures I have agreed to 
above, to be used and disclosed as described in this section. 
 
_____ I do not give permission for my information for any optional procedures to be used 
and disclosed; I understand that I will not participate in any optional procedures. 
 
Certificate of Confidentiality 
This study has been issued a Certificate of Confidentiality from the federal government to 
help protect your privacy. The Certificate prohibits the researchers from disclosing your 
name, or any identifiable information, document or biospecimen from the research, with the 
exceptions listed below. A certificate provides protections against disclosing research 
information in federal, state, or local civil, criminal, administrative, legislative or other 
proceedings. 
These protections apply only to your research records. The protections do not apply to your 
medical records.  
The researchers may disclose your name or identifiable information, document or 
biospecimen, under the following circumstances: 
 
To those connected with the research, 
 
If required by Federal, State or local laws, 
 
If necessary for your medical treatment, with your consent, 
 
For other scientific research conducted in compliance with Federal regulations, 
 
To comply with mandated reporting, such as a possible threat to harm yourself or others, 
reports of child abuse, and required communicable disease reporting, or 
 
Under other circumstances with your consent. 
A Certificate of Confidentiality does not protect information you or a member of your family 
voluntarily release. 


Consent and Authorization Form  
 
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Agreement to be in this study and use my data 
I have read this paper about the study or it was read to me.  I understand the possible risks and 
benefits of this study.  I understand and authorize the access, use and disclosure of my 
information as stated in this form.  I know that being in this study is voluntary.  I choose to be in 
this study: I will get a signed and dated copy of this consent form. 
 
 
Signature: 
 
 
 
 
 
 
 
 
Date___________ 
Print Name: 
 
 
 
 
 
 
 
 
Signature: 
 
 
 
 
 
 
 
 
Date___________ 
 
Print Name: 
 
 
 
 
 
 
 
 
___________________________________________  Date_________ 
Child (13-17 year olds) 
 
 
 
Witness Signature_________________________________________ Date_________ 
 
 
Print Name: 
 
 
 
 
 
 
 
 
 
Witness of Signature  
 
 
Witness of consent process  
Consent form explained by: ______________________________  
Date___________ 
 
Print Name ___________________________________________