Clinical trial NCT04505410
Conditions: Ulcerative Colitis
Sponsor: University of Miami
Start date: 2020-09-18; Completion date: 2023-12-07
Enrollment: 32 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether a diet intervention (the Fasting Mimicking diet) will help induce clinical and biochemical response to an advanced therapy in patients with ulcerative colitis. Study period will be 8 weeks during induction of advanced therapies. The primary aims of this study will be clinical response, as determined by the simple clinical colitis activity index (SCCAI). Secondary outcomes will be improvement in fecal calprotectin and C-reactive protein levels.

Detailed description:
Advanced therapies included will be:

JAK inhibitors (tofacitinib or upadacitinib) IL-23 inhibitors (ustekinumab or risankizumab) Anti-TNF (infliximab)

Patients will be provided these medications as part of their standard of care, as decided by their treating physician.

Arms: arm 1: Participants in this group with UC consuming a standard, regular low-fiber diet will start an advanced therapy for eight consecutive weeks with the addition of two, five-day cycles of Fast Mimicking Diet (FMD) daily meals on weeks 2 and 7. arm 2: Participants in this group with UC consuming a diet based on tolerance will start an advanced therapy for eight consecutive weeks.
Interventions: intervention 1: A plant based high fiber diet that mimics fasting ("FMD") plus advanced therapy intervention 2: Advanced therapy only without dietary intervention
Intervention descriptions: intervention 1: Patients will do two 5-day cycles of a fasting mimicking diet. They will start the first diet cycle 1 week after initiating a new advanced therapy: Tofacitinib and Upadacitinib (JAK inhibitors), Infliximab (anti-TNF), Ustekinumab or Risankizumab (IL-23 inhibitors). intervention 2: Patients in this group will start an advanced therapy and follow a diet solely based on dietary tolerance: new advanced therapy: Tofacitinib and Upadacitinib (JAK inhibitors), Infliximab (anti-TNF), Ustekinumab or Risankizumab (IL-23 inhibitors).

Protocol documents:
Prot_SAP_000.pdf: 
 
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A randomized control study to examine the influence of a healthy diet on moderate to severe 
ulcerative colitis patients undergoing tofacitinib induction 
 
 
 
National Clinical Trial (NCT) identified Number: NCT04505410 
 
 
 
Principal Investigator: Oriana M. Damas, MD MSCTI 
 
 
 
Sponsor: University of Miami Miller School of Medicine 
 
 
 
Funded by: Pfizer (PI-initiated Study) 
 
 
 
Version Number: 3, 10/05/2021 
 
 
 
 
IRB Study Number: 20200436 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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1) 
Protocol Title 
A randomized control study to examine the influence of a healthy diet on moderate to severe 
ulcerative colitis patients undergoing tofacitinib induction 
 
2) 
Objectives* 
The overarching goal is to use fasting mimicking diet (FMD) as adjunctive treatment for UC patients 
undergoing induction with biological medications (tofacitinib, anti-TNFs, ustekinumab or 
vedolizumab), and to identify microbiome and metabolome changes occurring as a result of the diet + 
biologic medication intervention. This will provide the foundation for predicting response to therapy. 
The objectives of this study are 1) to determine if a FMD dietary intervention improves clinical 
response to biologic medication 8-week induction therapy in UC 2) to identify predictors of clinical 
response to biologic medications in the baseline dietary pattern and 3) to identify changes in the stool 
microbiome and metabolome that could predict response. The study population will include adult 
participants with moderate to severe ulcerative colitis who are starting tofacitinib or other biologic 
medications at our University of Miami Crohn’s and Colitis Center. 
 
3) 
Background* 
Ulcerative colitis (UC) is a chronic disease that can lead to devastating consequences including 
colectomy 1. Medical therapy has improved significantly but there are still many patients with poor 
response to therapy 1. For example, in OCTAVE induction trials 1 and 2, approximately 59.9% of 
patients had clinical response to tofacitinib but this still left 40.1% who did not show any 
improvement by week 8 2. With that as a backdrop, diet offers a safe opportunity to complement 
immune-based therapy in sick UC patients. The effect of diet may be only on symptoms but may also 
be on inflammation. To date, there is only one published study that has looked at the impact of diet on 
reducing symptoms of an active UC flare-up 3. This small study was focused on reducing symptoms 
not inflammation 4. Additionally, there are no studies in UC that have proposed to combine diet and 
medical therapy to improve clinical response. A study in Crohn’s disease looked at a plant-based diet 
as adjunctive therapy to infliximab and found that 96% achieved clinical remission by week 6 
compared to published remission rates of 64% using monotherapy alone 5,6. This study demonstrates 
the potential of using diet as a safe adjunctive therapy to biologics and lays the foundation for this 
proposal. We propose to evaluate the effect of the fasting mimicking diet (FMD) on clinical response. 
We will use this diet because of its reported efficacy in reducing colonic inflammation, improving 
intestinal regeneration, and expansion of beneficial bacteria like Lactobacillacea and 
Bifidobacteriacea.12 
A great deal of research has been devoted to identifying genetic and microbial factors underpinning 
IBD. In spite of the investments made in this type of research, we still have not been able to develop 
actionable strategies based on this knowledge. In particular, diet has the possibility of changing the 
microbiome and metabolome to reduce the signs and symptoms of UC. Our group has recently 
completed a small but comprehensive study in UC patients in remission and found that a low fat, high 
fiber diet can improve quality of life and lower serum levels of inflammatory markers. But no one has 
specifically performed a prospective, controlled study of diet in the context of a sick UC patient and 
paired with an effective drug. Moreover, little is known about the effects of dietary + drug manipulation 
on the human microbiota and metabolome. Therefore, this study seeks to determine whether intervals 
of FMD will enhance response to biologic therapy by week 8 in a randomized, diet placebo-controlled 


 
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trial. We will measure baseline diet patterns and evaluate whether a change in diet influences clinical 
response. By measuring the baseline microbiome in the stool and again after the last FMD interval, we 
will be able to measure changes occurring as a result of diet intervention. We will use tofacitinib and 
available FDA approved biologic therapies available for the treatment of UC (anti-TNFs, vedolizumab 
and ustekinumab) to examine the impact of diet on UC clinical response. Embedded within this 
proposal are the seeds of future studies that will test dietary interventions incorporating predictive 
factors we will identify in this proposal. 
 
Innovation. Our project is novel for the followed reasons: 
● A proper, randomized controlled study of a protocolized dietary intervention in active 
ulcerative colitis has not been done. This will potentially eliminate the confounders introduced 
by uncontrolled, under-powered, diet study designs available. 
● Our study will include patients who have active moderate to severe UC since these types of 
patients are typically excluded from dietary studies but are actually the ones that need the most 
help. 
● The fasting mimicking diet (FMD) is a novel dietary approach. Animal and human studies 
demonstrate efficacy in reducing colonic inflammation. 
● Microbiome or metabolome changes have not been studied in active UC using diet as treatment. 
These microbiome changes may identify mechanisms by which diet may be helpful. 
 
This study builds upon prior existing work done including diet studies performed at our institution. 
Below we describe existing evidence and our own pilot data that explain the background for this 
proposal. 
Preliminary data 
Existing Evidence 
Diet can influence ongoing inflammation in UC. There are multiple studies demonstrating that a 
“western diet” characterized by a diet high in animal protein, processed foods, and low in fiber from 
fruits and vegetables, is associated with a greater risk of developing inflammatory bowel disease 
(IBD).8, 9,10 Recent studies suggest that a diet that in turn “prudent diets”, low in Western dietary 
components, may in turn help reduce colonic inflammation.8 Beyond epidemiologic data, we have a 
greater understanding of the role that diet may play in prevention of relapse in IBD. However, most 
studies however have focused on diets that may help in Crohn’s disease but not in UC.9 There is also 
a lack of randomized controlled studies with protocolized diets that will measure the effects of diet on 
inflammation and who seek to understand mechanisms of response. Most studies of diet in UC are 
biased by small sample sizes, uncontrolled methods and there are no well designed studies aiming to 
decrease active inflammation in UC. 
 
Fasting Mimicking Diet (FMD) is a novel diet that may help attenuate inflammation in UC. The 
fasting mimicking diet, is a novel low calorie diet that is characterized by episodes of intermittent 
“fake” fasting, that has the potential to work in attenuating inflammation in UC.12 Prior studies 
demonstrate that calorie restriction can improve aging, dementia, metabolic syndrome, obesity and 
diabetes. 11 Intermittent fasting elicits an adaptive cellular response that improves glucose regulation, 
increases stress resistance, and suppresses inflammation 11. During intermittent fasting there is 
activation of cellular pathways that enhance intrinsic defenses against oxidative and metabolic stress 


 
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and those that remove and repair damaged molecules 11. Pertinent to UC, cells respond to intermittent 
fasting by engaging in a coordinated adaptive stress response that leads to increased expression of 
antioxidant defenses, DNA repair, and autophagy, and down- regulation of inflammation. There is a 
clear association between a dysregulated autophagy pathway and development of IBD, providing a 
mechanism by which this diet may help in IBD. Further, following a fasting period, cells then engage 
in tissue specific processes of growth and plasticity that can bolster healing 12. 
The FMD allows participants to consume meals and snacks while at the same time maintaining 
the properties that mimic fasting and elicit similar cellular responses. Prior studies using the FMD 
have examined 5 days of “fasting” with intervals of 25 days in between each fasting12. The diet is 
low in carbs and protein yet high in healthy fats such as olives and flax. fats. All meals and snacks are 
whole-food derived and plant based. Day one of the diet provides ~1,090 kcal (10% protein, 56% fat, 
34% carbs), while days two through five provide only 725 kcal (9% protein, 44% fat, 47% carbs), 
designed to provide ~54% of normal caloric intake. A recently published study examined the effects 
of this fasting diet in animal models of colitis and in an uncontrolled study of 26 humans12. In murine 
models of colitis, intervals of the FMD reduced intestinal inflammation and CRP, promoted intestinal 
regeneration and stimulated growth of protective gut populations such as Lactobacillacea and 
Bidifidobacteriacea.12 In the human sample of UC patients, FMD was safe, feasible and effective in 
reducing systemic inflammation (measured as total white blood cell count and lymphocytes).12 These 
studies highlight a sensible mechanism by which intermittent fasting may help reduce colitis 
including via resetting of the autophagy pathways. The FMD is an improvement of the intermittent 
(water) fasting diet that may help inflammation while limiting weight loss and improving patient 
tolerability. 
 
The microbiome and diet-induced metabolites are a critical link between diet and intestinal 
inflammation in UC and may permit the development of biomarkers of response. Diet is a major 
driver of the intestinal microbiome 13,14 and downstream metabolites and as mentioned it also plays a 
critical role in the pathogenesis of UC 13-16. Multiple studies have shown that there is a dramatic 
decrease in bacterial diversity in patients with UC, especially in bacteria known to produce short chain 
fatty acids (SCFA)17- 20, which have anti-inflammatory properties 17,21,22. When healthy humans were 
placed on an animal-based diet, rich in fat and protein, there was a rapid decrease in abundance of 
SCFA-generating bacteria like Roseburia 16 and an increase in Bacteroides 23, which can induce colitis 
in genetically susceptible mice 24. Animal based diets are also associated with increases in 
Enterobacteriaceae including Escherichia, associated with inflammation in IBD patients 25. Changes in 
the UC gut microbiome are associated with changes in the gut metabolome 26. These data suggest that 
the microbiome/metabolome transduces many aspects of diet as treatment for UC. It also suggests 
that specific microbial/metabolic signatures may be useful to predict responses to specific diets. 
Preliminary data from our Crohn’s and Colitis Center: 
A low fat diet (LFD) improves QoL and systemic inflammation in patients with UC. We have 
performed a pilot study of a LFD versus HFD intervention in UC patients that were in remission to 
mildly active. The study was a randomized, parallel-group, cross- over study of two 4-week periods 
with each participant serving as her/his own control. We have completed 18 UC patients who received 
a catered, LFD or a HFD. We targeted patients with inactive or only mildly active disease. The HFD 
arm was based on NHANES data where 35-40% of the calories are from fat with a 20-30:1 ratio of 
omega-6/omega-3 fatty acids with less than 12 g of fiber per day. In the LFD arm, 10% of calories 
are from fat, with an approximate ratio of 1:1 of omega-6/omega-3 fatty acids with 25-35 g fiber per 


 
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day which is the USDA recommended amount for women and men. The adherence to the diet 
intervention using the patients self-reported data as entered in Nutrihand is quite high and matches the 
preset goals. In our preliminary data, we have demonstrated a significant improvement in quality of 
life (short IBD questionnaire) after a low fat/high fiber diet (p=0.03), and lowered serum amyloid 
levels, a marker of mucosal healing. These data justify using a low saturated fat diet such as the 
Fasting Mimicking Diet in UC to decrease clinical symptoms, improve QoL, and decrease 
inflammation. 
A controlled diet intervention with a low fat diet (LFD) in UC leads to changes in the microbiome 
and metabolome. Our laboratory is well-versed in studies involving the intestinal 
microbiome/metabolome in humans and animal models. Preliminary analysis of the microbiome in 18 
patients who completed a pilot diet study demonstrate there is no statistical significant change at 
beta/alpha diversity in the microbiome after the LFD. However, we found a significant difference at 
the phylum level. In LFD, Actinobacteria (p=0.02) decreased while Bacteroidetes (p=0.05) increased 
(Figure 3). Furthermore, at the genus level there was a decrease in Bifidobacterium (p=0.04); 
Collinsella (p=0.03); Coprococcus (p=0.05) and an increase in Prevotella (p=0.008) and Blautia 
(p=0.016) (data not shown). We also found significant microbiome changes at Beta diversity between 
patients that started a LFD compared to patients that started first on HFD (data not shown). For the 
metabolome, we used a targeted and an untargeted analysis of stool. We have validated our 
preliminary untargeted metabolomics of 44 fecal samples (11 patients at 4 time points) data with 
PLS-DA (Partial Least Squares discriminant analysis) model to determine the metabolomic 
differences between the diets. Our preliminary data revealed striking changes of metabolites between 
Baseline and LFD (Figure 4). Additionally, based on VIP score (>1), we have identified a few 
putative compounds from the untargeted approach at baseline (i.e. Lauric acid and Dopaquinone) 
which are normally high in UC and CD27. After LFD, these 2 metabolites were decreased but omega- 3 
fatty acids were increased, which is known to reduce inflammation27. Together these data not only 
demonstrate that we are capable of performing microbiome/metabolomics experiments, but it also 
provides justification to pursue the identification and role of dietary metabolites in response to a diet 
low in saturated fats, such as the FMD. 
4) 
Inclusion and Exclusion Criteria* 
Inclusion: We will include adult patients with a confirmed diagnosis of UC living in South 
Florida, a population that is ethnically diverse. Patients to be included will have moderate to 
severely acting UC, defined as active disease on the SCCAI (>2), with presence of rectal 
bleeding 
Exclusions: The presence of clinical findings suggestive of Crohn’s disease, clinical signs of 
fulminant colitis, toxic megacolon, or indeterminate, microscopic, ischemic, or infectious colitis or 
impending hospitalization for severe ulcerative colitis.. Other exclusion criteria include: patients with 
allergies to nuts/soy/sesame/oats/celery or celeriac, patients that are diabetic on a glucose lowering 
drug, individuals with a history of syncope/presyncope with fasting or from medical conditions, 
women who are pregnant or nursing, individuals with very low BMI<18 and patients, and patients 
with the following comorbidities: chronic kidney disease, diabetes, active cancer. Permitted 
concomitant medications for ulcerative colitis will be oral aminosalicylates and oral glucocorticoids. 
Given the study population includes a sick cohort with active symptoms, we will need to permit the 
use of oral corticosteroids as many patients biologic medications will be on them. Because of the 
anticipated variability in the consumption of oral steroids, we will take prednisone dose into account 


 
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in our multivariable logistic regression model (using dose as a continuous covariate which will allow 
us to factor in differences in dosage). Prohibited concomitant therapies will include azathioprine, 
methotrexate, and mercaptopurine. Additionally, patients with a history of routinely fasting, patients 
who do not like the food items that form part of the kits for the fasting mimicking diet or patients 
with dietary restrictions. Patients with a fever, cough, respiratory distress or other symptoms of an 
active infection.  Patients who are adults but unable to consent, minors, pregnant women and 
prisoners are excluded from participation.  
  
5) 
Number of Subjects* 
In this study we will include a total of 76 patients (38 per arm). This medium-sized study will 
be essential to lay the groundwork to add diet into the IBD treatment algorithm. 
 
6) 
Study-Wide Recruitment Methods* 
This study will recruit patients from the University of Miami Center for Crohn’s and Colitis 
and from Gastro Health, a large medical, private-practice group located in Kendall, Florida.   
Gastro Health is made up of board-certified physicians and allied health professionals 
specializing in the treatment of gastrointestinal disorders, nutrition and digestive health.  
Gastro Health physicians are involved in clinical research and medical education and 
currently collaborate with the Division of Gastroenterology on multiple research studies 
involving IBD. Thus, adding this FMD study would be an ideal and seamless process.   
 
7) 
Recruitment Methods 
The University of Miami Center for Crohn’s and Colitis serves 5,000 patients with IBD from 
which to recruit ethnically-diverse study participants. Our prior experience with conducting 
diet studies is evidenced in the preliminary data. Participants will be recruited during routine 
primary care visits, using physician-centered recruitment at the Crohn’s and Colitis Center at 
the University of Miami and at Gastro Health. To promote interest in physician-centered 
recruitment, we will educate the physicians at the University of Miami Center for Crohn’s and 
Colitis and at Gastro Health about the study’s aims and procedures prior to the study’s start.  
We will ensure that information will be available to facilitate physician referrals. Physicians 
from both sites will be able to initiate a referral for any interested patient who they feel may 
benefit from involvement. We are also going to use flyers so that patients may contact us.  
For their participation in this study participants will be compensated a total of $60 in monetary gift 
cards. The participant may choose to receive a $30 gift card after completing visit 1, this includes 
initial baseline questionnaires, blood draw and stool kit and a second $30 gift card after completing 
Visit 2 (week 7), this includes food diaries, follow-up questionnaires, and a second set of blood draw 
and stool kit.  They may also choose to receive the full $60 altogether after completing both study 
visits.  If a participant withdraws from the study, they may only be compensated for any study visit 
completed.  
 
Additionally, if participants are starting tofacitnib therapy participants will receive the tofacitinib pills 
for a total of 8 weeks. This will not be processed through their insurance and will not require 


 
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authorization. However, participants will be advised that authorization of their insurance will be 
required for tofacitinib after 8 weeks. If participants are starting any other biologic medication 
therapy this will be processed through their insurance.  
 
Valet parking tickets will also be validated each time the subject visits the clinic for study-related 
visits. 
 
 
8) 
Study Timelines* 
Seventy-six patients will be enrolled at different time points throughout this study in groups of 
approximately ten. Each patient will be an active participant in the study for a total of 8 
weeks. A complete breakdown of the study timeline is provided below:  
Milestones and Timeline (1-3 months) 
IRB: Protocol/Consent review. IRB approval within 1-2 months. *We had a similar pilot 
diet study we do not anticipate delay 
Order fasting mimicking diet kits for the first set up of patients --1 month to receive 
Creation of RedCap database to manage clinical data and biospecimens 
Set up randomization 
Research coordinator will be trained by dietician on diet methods for initial recruitment 
and follow up. 
Milestones (3-6 months) 
Enroll 10 participants using a 1:1 randomization strategy 
Follow up visits of enrolled participants 
Inflammatory markers preparation of collected samples 
Genomic DNA preparation of collected samples 
Milestones (6-12 months) 
Re-evaluation of study methods, compliance of fasting intervals and adjustments if 
needed. 
Reorder fasting mimicking kits for next set of patients 
Enroll next 10 participants using a 1:1 randomization strategy 
Follow up visits of enrolled participants 
Inflammatory markers preparation of collected samples 


 
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genomic DNA preparation of collected samples 
Preliminary analyses and evaluation of results for possible presentation at national 
conferences 
Milestones (12-15 months) 
Enroll next 20 participants using a 1:1 randomization 
Follow up visits of enrolled participants 
Inflammatory markers preparation of collected samples 
Genomic DNA preparation of collected samples 
Milestones (16 months-24 months) 
Reordering of FMD kits 
Enroll next 20 participants using a 1:1 randomization 
Follow up visits of enrolled participants 
Inflammatory markers preparation of collected samples 
genomic DNA preparation of collected samples 
Milestones (2 years-2.5 yrs) 
Enroll last 18 participants using a 1:1 randomization 
Follow up visits of enrolled participants 
Inflammatory markers preparation of collected samples 
genomic DNA preparation of collected samples 
Begin to gather preliminary analyses, meet with biostatisticians, submit abstracts to 
large national conferences. 
Milestones (2.6 yrs-3 years) 
Shipment of samples 
Biostatistical analysis 
Interpretation of results and manuscript preparation (planned submission to 
Gastroenterology journal). 


 
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9) 
Study Endpoints* 
On the premise of the existing literature and our own preliminary data, we propose a fasting 
mimicking diet as a non-pharmacological treatment for patients with active moderate to severe UC to 
augment clinical response to biologic medication induction therapy. Our application further aims to 
identify baseline dietary patterns and microbiome factors that predict enhanced response to a fasting 
mimicking diet as adjunctive therapy to biologic medication induction. 
 
Aim 1. To determine whether a fasting mimicking diet used as adjunctive therapy during 
biologic induction enhances response to therapy in patients with moderate to severe UC. 
Questions to be answered: 
1. 
Does consumption of two 5-day intervals of a FMD improve clinical response to 
tofacitinib or other biologic medications (Anti-TNFs, vedolizumab, ustekinumab)by week 
8 compared to medications alone? 
2. 
Does performing two 5-day intervals of a FMD improve biochemical markers of 
inflammation by week 8 compared to tofacitinib or other biologic medications alone? 
Rationale: We poorly understand which diet is most effective at attenuating colonic inflammation 
in UC. At present, patients who are actively flaring are advised to adhere to a low fiber diet to 
minimize symptoms; but this diet has no role in reducing inflammation and is associated with 
microbial dysbiosis in the long term28. Prior studies show that the FMD decreases colonic 
inflammation, stimulates intestinal regeneration, and promotes growth of healthy intestinal bacteria 
like Lactobacilli that can in turn regulate T cell activity and reduce the severity of IBD symptoms 
29. We therefore hypothesize that patients who adhere to two cycles of a FMD within the 8 week 
induction period of biologic medications are more likely to have a clinical response than patients 
who follow a standard (low fiber diet) and biologic medicationtherapy by week 8. 
Health Outcomes: The primary end-point will be clinical response at 8 weeks. Clinical response 
will be assessed using the simple clinical colitis activity index (SCCAI), a validated measure of 
disease activity in UC (see ref). The SCCAI questionnaire will be completed by the physician, 
based on interview and examination of the patient. Variables assessed include bowel frequency (day 
and night), urgency, blood in stool, general well- being and presence of extra-intestinal 
manifestations. A higher SCCAI indicates greater disease activity (range of 0-19), and a clinical 
response is defined as a SCCAI decrease of ≥2 points from baseline. Secondary outcomes will be: 
clinical remission, defined as a SCCAI of ≤ 2 by week 8, steroid-free clinical response and 
remission, and improvement of biochemical markers including CRP and stool fecal calprotectin. 
 
Co-variates collected: We will collect baseline body weight, age, and disease severity and again at 
8 weeks. At baseline we will collect gender, ethnicity and race, as well as a prior history of their 
disease (location of disease and disease severity included). Any co- variate determined to influence 
disease activity or baseline diet will be accounted for in multivariable regression models.  
 
Aim 2. To determine whether baseline dietary patterns influence clinical response to a fasting 
mimicking diet intervention. 
Questions to be answered: 
A. Does a baseline dietary pattern high in Western dietary components predict 


 
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response to FMD intervention? 
B. Are there non-Western diet patterns that predict response FMD intervention?  
 
Rationale: There are no studies examining whether baseline diet influences response to therapy in IBD. 
The diet of patients with UC varies widely based on diet tolerance and often has poor nutritional value, 
including higher consumption of refined carbohydrates that are characteristic of Western dietary 
patterns 35. Prior studies show that diet patterns capture a more sensitive global assessment of diet than 
individual food groups or macro/micronutrients alone 35. A Western dietary pattern is a diet high in 
processed foods, animal protein, and low in fruits/vegetables previously associated with IBD onset 
(ref). We hypothesize that those who score high in a Western dietary pattern score and then undergo 
FMD intervals will likely have the most clinical response compared to those who score lower in the 
Western pattern score and undergo a FMD intervention. 
Expected Outcomes/Results: We anticipate that a baseline diet pattern that is consistent with a high 
Western dietary score will likely result in more significant improvement in clinical symptoms than 
those whose baseline diet pattern is lower in the Western diet score. In other words, an “unhealthier” 
diet at baseline, will result in the most improvement of symptoms after a change in diet to the FMD 
intervention. This is under the premise that if patients score low in a Western diet pattern, they are 
more likely to consume healthy foods, and therefore less likely to benefit from a diet intervention 
study. 
Aim 3. To dissect the effects of a fasting mimicking diet intervention on the microbiome and 
the metabolome in UC. 
Questions to be answered: 
A. What is the effect of a FMD on the fecal microbiome composition and 
metabolome? 
B.  What are possible predictors of response to tofacitinib or other biologic medication therapy 
plus FMD in the microbiome composition? 
 
Aim 3A- Examine microbiome and metabolome changes in UC patients in response to FMD plus 
biologic medication vsbiologic medication . Diet may improve clinical response to biologic 
therapies by changing the microbiome. Previous studies have not adequately evaluated the impact of 
a protocolized diet on active UC inflammation. We know that dietary modification can rapidly 
change the human gut microbiome, making it likely that diet-based approaches can sustain a healthy 
microbiota which may be a more beneficial approach to long term UC management39,40,41. Human 
studies have not addressed the effects of the FMD on the microbiome and metabolome in UC. We 
hypothesize that the FMD plus biologic medications will improve dysbiosis by changing bacterial 
diversity and relative abundance of major bacterial groups compared to the patients’ baseline and 
compared to patients receiving biologic medications alone. We further hypothesize that these 
changes will affect the production of bioactive metabolites.  
 
Exploratory Aim 3B. To identify patterns in the microbiome and metabolome that could 
predict clinical response to the FMD in combination with biologic medications. Our study is not 
powered to detect predictors of response to therapy but this exploratory aim will be a hypothesis 
generating experiment to determine if we identify microbiome/metabolome changes that could be 
used as predictors of response to FMD+ biologic medications A prior study examining microbiome 
predictors of response to vedolizumab found that there was a higher abundance of butyrate 


 
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producers at baseline in therapy-responsive CD patients44. Therefore, we hypothesize that there 
will be baseline differences in the abundance and diversity of the microbiome composition and also 
in metabolites produced between those who respond to FMD intervention compared to those who 
do not respond. Results from this preliminary analysis will be used to design future large validation 
cohorts. 
 
Anticipated outcomes and future directions Aim 3a and 3b: We predict we will see an increase 
in alpha-diversity in patients receiving FMD plus biologic medications compared to biologic 
medications alone. We also expect an increase in diversity, and a shift to increase Bacteriodetes over 
Firmicutes as was seen in the initial FMD studies in healthy participants 12. Based on prior studies, 
we expect to find a higher abundance of butyrate producers at baseline in therapy-responsive UC 
patients. In the future, we want to drill down to whether a particular microbiome predicts clinical 
response of a patient with UC to FMD. To that end, future studies will use stool from patients with 
clinical/biochemical benefit to FMD versus those that have not had a benefit to “humanize” germ-
free mice. Humanizing germ-free mice with microbiota from patients has been used to better 
understand the functional aspects of the microbiota that sequencing analyses do not provide 45,46 Our 
investigative team has experience with these studies and we do not expect any technical issues. 
.  
 
10) Procedures Involved* 
We will evaluate the effect on clinical response of adding two FMD intervals into standard biologic 
medication induction. Eligible participants (see inclusion criteria) will be randomly assigned to 
either Arm 1 (2 intervals of FMD + biologic medication at standard dose of induction) or Arm 2 of 
the study (standard low fiber dietary recommendations + biologic medication at standard dose of 
induction); Figure 1. Both arms will have initial baseline assessments including a detailed IBD 
questionnaire querying disease activity and severity, as well as a “short” IBD Quality of Life 
questionnaire. Baseline serum CRP and stool for measurement of fecal calprotectin, microbiome and 
metabolites to be repeated again in both arms 2 days after completion of the last FMD interval (week 
7, Thursday). Additionally, we will measure levels of ketosis in participants of the FMD arm for 
indications of fasting. If not possible we will arrange with a local lab to collect samples and send 
them with an overnight currier. We will perform the second sample collection 2 days after finishing 
the last FMD based on prior methods evaluating microbiome changes from the FMD 29. A last 
assessment of clinical response, IBD questionnaires,  and medication updates will be performed at the 
end of the week 8 induction period. Randomization: We will perform randomization using a random 
allocation sequence that will be prepared online (www.stattrek.com), a statistical and analytical tool 
that uses block randomization with a 1:1 ratio of FMD to standard low fiber diet. Participants will be 
blinded to the diet allocation and informed that both diets could change the amount of protein, 
carbohydrates and fat intake from their regular diet and restrict caloric intake for max 5 days but that 
one diet is under investigation and the other is a standard diet provided to patients.  
Figure 1. see below, next page 


 
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Instruments for diet ascertainment: We will use the three following validated diet questionnaires:  
1. The National Health and Nutrition Examination Survey (NHANES) Food Frequency Questionnaire 
(FFQ). The FFQ will be self-administered but guidance will be provided if needed by our staff 
nutritionist. Nutritional calculations will be performed by uploading the questionnaire results through 
the NCI website with diet* Calc v1.5.0.30. The study dietician will assist with these calculations and 
interpretation. We will measure baseline diet on all enrolled patients using a validated food-frequency 
questionnaire (FFQ) to measure diet intake over the last year. Participants will be asked to complete 
FFQ at baseline.  
 
2. Automated Self Administered-24 (ASA-24) is a validated nutritional questionnaire that queries 
food intake over the last 24 hour period.31 The ASA24 will be self-administered but guidance will be 
provided if needed by our staff nutritionist.  Participants will be asked to complete an ASA24 recall at 
baseline, between week 4 and 5, and a third time at week 8 (end of study). 
 
3. NutriHand® is a web-based food diary online tool. Their services allow planning, tracking, 
analyzing and reporting on meals and medical information. Only participants in the FMD arm will be 
required to enter their daily food intake and only during the fasting mimicking diet weeks, 2 and 5. 
NutriHand® will be self-administered but guidance will be provided if needed by our staff 
nutritionist.   
 
The Fasting Mimicking Diet: FMD and low fiber diet advice will be provided to all participants by 
the same research dietician with extensive training in IBD counseling before the start of the 
intervention and will last approximately 20 minutes. In order to standardize and ensure appropriate 
intake of the FMD, we will purchase commercially available kits of the FMD and provide them to 
patients one week before each planned interval (at study recruitment and again at week 5, just prior to 


 
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initiation of the second FMD at week 6) (Fig 1) 32. The kits will be purchased through L-Nutra , their 
Prolon® 5-day meal plan include foods such as soups, snacks, bards, teas and supplements (omega-3 
fatty acids) for a total of 66 items per box. The diet is plant-based, gluten free and dairy free without 
any artificial preservatives, chemicals or biologically active ingredients. Participants in the FMD arm 
will also be provided with a “Tips and Tricks” pamphlet for additional nutritional guidance. Patients 
will be instructed to maintain water intake constant in both arms, to 8 glasses a day. On Day 6, after 
the FMD, users will be instructed to avoid binge eating and resume their normal diet gradually. They 
should start with liquid foods, such as soups and fruit juices, followed by light meals, including rice, 
pasta and small portions of meat, fish and/or legumes. A normal diet can be resumed on day 7, or 24 
hours after the FMD interval as per protocol from prior FMD studies 33. To monitor adherence, 
participants will be instructed to record everyday all the food they eat in a food diary (NutriHand®) or 
take pictures of their food and email them to a secure email address. The email address will be 
created solely for the purpose of this study through the University of Miami Information Technology 
Department and will be registered under the Univeristy's secure server. The dietician will monitor the 
NutriHand® provider website and the email inbox daily to ensure foods are being recorded, if food is 
not recorded, the dietician takes immediate action and calls the patient.  
 
11) Data and Specimen Banking* 
During the course of the clinical interventions in Aim 1, we will collect serum and stool (baseline and 
week 7) to microbiome/metabolome changes (Figure 1). Patients in the study will collect a morning 
stool sample and bring it to the clinic on ice, or an arranged FexEx shipping method. This stool will be 
aliquoted in an anaerobic chamber as to not disturb the anaerobic flora, snap frozen, and stored at -
80OC the same day until analysis of microbiome/metabolome changes. Storage will be done at the 
Abreu lab (see LOS). We have chosen to perform metagenomic shotgun sequencing of stool to 
identify specific microbes and also abundance of microbial genes including microbial enzymes. This 
will provide insight into the microbiota beyond the superficial description of bacterial community 
structure using 16S sequencing. Furthermore, we will pair metagenomic sequencing with 
metabolomic profiling to identify host-microbial interaction and downstream actionable targets. 
Total genomic DNA will be isolated from one frozen aliquot using QIAamp DNA Stool Mini Kit 
(Qiagen) in Dr. Abreu’s laboratory. Genomic DNA will then be sent to the University of Minnesota 
Genomics Core Facility for microbiome metagenomic sequencing. From the raw sequencing data, Dr. 
Ban from the BCC Core will utilize curated genome databases and a high-performance data-mining 
algorithm that rapidly disambiguates hundreds of millions of metagenomic sequence reads into the 
discrete microorganisms engendering the particular sequences. Overall classification precision is 
maintained through aggregation statistics. The last aliquot will be sent to the Proteomics & 
Metabolomics Facility at the Wistar Institute for metabolomics analyses. We routinely use these 2 
facilities for all our microbiome sequencing and metabolomics analyses. Briefly, polar metabolites 
are separated under HILIC pH 9 condition and analyzed using a Thermo Q-Exactive HFX mass 
spectrometer 42. Metabolites identification and quantification will be performed using Compound 
Discoverer 3.0 from a list of more than 200 verified compounds. Additionally, MS/MS data 
fragmentation and database will be searched against the mzCloud library (mzcloud.org) for potential 
identification and quantification of metabolites with a minimum score of 50,70,71. The raw data set 
will be transformed into principal components (PC), such as principal component analysis (PCA), 
orthogonal partial least square discriminant analysis (OPLS-DA), or partial least square- discriminant 
analysis (PLS-DA) 43 


 
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12) Data Management* 
  
Power analysis: Given the lack of data on the influence of diet on induction of remission in UC, we 
used a diet study that measured the effect of diet on clinical remission in CD patients undergoing 
infliximab induction to conduct power analysis. Similar to the FMD, this diet was plant-based. The 
study reports that 96% of patients who followed the diet intervention in combination with infliximab 
had clinical remission compared to reported rates of clinical remission using IFX alone (64%) 33. We 
calculate based on this study that approximately 76 patients in each arm (38 patients assigned to 
receive tofacitinib or other biologic medication plus FMD and 38 patients assigned to receive 
tofacitinib or other biologic medication only) would provide the trials with 80% power to detect a 
difference of 32 percentage points between the tofacitinib or other biologic medication + diet group 
and the tofacitinib or other biologic medication only group in the rates of the primary end points, 
assuming rates in the control arm of 64% for the primary end point. This would allow us to detect an 
alpha significance of 5%. 
Aim 1 Analysis: All subjects will be included in the arm assigned regardless of treatment adherence 
(intention to treat). We will compare the percentage of patients who achieved clinical response among 
participants in Arm 1 to those in Arm 2 after 8 weeks, taking into account clinically significant 
covariates using multivariable logistic regression. We will also compare SCCAI as a continuous end 
point using multivariable linear regression. Secondary outcomes including improvement in fecal 
calprotectin and CRP will be evaluated as continuous outcomes, using multivariable linear regression, 
taking into account relevant covariates. Clinical categorical will be analyzed using chi-square or 
Fisher’s Exact Test. Continuous variables will be analyzed using student’s t-tests, ANOVA or Mann-
Whitney U tests depending on their distribution. Statistical analyses will be performed using R studio. 
Aim 2 Analysis: Prior studies derive a Western diet pattern using subset of 40 food groups. 9,36,37 
This is done by factor analysis done to aggregate food groups based on degree of correlation between 
the food item and data set. We will conduct a confirmatory factor analysis (CFA) on the WD 
indicators and will compute factor scores for each patient using previously calculated factor 
loadings.36,37 A dietary pattern score is  generated  for  each participant  by  summing  weighted  
intakes  of  food  groups,  adjusted  for  energy consumption  using  the  residual  method.9,36,37  
After construction of Western diet pattern scores for each patient, we will examine the association 
between scores and the clinical response, measured as a categorical and continuous variable (using 
SCCAI score, described in Aim 1). We will examine the effect of diet pattern (continuous) on clinical 
response (categorical) using multivariable logistic regression on each diet score, taking into account 
covariates mentioned in Aim 1. 
Aim 3a/3b: Plan of analysis of microbiome and metabolite data: Our metabolomic data will be 
complemented with our microbiome and metadata, such as clinical parameters (change in SCCAI, 
fecal calprotectin, CRP) and diet to extrapolate a mechanistic model that will explain the 
microbial/metabolite community structure and function. Dr. Ban from our BCCC core, has 
collaborated with us on these types of data analyses from another similar study (publication pending). 
This integrative method for exploring such data is necessary to advance the understanding of the 
microbial metabolites and the microbial community. We will use this mechanistic model to examine 
which bacteria produce the metabolites but also which specific inflammatory markers (CRP/Fecal 
calprotectin) and clinical data link to this production. Using this computational analytical approach, 
we further hypothesize that we will see trends in clinical parameters which will allow us to correlate 
it to environmental cues in the human gut, such as microbiome and metabolites. To assess the 


 
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differences between the clinical parameters and clinical response, we will use permutational 
multivariate analysis of variance. Therefore, different parameters will be addressed in each 
experimental setup, and full permutation of the data will be done with Monte–Carlo tests (accounting 
for type III error), where the fixed effects sum to zero with 9,999 permutations. For the first 
experiment, the factors will be the SCCAI score and the presence/absence of clinical parameters. For 
the second test, the factors are each microbiome, metabolites and clinical parameters. For all the 
experiments, statistical comparisons will be performed using one-way ANOVA (Tukey’s test) to 
compare pairwise differences between treatments. 
13) Provisions to Monitor the Data to Ensure the Safety of Subjects* 
All data will be safeguarded in accordance with the Health Insurance Portability and 
Accountability Act (HIPAA) and the principles and practices of strict confidentiality. The 
interview and survey responses from formative evaluation will not be linked to identifying 
information. Data will be stored in a locked file cabinet and files will be stored on a password 
protected computer in a password protected database in the office of the PI. Participants will 
be provided a unique identifier to be used in data analysis. Last, no individuals will be 
identified in any presentations or publications resulting from this research. In such a way we 
are protecting participants from risks related to privacy and confidentiality. 
 
14) Withdrawal of Subjects* 
Participation in this research study is voluntary. Participants can choose not to participate in 
this study either at the beginning or at any time during the study. There is no penalty nor any 
loss of benefits for participants. Participants will be compensated for completed study visits. 
Withdrawing will not have an adverse impact on participant’s present or future health care. 
For their safety, participants will be asked to undergo a final evaluation visit. Participants can 
contact dietitian or study coordinator if they wish to withdraw from study. 
Participants may be withdrawn from study without their consent if they are not able to follow 
dietary recommendations or if the participant does not tolerate biologic medication  therapy. 
These cases will be carefully reviewed by the participant’s physician.  
All the information about the participant and the samples (blood, urine, saliva, or other samples) we 
obtain will be kept. This data will remain as part of the study database. Participants will also be asked 
if we can continue to review their medical record and collect data about their medical care in the 
future.  If they agree to allow us to keep collecting data after withdrawing from the study, this new 
data will be handled the same as the other research data.  
 
15) Risks to Subjects* 
Certain risks are associated with the participation in the study: 
Participants may not like the particular dietary guidance given to them and they may not find dietary 
recommendations to their liking. Participants may also experience more hunger, mainly if their usual, 
baseline diet is higher in calories than the study diet. 
 
The process of interviewing may cause distress and discomfort because will be talking about personal 
activities and thoughts. It is possible that some of the questions that are asked are similar or the same 


 
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as others asked by other health professionals and the participant may wonder why it is necessary to 
answer them again.  It may be tiresome to you to be asked these questions again. 
The investigator will also make a judgment about the ability to understand this consent form and the 
ability to participate in the interview. 
 
In addition, patient may experience discomfort or fatigue in having the study doctors ask questions on 
the phone, in person, and with the questionnaires.  The risks of answering questions are minimal, but 
the participant can stop at any point if the participant feel too tired to continue with the assessments. 
 
The risks of blood drawing include: fainting, temporary pain, and/or bruising at the site of the needle 
stick.  Rarely, infection or the formation of a small clot or swelling of the vein and surrounding area 
may occur. Although the samples used for the current study are coded, there is still a minimal risk of 
confidentiality breach. However, all the clinical and phenotypic data that can be linked to the samples 
is saved in UM password-protected databases and only authorized personnel can access them. 
 
16) Potential Benefits to Subjects* 
Subjects may not benefit directly from participating in this study, although it is possible that they 
experience improvement in their medical symptoms if the diet intervention is effective. However, this 
benefit may decrease or end once participation in the study ends and if they choose to go back to eating 
their regular diet.   
 
17) Vulnerable Populations* 
N/A, This research does not involve vulnerable populations. 
18) Multi-Site Research* 
This is not a multi-site study.  
 
19) Community-Based Participatory Research* 
This is not a community-based participatory research study  
 
20) Sharing of Results with Subjects* 
 
Most tests done on samples in this research study are only for research and have no clear meaning for 
a participant’s health care.  However, if the research with identifiable information or samples gives 
results that do have meaning for a participant’s health, the researchers will contact the participant.  
 
21) Setting 
Recruitment for this study will take place at the following location:  
• The Crohn’s & Colitis Center/UMHC University of Miami Hospital & Clinics  


 
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 Located on the +first floor +at 1475 N.W. 12th Avenue, Miami, Florida, 33136. 
Sylvester and UMHC are in connecting buildings on the northeast corner of the N.W. 
12th Avenue and N.W. 14th Street intersection. 
Phone: 305-243-UMGI (8644) option 3, option 4 
Fax: 305-689-1852 
22) Resources Available 
Principal Investigator - Oriana M. Damas, M.D., 
Dr. Damas is Assistant Professor of Medicine and the Director of Translational Studies at the 
University of Miami. Dr. Damas has experience in translational studies and diet in 
inflammatory bowel disease (IBD). Her research focuses on the influence of diet and genetics 
on predictors of disease relapse in ulcerative colitis patients, ultimately with the hope of 
identifying patient-profile panels that will identify/predict what they will respond to. She will 
be in charge of the recruitment of patients and will be responsible for the overall project 
design, supervision, data analyses and generation of project reports and publications. Her 
mentor, Maria T. Abreu, will continue to be available to her for ideas, problem-solving, 
logistics and for grant writing/publications. 
Clinical Research Coordinator 
A CRC with preferably 2 years of experience as a Clinical Research Coordinator. Preferably trained 
in ascertainment protocols, procedures, and data management. Will help recruit patients for ongoing 
diet study. Will work closely with Dr. Damas in approaches to tracking adherence and maintaining 
high rates of follow-up. Will be responsible for regulatory and compliance application and 
maintenance. Will also assist with RedCap data entry during the length of the study.  
 
Dietician  
A dietitian with preferably 2 years of clinical and research experience.   The dietician will preferably 
have extensive experience in diet education, Medical Nutrition Therapy and evaluation of nutritional 
outcome. In addition, experience on healthy lifestyle intervention programs and nutrition counseling 
software is preferred. The dietician is in charge of the nutritional assessment and description of the 
diets before and during diet intervention of the recruited patients. Dietician’s bulk effort in years 1-3 
will be dedicated to ensuring patients are adhering to dietary interventions (total of 10 days per 
patient) and that patients maintain a low residue diet in the control arm. The dietician will also 
oversee daily food diary monitoring during FMD intervals and corrective action necessary to 
maintain adherence to the diet. 
 
Bioinformatician (10% effort, year 3) 
A bioinformatician with preferably a PhD in computational science and statistics and experience. The 
bioinformatician will focus on the statistical associations between all the data collected during this 
proposal.  
 
23) Prior Approvals 
N/A 


 
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24) Local Number of Subjects 
76 subjects will be enrolled in this study in order to complete the research procedures.    
The total number eligible subjects to be screened is unknown.  
 
25) Confidentiality 
Check all that apply:  
 
 
  Data obtained or created for this research will be stored on an encrypted 
electronic device or system owned by the University of Miami or on a cloud 
storage system that has been approved by the University of Miami for storage 
or research data.  
 
 The Investigator (or research staff) will record (e.g. write down, abstract) 
data collected in a manner that does not include any indirect or direct 
identifiers and the recorded data will not be linked to the individual’s’ 
identity.   
 
 The investigator (or research staff) will record (e.g. write down, abstract) 
the data collected in a manner that does not include any direct identifiers of the 
subject. The investigator will assign a code to each subject and link the code 
to the subject’s identity.  The research team will maintain the link to the 
subject’s identity on a document separate from the research data.  Both 
documents will be stored in separate files on a University of Miami encrypted 
device or on a University of Miami approved cloud storage system. The 
research team will destroy the identifiers at the earliest opportunity. 
 
 The research team will maintain the research data for at least three years.  
 
  Bio-Specimens obtained for this research will be stored without any direct 
or indirect identifiers.   
 
 
 Bio-Specimens obtained for this research will be stored in a de-identified 
coded manner.   
  When required to transport data or bio-specimens for this research, the 
research team will transport the data and bio-specimens in a de-identified (or 
anonymous) manner with a link to the individual subject’s identity maintain 
separately from the data and/or bio-specimen. 
26) Provisions to Protect the Privacy Interests of Subjects 
The research team will inform participants that optimum measures will be taken to limit the use or 
disclosure of their personal information, including information from this research study and from their 
medical records, to people who have a need to review this information.  


 
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Subjects will also be informed of the following privacy protection provisions that will be made: 
  
• We will remove identifiable information from data we collect  
• After we remove all of the identifiers, we will place a code on the information. The code will 
be linked to participant identity, but the link will be kept in a location that is separate from 
study data.  
• We will maintain individual study data on encrypted computers and access to the information 
will be limited to only members of the research team who need the access to properly conduct 
the study. 
• The information we send to the sponsor will not include information that directly identifies 
participants.  Instead, a code will be applied to the data and link between the code and 
individual identity will be kept at the research site. 
• Any information we publish will not identify participants directly. Identifiable information 
may be removed from the data or samples we collect, only then will biosamples be used for 
this study and any future study  
• The Research Team will make every effort to follow-up with participants and be available to 
answer questions/concerns   
 
27) Compensation for Research-Related Injury 
Although risks are unlikely, if injury should occur, treatment will in most cases be available. A 
partcipant’s insurance company may or may not pay for these costs. If a participant does not have 
insurance, or if their insurance company refuses to pay, the sponsor will pay for the cost of treating 
the injury.  The University of Miami and the sponsor are not planning to pay for pain, lost wages, and 
other costs that may incur if a participant is injured due to the research. However, participants do not 
give up any legal rights to obtain payment for an injury by after they sign the consent form. This 
policy does not prevent them from trying to obtain compensation through the legal system. 
 
28) Economic Burden to Subjects 
N/A 
29) Consent Process 
Informed consent will be done in all patients. The documentation will be attached to the protocol. 
 
Non-English Speaking Subjects 
Other than English, consent forms and study-related questionnaires will be made 
available in Spanish to participants whose primary language is Spanish, so 
prospective subjects understand the study. 
30) Process to Document Consent in Writing 
This study will be following “SOP: Written Documentation of Consent (HRP-091). 
The consent process will be initiated with study participants prior to starting any research 
procedures.  Participants will be given ample time to consider their agreement.  A member of 
the study team will be available to answer any questions throughout the length of the study 


 
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time. No one in a perceived coercive position in relation to the participant will engage in the 
consenting process.  Consent will be obtained voluntarily prior to initiating any study 
procedures. Written consent will be obtained from every patient prior to initiation of the study. 
Consents will be provided in both English and Spanish. No minors will be enrolled in this 
study. 
During the clinic visit, the consent form will be reviewed with the prospective study subject, 
and the investigator will be available to answer questions regarding procedures, risks, and 
alternatives. If subject is willing to participate, a clinic visit will be scheduled for screening 
process where CRC will obtain written informed consent from each subject. Consent will be 
obtained before any protocol-specific procedures are performed. Documentation of the 
subject’s informed consent for and participation in this study will be noted in the subject’s 
medical record. If the subject is enrolled in a sub study of this protocol, a sub study-specific 
consent must also be used. The subject representative must be provided with a copy of the 
consent form for the main study and a copy of any separate consent form for the sub study (if 
applicable).  
 
31) 
  Authorization for Use and Disclosure of Protected Health Information 
(HIPAA)  
 
 If the research team will access patient medical records or other identifiable health 
information for this research, you must obtain a waiver of the requirement for written 
authorization from the patients to access their medical records.   
 
Type of Request: 
 Waiver of Authorization for access to medical record for subject identification/recruitment. 
 Waiver of Authorization for access to medical record to obtain data for the research. 
 
Confirm that you will destroy or de-identify the information you collect at the earliest 
opportunity.  
  I confirm 
 
Confirm that the information you collect will not be reused or disclosed to any other person or 
entity, except as required by law, for authorized oversight of the research study or for other 
research for which the use or disclosure of PHI is permissible.          
   I confirm          
 
 
 
32) Drugs or Devices 
 
Pfizer will ship tofacitinib product in labeled bottles with an identifying code. Pfizer will bottle with a 
specific tablet count based on the protocol/dosing (i.e., 60 tablets in each bottle for 1 month supply) 
and the site would be responsible for labelling the bottles and dispensing. The tofacitinib pills will not 


 
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have any identifying markings. Since the study is single blind, both arms are receiving tofacitinib 10 
mg.  
 
Remote Consent & Authorization 
 
Based on FDA Guidance on the Conduct of Clinical Trials of Medical Products during the COVID-
19 Public Health Emergency, the following will be implemented during times of quarantine when in-
person, face-to-face contact is not possible. 
 
Eligible patients will be consented via Zoom for Healthcare or through an arranged three-way call 
with the potential participant, an impartial witness, and if desired and feasible, additional people 
requested by the participant, (e.g. next of kin). 
 
Once the study coordinator arranges the time and communication method for the consent process for 
a new or existing participant, or for re-consent, the study coordinator will: 
 
1. Send a copy of the consent document via secure email or U.S. Mail. 
2. Arrange for a witness to attend and witness the consent discussion. 
3. Let the participant know that a witness will join the consent meeting. 
4. Set up a Zoom meeting or 3-way call and send an invitation to the attendees. 
 
During the remote meeting the study coordinator or the person obtaining consent will: 
 
1. Identify everyone on the call. 
2. Review the informed consent with the participant, answer the participant’s questions and 
ask questions of the participant to confirm comprehension. 
3. Ask the participant if s/he consents to participate/continue participation. 
4. If the participant agrees, ask him/her to sign and date the consent document. If using 3-
way call, ask the participant to confirm s/he signed & dated the document. 
5. Ask the participant to scan or take a picture of each page of the documents and email the 
signed/dated documents to the study team. 
6. If the participant is unable to take a picture, document the circumstances. 
7. The person conducting the consent process should sign and date a copy of the consent 
document.  
8. The witness should sign & date on the witness line of a copy of the consent document.  
 
 
 
 
Documenting the Remote Consent Process 
 
The study coordinator or the person conducting the consent process should document the purpose for 
the remote consent (COVID-19), and each step of the process. A printed copy of the informed 
consent document signed by the participant, investigator and witness will be placed in the 
participant’s research record. 
 


 
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Additionally, the study coordinator or the person obtaining consent will document how s/he 
confirmed that the patient consented and signed the consent form. The note should include a 
statement indicating why the informed consent document signed by the participant was not retained, 
(e.g., due to contamination of the document by infectious material.) If the participant cannot send a 
picture of the signed document, the person obtaining consent should document why a copy of the 
signed document is not available. The note will explain why the research team does not have the 
signed and dated document.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
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References 
1. Ordas, Eckmann L, Tlamini M,Baumgart DC, Sandborn WJ. Ulcerative Colitis. The 
Lancet (2012). Nov 3;380(9853):1606-19. doi: 10.1016/S0140-6736(12)60150-0 
2. Sandborn WJ, Su C, Sands BE, et.al. Tofacitinib as Induction and Maintenance Therapy 
for Ulcerative Colitis. The New England Journal of Medicine 2017 May 4;376(18):1723- 
1736. doi: 10.1056/NEJMoa1606910. 
3. Limketkai BN, Iheozor-Ejiofor Z, Gjuladin-Hellon T, et al. Dietary interventions for 
induction and maintenance of remission in inflammatory bowel disease. Cochrane 
Library. 2019 Feb 8;2:CD012839. doi: 10.1002/14651858.CD012839.pub2. 
4. Candy S, Borok G, Wright JP, Boniface V, Goodman R. The value of an elimination 
diet in the management of patients with ulcerative colitis. S Afr Med J. 1995 
Nov;85(11):1176-9. 
5. Chiba M, Tsuji T, Nakane K, et. al. Induction with Infliximab and a Plant-Based Diet as 
First-Line (IPF) Therapy for Crohn Disease: A Single-Group Trial. The Permanente 
Journal.2017;21:17-009. doi: 10.7812/TPP/17-009. 
6. D'Haens G, Baert F, van Assche G , et al. Early combined immunosuppression or 
conventional management in patients with newly diagnosed Crohn's disease: an open 
randomised trial. The Lancet 2008 Feb 23;371(9613):660-667. doi: 10.1016/S0140- 
6736(08)60304-9. 
7. Loftus EV Jr. Update on the Incidence and Prevalence of Inflammatory Bowel Disease 
in the United States. Gastroenterol Hepatol (N Y). 2016;12(11):704–707. 
8. Ananthakrishnan, A. N., Khalili, H., Song, M., Higuchi, L. M., Richter, J. M., Nimptsch, 
K., & Chan, A. T. (2015). High school diet and risk of Crohn's disease and ulcerative 
colitis. Inflammatory bowel diseases, 21(10), 2311-2319. 
9. Ananthakrishnan AN, Khalili H, Konijeti GG, et al. Long-term intake of dietary fat and 
risk of ulcerative colitis and crohn's disease. Gut. 2014;63(5):776-784. 
10. Racine A, Carbonnel F, Chan SS, Hart AR, Bueno-de-Mesquita HB, Oldenburg B, 
van Schaik FD, Tjønneland A, Olsen A, Dahm CC, Key T. Dietary patterns and risk of 
inflammatory bowel disease in Europe: results from the EPIC study. Inflammatory bowel 
diseases. 2015 Dec 30;22(2):345-54. 
11. Afzali, Anita, and Raymond K. Cross. Racial and ethnic minorities with inflammatory 
bowel disease in the United States: a systematic review of disease characteristics and 
differences. Inflammatory Bowel Diseases 22.8 (2016): 2023-2040 
12. Rangan P, Choi I, Wei M, et al. Fasting Mimicking Diet Modulates Microbiota and 
Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology. Cell 
Rep. 2019 Mar 5;26(10):2704-2719.e6. doi: 10.1016/j.celrep.2019.02.019. 
13. Cabo de Rafael, Mark P.Mattson. Effects of Intermittent Fasting on Health, Aging, and 
Disease. 
The 
New 
England 
Journal 
of 
Medicine.2020 
Jan 
16;382(3):298. 
doi:10.1056/NEJMx190038. 
14. Betteridge JD, Armbruster SP, Maydonovitch C, Veerappan GR. Inflammatory bowel 
disease prevalence by age, gender, race, and geographic location in the US military 
health care population. Inflammatory bowel diseases. 2013 Jun 1;19(7):1421-7. 
15. Wu, G. D. et al. Linking long-term dietary patterns with gut microbial enterotypes. 
Science (New York, N.Y.) 334, 105-108, doi:10.1126/science.1208344 (2011). 


 
IRB Study Number: 20200436 
Date: Version 3, 10/05/2021 
 
Page 24 of 23 
 
16. Ni, J., Wu, G. D., Albenberg, L. & Tomov, V. T. Gut microbiota and IBD: causation or 
correlation? 
Nature 
reviews. 
Gastroenterology 
& 
hepatology 
14, 
573-584, 
doi:10.1038/nrgastro.2017.88 (2017) 
17. Devkota, S. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion 
and colitis in Il10- /- mice. Nature 487, 104-108, doi:10.1038/nature11225 (2012) 
18. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. 
Nature 505, 559-563, doi:10.1038/nature12820 (2014) 
19. Huda-Faujan, N. et al. The impact of the level of the intestinal short chain Fatty acids 
in inflammatory bowel disease patients versus healthy subjects. The open biochemistry 
journal 4, 53-58, doi:10.2174/1874091x01004010053 (2010) 
20. Damman, C. J., Miller, S. I., Surawicz, C. M. & Zisman, T. L. The microbiome and 
inflammatory bowel disease: is there a therapeutic role for fecal microbiota 
transplantation? 
The 
American 
journal 
of 
gastroenterology 
107, 
1452-1459, 
doi:10.1038/ajg.2012.93 (2012). 
21. Vaughn, B. P. et al. Increased Intestinal Microbial Diversity Following Fecal Microbiota 
Transplant for Active Crohn's Disease. Inflammatory bowel diseases 22, 2182-2190, 
doi:10.1097/mib. (2016). 
22. Sun, M., Wu, W., Liu, Z. & Cong, Y. Microbiota metabolite short chain fatty acids, 
GPCR, and inflammatory bowel diseases. Journal of gastroenterology 52, 1-8, 
doi:10.1007/s00535-016-1242-9 (2017). 
23. D'Souza, W. N. et al. Differing roles for short chain fatty acids and GPR43 agonism 
in the regulation of intestinal barrier function and immune responses. PloS one 12, 
e0180190, doi:10.1371/journal.pone.0180190 (2017) 
24. Wu, G. D. The Gut Microbiome, Its Metabolome, and Their Relationship to Health and 
Disease. Nestle Nutrition Institute workshop series 84, 103-110, doi:10.1159/000436993 
(2016) 
25. Bloom, S. M. et al. Commensal Bacteroides species induce colitis in host-genotype- 
specific fashion in a mouse model of inflammatory bowel disease. Cell host & microbe 9, 
390-403, doi:10.1016/j.chom.2011.04.009 (2011). 
26. De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative 
study in children from Europe and rural Africa. Proceedings of the National Academy of 
Sciences 
of 
the 
United 
States 
of 
America 
107, 
14691-14696, 
doi:10.1073/pnas.1005963107 (2010). 
27. Ni, J. et al. A role for bacterial urease in gut dysbiosis and Crohn's disease. Science 
translational medicine 9, doi:10.1126/scitranslmed.aah6888 (2017) 
28. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in 
consumption of omega-3 and omega-6 fatty acids in the United States during the 20th 
century. The American journal of clinical nutrition. 2011 May 1;93(5):950-62. 
29. Davis N., Schechter CB, Ortega F., et al. Dietary patterns in blacks and Hispanics 
with diagnosed diabetes in New York City's South Bronx. Am J Clin Nutr. 2013; 97:878- 
85. 
30. Sandborn, W. J., Su, C., Sands, B. E., D’Haens, G. R., Vermeire, S., Schreiber, S., & 
Friedman, G. (2017). Tofacitinib as induction and maintenance therapy for ulcerative 
colitis. New England Journal of Medicine, 376(18), 1723-1736. 
31. 
National Health and Nutrition Surveys NHANES Nutrient, National Cancer Institute, 
epi.grants.cancer.gov/diet/usualintakes/ffq , Division of Cancer Control and Population 
Sciences.


 
IRB Study Number: 20200436 
Date: Version 3, 10/05/2021 
 
Page 25 of 23 
 
32. The ProLon Fasting Mimicking Diet is the only dietary program patented for promoting 
longevity and healthspan. Prolon https://prolonpro.com/. Published February 2017. 
33. Wei M, Brandhorst S, Shelehchi M, et.al. Fasting-mimicking diet and markers/risk 
factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational 
Medicine. 2017 Feb 15;9(377). pii: eaai8700. doi: 10.1126/scitranslmed.aai8700. 
34. Durchschein F, Petritsch W, Hammer HF. Diet therapy for inflammatory bowel 
diseases: The established and the new. World Journal of Gastroenterology. 2016 Feb 
21;22(7):2179-94. doi: 10.3748/wjg.v22.i7.2179. 
35. Owczarek D, Rodacki T, Domagała-Rodacka R, Cibor D, Mach T. Diet and nutritional 
factors in inflammatory bowel diseases. World Journal of Gastroenterology 2016 Jan 
21;22(3):895-905. doi: 10.3748/wjg.v22.i3.895. 
36. 
Chilton FH, Murphy RC, Wilson BA, et al. Diet-gene interactions and PUFA 
metabolism: A potential contributor to health disparities and human diseases. Nutrients. 
2014;6(5):1993-2022. 
37. Chilton FH, Dutta R, Reynolds LM, Sergeant S, Mathias RA, Seeds MC. Precision 
Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for Personalized 
Supplementation Approaches for the Prevention and Management of Human Diseases. 
Nutrients. 2017 Oct 25;9(11):1165. 
38. Wei M, Brandhorst S, Shelehchi M, et al. Fasting-mimicking diet and markers/risk 
factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational 
Medicine. 2017 Feb 15;9(377). pii: eaai8700. doi: 10.1126/scitranslmed.aai8700. 
37. Sandborn, W. J., Su, C., Sands, B. E., D’Haens, G. R., Vermeire, S., Schreiber, S., 
.& Friedman, G. (2017). Tofacitinib as induction and maintenance therapy for ulcerative colitis. New 
England ournal of Medicine, 376(18), 1723-1736 
39. David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. 
Nature 505, 559-563, doi:10.1038/nature12820 (2014). 
40. Dolan, K. T. & Chang, E. B. Diet, gut microbes, and the pathogenesis of inflammatory 
bowel diseases. Molecular nutrition & food research 61, doi:10.1002/mnfr.201600129 
(2017). 
41. Walker, A. W. et al. Dominant and diet-responsive groups of bacteria within the human 
colonic microbiota. The ISME journal 5, 220-230, doi:10.1038/ismej.2010.118 (2011). 
42. Lucas, C. J., Galettis, P. & Schneider, J. The pharmacokinetics and the 
pharmacodynamics of cannabinoids. 
Br J Clin Pharmacol 84, 
2477-2482, 
doi:10.1111/bcp.13710 (2018). 
43. Atsmon, J. et al. PTL401, a New Formulation Based on Pro-Nano Dispersion 
Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers. J Pharm 
Sci 107, 1423-1429, doi:10.1016/j.xphs.2017.12.020 (2018). 
44. Ananthakrishnan AN, Luo C, Yajnik V, et. al.Gut Microbiome Function Predicts 
Response to Anti-integrin Biologic Therapy in Inflammatory Bowel Diseases. Cell Press 
2017 May 10;21(5):603-610.e3. doi: 10.1016/j.chom.2017.04.010. 
45. Torres, J. et al. Infants born to mothers with IBD present with altered gut microbiome 
that transfers abnormalities of the adaptive immune system to germ-free mice. Gut 69, 
42-51, doi:10.1136/gutjnl-2018-317855 (2020). 
46. Britton, G. J. et al. Microbiotas from Humans with Inflammatory Bowel Disease Alter 
the Balance of Gut Th17 and RORgammat(+) Regulatory T Cells and Exacerbate Colitis 
in Mice. Immunity 50, 212-224.e214, doi:10.1016/j.immuni.2018.12.015 (2019)


 
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1 
 
IRB Study Number: 20200436 
Date: Version 3, 10/05/2021 
 
 


 
 
 
 
 
 
 
 

ICF_001.pdf: 
 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 1 OF 17 
 
A randomized control study to examine the influence of a healthy diet on moderate to severe 
ulcerative colitis patients undergoing tofacitinib induction 
 
 
 
National Clinical Trial (NCT) identified Number: NCT04505410 
 
 
 
Principal Investigator: Oriana M. Damas, MD MSCTI 
 
 
 
Sponsor: University of Miami Miller School of Medicine 
 
 
 
Funded by: Pfizer (PI-initiated Study) 
 
 
 
Version Number: 3, 10/23/2023 
 
 
 
 
IRB Study Number: 20200436 
 
 
 
 
 
 
 
 
 
 
 
 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 2 OF 17 
 
 
Title of Study: A randomized control study to examine the influence of a healthy diet on moderate to 
severe ulcerative colitis patients undergoing tofacitinib induction  
Principal Investigator: Dr. Oriana Damas   
Department:  Gastroenterology 
Phone Number:  305-243 2515 
Study Contact Dr. Oriana Damas   
Study Contact Telephone Number: 305-243 2515  
Dietitian Contact: Luis Garces 
Study Contact Telephone Number: 305-243-6982 or 305-243-8644 (24-hours) 
Study Contact Email: lgarces@med.miami.edu 
 
A person who takes part in a research study is called a research or study subject. In this consent form 
“you” always refers to the research subject.  
 
Key Information about This Research Study 
 
You are being asked to volunteer for a research study being conducted on people who have moderate to 
severe ulcerative colitis (an inflammatory disease of the bowel). You are asked to be in this study because 
you have this medical condition. This form will tell you about the procedures used for the study, the risk 
of your participation, and other important information that you will need to know.  If you have questions 
about this form, or find words that are not clear to you, please let the investigators know and they will 
be happy to answer all your questions. 
 
Almost all research studies involve some risk. Risks of this study are more than minimal. These risks 
are described in detail later in this document.  
The purpose of this study is to use diet as adjunctive treatment (another treatment used together with 
the primary treatment) for ulcerative colitis (UC) patients who will be starting tofacinitib or other 
biologic medication induction as part of their plan of care. This study seeks to identify changes in your 
intestinal flora occurring as a result of the diet intervention combined with your tofacinitib or other 
biologic medication treatment plan. The diet is not part of your standard of care treatment and is being 
done for research purposes. It is to be used as an adjunctive therapy to the standard drug therapy 
prescribed by your doctor. We will also measure baseline diet patterns and stool for changes in the 
intestinal flora and compare them to any changes occurring after diet intervention. The results of this 
research study will be used to determine if a diet intervention improves the effects of tofacitinib or 
other biologic medication on clinical response.  


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 3 OF 17 
 
Your participation in this study is voluntary. You do not have to participate in this study if you do not 
want to and you can leave the study at any time. You will not lose any services, benefits, or rights you 
would normally have if you choose not to participate or if you leave the study early.  
The remainder of this form contains a more complete description of this study. Please read this 
description carefully. You can ask any questions you need to help decide whether or not to join this 
study.  
What if I have Questions?  
If you have questions, concerns, or complaints, or think the research has hurt you, talk to the research 
team Gabriella Grau at 305-243-6405. 
This research has been reviewed and approved by an Institutional Review Board (“IRB”). The Human 
Subject Research Office (HSRO) provides administrative support to the University of Miami’s IRBs. 
Please call the HSRO at 305-243-3195 if:    
- 
Your questions, concerns, or complaints are not being answered by the research team.   
- 
You cannot reach the research team.             
- 
You want to talk to someone besides the research team. 
- 
You have questions about your rights as a research subject. 
- 
You want to get information or provide input about this research. 
How is being in this study different from my regular health care? 
This study is not part of your standard of care and you may choose not to be in the study. 
 
How is this research funded?  
This research is being funded by Pfizer Global Medical Grants, also called the sponsor. Sponsors may 
change or be added. 
 
What happens if I say yes, I want to be in this research? 
To participate in the study, you need to be between the ages of 18 and 70 years old, diagnosed with 
moderate to severe ulcerative colitis and starting tofacinitib or other biologic medication therapy (as 
determined by your treating physician). We will be enrolling a total of 76 subjects and we will have 
two different groups, Arm 1 and Arm 2 (38 subjects per arm), both with an 8-week time duration of 
dietary recommendations that also coincide with the period of induction with tofacitinib or other 
biologic medication. Eligible participants will be randomly assigned (like flipping a coin) to either 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 4 OF 17 
 
Arm 1 or Arm 2 by an independent researcher. The patients are blinded to which study arm they will 
be placed in and therefore you will not be able to know whether you were assigned the dietary 
intervention. 
After you have completed all of the screening criteria and you have qualified for the study, you will be 
randomly assigned to either Arm 1 or Arm 2 of this study.  
 
All participants will have initial baseline assessments including: a detailed IBD questionnaire, an IBD 
Quality of Life (IBD QoL) questionnaire, a Simple Clinical Colitis Activity Index (SCCAI), food/diet 
assessments, including a 24-hour food recall and general food frequency questionnaire, a serum blood 
draw, and stool sample measurements of fecal calprotectin, microbiome and metabolites.  Food/diet 
assessments will be repeated during week 4-5, as well as detailed food diaries. Study dietician may 
provide nutritional supplements and/or other dietary guidance to you. Biosample collection will be 
repeated again for all participants in week 7. If not possible, we will arrange with a local lab to collect 
samples and send them with an overnight currier. A last assessment of clinical response, medication 
updates, IBD QoL and food/diet assessments will be performed at the end of the week 8 induction period.  
You will receive diet counseling and information on good eating habits by our dietitian, you will need 
to come only two times to collect stool and collect blood samples. The rest of the follow up will be by 
phone/emails.  
 
Your participation in the study will last approximately 8 weeks. The tests that will be performed are 
shown in Table 1. They will consist of measures of inflammation, gut bacteria, body composition, 
dietary intake, and quality of life. 
 
 
Timeline for Study Assessments for Participants with Ulcerative Colitis can be found in Table 1 
(next page) 
 
 
 
 
 
 
 
 
 
 
 
 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 5 OF 17 
 
 
 
 
Table 1. 
 
 
  
 
If you qualify for and decide to participate in the study, you will come to offices located at either one 
of our locations 1475 NW 12 Ave or at Crohn's and Colitis Center and 1120 NW 14 street, 14th floor 
offices at the University of Miami Miller School of Medicine. You will be asked a number of questions 
about your health, including how you feel and your diet (see Table 1). 
 
For this study, you will also have blood drawn twice: at baseline and again at week 7 (see Table 1). You 
do not need to be fasting for any of the blood draws and each blood draw will be approximately 1.5 
teaspoons or 7 ml.  
 
You will also be asked to provide morning stool for the study of the gut bacteria and for clinical 
parameters such as parasites.  This will occur twice: at baseline and again at week 7 (see Table 1). 
 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 6 OF 17 
 
We will be taking several of your physical measurements, including your weight height, and will 
calculate your body mass index.  
 
You will receive phone calls from your coordinator or dietitian during the study on a scheduled basis.  
 
You will be asked to complete an online dietary assessment. These include a validated food-frequency 
questionnaire (FFQ) and the ASA-24. The FFQ and ASA-24 will be self-administered, but guidance will 
be provided if needed by one of our research team staff members. Additionally, you will need to record 
everyday all the food you eat in a food diary or take pictures of your food and email them to a secure 
email address. Our research staff will provide the special email address to you.  
 
What are my responsibilities if I take part in this research? 
If you take part in this research, you will be responsible for:  
 
• Providing samples of blood and stool at baseline and week 7 
• Completing all written and electronic study-related questionnaires  
• Adhering to study dietary recommendations to the best of your ability  
• Recording all the food you eat in written food diary or electronic photos sent to secure email 
during a designated time period 
• Communicating with the study dietitian/coordinator for scheduled phone calls or general 
questions you may have about the study  
• Communicating with your medical provider about any discomforts, side effects, or health-related 
concerns 
 
 
What happens if I want to leave the study?  
Your participation in this study is voluntary. You may decide not to participate, or you may leave the 
study at any time. If you decide to leave the study, contact the study team so the study doctor can work 
with you to create a safe plan for your withdrawal.  Your decision will not result in any penalty or loss 
of benefits to which you are entitled. Your participation in this study may be stopped at any time by the 
study doctor or the sponsor without your consent for any reason, including: 
•   if it is in your best interest 
•  if you do not consent to continue in the study after being told of changes in the research that may affect 
you 
 
If you leave the research, we will keep the information about you and the samples (blood, stool, or other 
samples) we obtained from you. This data will remain as part of the study database and may not be 
removed.  


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 7 OF 17 
 
 
If you leave the research, we would like to keep checking on your health. We will ask if we can review 
your medical record and collect data about your medical care in the future.  If you agree to allow us to 
keep collecting data after you stop being in the study, this new data will be handled the same as the other 
research data.  
 
If you feel you have been treated unfairly, or you have questions regarding your rights as a research 
subject, you may contact University of Miami Human Subjects Research Office at 1500 NW 12th 
Avenue, Suite 1002, Miami, FL 33136, (305) 243-3195. 
 
What are my other choices if I do not take part in this study? 
This is not a treatment study. You may choose not to be in this study 
 
Is there any way being in this study could be bad for me?  
Certain risks are associated with your participation in the study: 
The process of interviewing may cause you distress and discomfort because you will be talking about 
your personal activities and thoughts. 
 
It is possible that some of the questions that are asked of you are similar or the same as others asked by 
other health professionals and you may wonder why it is necessary to answer them again.  It may be 
tiresome to you to be asked these questions again. 
 
The investigator will also make a judgment about your ability to understand this consent form and your 
ability to participate in the interview.  If in his or her opinion the interview is causing you distress, or 
you are not yet well enough to participate, you will be thanked for your time and the investigator will 
not proceed.  It may be possible that you will again be invited to participate when your health has 
improved. 
 
If you find any of these feelings uncomfortable, please report them to any of the study doctors and your 
participation in the study will be re-evaluated.  If you find any of these feelings too uncomfortable, you 
may ask to be removed from the study. 
 
In addition, you may experience discomfort or fatigue in having the study doctors ask you questions on 
the phone, in person, and with the questionnaires.  The risks of answering questions are minimal, but 
you can stop at any point if you feel too tired to continue with the assessments. 
 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 8 OF 17 
 
The risks of blood drawing include fainting, temporary pain, and/or bruising at the site of the needle 
stick.  Rarely, infection or the formation of a small clot or swelling of the vein and surrounding area may 
occur. 
 
If you are planning to become pregnant, or become pregnant during your participation in this study, 
you are advised to speak to your medical provider as the dietary recommendations and tofacitinib or 
other biologic medications may pose unforeseeable risks to you and the embryo or fetus. 
 
Although the samples used for the current study are coded, there is still a risk to your privacy when 
you share information about yourself. However, all the data that can be linked to the samples is saved 
with password-protected databases and only authorized personnel can access them.  
 
You may not like the particular dietary guidance given to you and the food may not be to your liking. 
You may also have more hunger than when on your normal diet if you have a baseline diet that is high 
in calories.  
 
 
New Findings  
You will be told about any new information that might change your decision to be in this study. 
 
 
Will being in this study help me in any way? 
 
You may not benefit directly from participating in this study, although it is possible that you experience 
improvement in your medical symptoms if the diet intervention is effective. However, this benefit may 
decrease or end once you stop participating in the study and if you choose to go back to eating your 
regular diet.   
 
Any information obtained from this research study that is important to your health will be shared with 
you. 
 
You may wish to discuss continuing to learn more about diet and nutrition with your physician if you 
feel that this type of diet is helpful for your medical symptoms. 
 
 
Will being in this study cost me anything? 
 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 9 OF 17 
 
You will not incur any direct costs by participating in this study. You and/or your health-care 
payer/insurance company will not be billed for study visits or procedures or for the research tests that 
are described in this form required by the study.  
 
You or your healthcare payer/insurance company will still be responsible for any diagnostic evaluations 
or treatment, including medications, required by your medical condition. 
 
There are no costs to you for participating in this research study. All the tests, procedures and delivered 
meals and snacks for this study will be provided to you at no cost. 
 
Will I be paid or receive anything for being in this study? 
 
For your participation in this study you will be compensated a total of $60 in monetary gift cards.  
 
Study compensation will be disbursed in the following order: You will receive a $30 gift card after 
completing Visit 1, this includes your initial baseline questionnaires, blood draw and stool kit.  You will 
receive a $30 gift card after completing Visit 2 (week 7), this includes follow-up questionnaires, and a 
second set of blood draw and stool kit. If you choose to receive the total of $60 gift cards at once, you 
can receive them at the end of Visit 2, and only after completion of Visit 1 and Visit 2.  
 
If you decide to withdraw from the study, you will only be compensated for any study visit completed.  
 
We will also provide you with instructions and possible dietary recommendations.   
 
Additionally, you will receive the tofacitinib pills if prescribed by your doctor for a total of 8 weeks. 
This will not be processed through your insurance and will not require authorization. However, 
authorization of your insurance will be required for tofacinitib after 8 weeks. If you are starting other 
biologic medications, authorization of your insurance will be required.   
 
If you drive to our medical center and park in the valet parking at the Sylvester Comprehensive Cancer 
Center, your parking ticket will be validated each time you have to visit the clinic through your 
participation in this study. 
 
The University of Miami may retain, preserve, or dispose of study specimens and may use these 
specimens for research which may result in commercial applications. You will not receive money for 
donating blood, urine or tissue samples nor will you receive money from any future proceeds as a result 
of this research project 
 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 10 OF 17 
 
 
What happens to the information collected for the research? 
 
We will do our best to limit the use or disclosure of your personal information, including information 
from this research study and from your medical records, to people who have a need to review this 
information. We cannot promise complete confidentiality. Some organizations may be required to 
inspect and copy your information including the IRB and other University of Miami representatives 
responsible for the management or oversight of this study. 
We have strict rules to protect your personal information and protected health information (PHI). We 
will limit who has access to your name, address, phone number, and other information that can identify 
you.  
We will remove identifiable information from the data we collect about you. After we remove all of the 
identifiers, we will place a code on the information. The code will be linked to your identity, but the link 
will be kept in a location that is separate from your study data. We will maintain your study data on 
encrypted computers and access to the information will be limited to only members of the research team 
who need the access to properly conduct the study. 
 
The information we send to the sponsor will not include information that directly identifies you.  Instead, 
a code will be applied to the data and link between the code and your identity will be kept at the research 
site.  
 
We may publish and present what we learn from this study, but none of this information will identify 
you directly without your permission. Information which can identify you may be removed from the data 
or samples we collect, and after such removal, the data or samples could be used for future research 
studies or provided to another researcher for future research without additional informed consent. 
The following is a list of individuals who may access your records:   
• Members of the research team  
• Offices and committees responsible for the oversight of research 
• U.S. Office for Human Research Protections  
• The U.S. Food and Drug Administration (FDA) 
• Regulatory Authorities from other countries 
• The study sponsor 
• Collaborating researchers outside of the University of Miami, including researchers at Emory 
University  
 
The study doctor and research team may publish the results of this research. However, they will keep 
your name and other identifying information confidential. 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 11 OF 17 
 
If you are, or have been, a patient at a University of Miami facility, you will have a University of Miami 
medical record.  We use an electronic medical record system known as UChart, which improves access 
to information important to your medical care. UChart will show that you are in a research study and a 
copy of this signed consent form will be included. To provide as complete a record as possible, some or 
all of your study-related research information may also be placed in UChart. This specifically includes 
investigational drugs, devices, biologics, or anything else that may, separately or together with other 
substances or activities, interfere with your clinical treatment or place you at greater risk of harm. Other 
information from the research study may be included as well.  Including this information in the electronic 
medical record system is intended only to give information to caregivers providing treatment for you 
while you are on this study. 
 
This information will be available to University of Miami doctors, nurses and other authorized staff who 
may not be part of the research team but who are involved in providing you medical care, or who are 
otherwise allowed to access your information.  The confidentiality of the results and other documents in 
UChart will be governed by laws, such as HIPAA, that concern medical records. We suggest that you 
tell any non-University of Miami doctors that you are in a research study and that more information may 
be made available to them at your request. The research team may use your information to notify you of 
appointments, send you appointment reminders, or schedule additional appointments. 
information. Information about these new infections is used to track these diseases statewide and 
nationwide.  Other than this required reporting, your results will be kept confidential to the extent 
permissible under the law. The health department may contact you with resources for counseling and 
medical care, if you need them and want them.   
 
The monitors, auditors, IRB, and regulatory authorities will be granted direct access to your original 
medical records for verification of clinical trial procedures and data, without violating the confidentiality 
of the subject, to the extent permitted by applicable laws and regulations. By signing this consent 
document, you authorize such access.  
 
Federal law provides additional protections of your medical records and related health information. 
These protections are described in the University of Miami HIPAA authorization for research, part 2 of 
this document. 
 
Will I receive any results from this research?  
 
Most tests done on samples in research studies are only for research and have no clear meaning for health 
care.  If the research, with your identifiable information or samples, gives results that do have meaning 
for your health, the researchers will contact you to let you know what they have found.  
  


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 12 OF 17 
 
Will information or leftover specimens be used for other research?  
 
Information collected about you and biospecimens collected from you will be used for this research and 
may also be used for other research studies here at the University of Miami.  We may also share the 
information and specimens with other institutions for research.  Before using the information and 
specimens for other research, the study team will remove information that identifies you so the 
individuals performing the research will not know who the information and specimens came from.  We 
will not ask for additional consent from you to use your information and specimens for the additional 
research.   
 
May we contact you by e-mail?   
 
We are requesting your email address so we can send surveys that you may need to complete in a timely 
manner.  Email is generally not a secure way to communicate about your health, as there are many ways 
for unauthorized users to access email. You should avoid sending sensitive, detailed personal 
information by email. Email should also not be used to convey information of an urgent nature. If you 
need to talk to someone immediately, please contact Odalys Guerrero 305-243-6405.  
 
You do not have to provide your email address to participate in this study. Please initial one of the lines 
below. 
_____  Yes, may use email to contact me for this study. My email address is: _____________________ 
_____  No, I do not want to be contacted by email.  
 
 
Confidentiality  
 
There is a slight risk that you may be identified if you take part in this study.  However, every effort will 
be made to protect your identity. The blood sample will be assigned a number Your records and results 
will not be identified as pertaining to you in any publication without your expressed permission.  The 
Investigator and his collaborators, staff, and the sponsor will consider your records confidential to the 
extent permitted by law.  Your records may also be reviewed for audit purposes by authorized University 
of Miami employees or other agents who will be bound by the same provisions of confidentiality. 
 
If you should seek treatment at the University of Miami, information from this study may be given to 
the treating physicians and other medical staff at the Miller School of Medicine.  In turn, the treating 
physicians and other medical staff at the Miller School of Medicine may provide information about your 
treatment and care to the study doctor and/or agents for the study doctor. 
 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 13 OF 17 
 
 
What happens if I am injured or get sick because of this study? 
 
Although risks are unlikely, if injury should occur, treatment will in most cases be available. If you have 
insurance, your insurance company may or may not pay for these costs. If you do not have insurance, or 
if your insurance company refuses to pay, the sponsor will pay for the cost of treating the injury.  The 
University of Miami and the sponsor are not planning to pay for pain, lost wages, and other costs you 
incur because you were hurt. You do not give up any of your legal rights to obtain payment for an injury 
if you sign this consent. This policy does not prevent you from trying to obtain compensation through 
the legal system. 
 
 
Future Contact 
We would like to be able to contact you in the future for any modifications of this study or for any future 
studies.  Your decision will not affect your ability to participate in this study. 
 
Please initial next to one of the following responses: 
 
______ Yes, I agree to be contacted in the future. 
 
______ No, I do not wish to be contacted in the future. 
 
 
WHERE CAN YOU FIND MORE INFORMATION ABOUT THIS STUDY?  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this web site at any time. 
 
WHOM TO CONTACT FOR ANSWERS 
 
If you have any questions or concerns about this research, feel free to ask for additional information from 
the study doctor or if at any time you feel you have experienced a research-related injury, contact Oriana 
M. Damas, M.D. at 305-243-8644 (UMGI) 24h a day, 7 days a week; or  
Should you have questions regarding your rights as a research subject, you may contact: 
 
University of Miami 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 14 OF 17 
 
Human Subjects Research Office 
1400 NW 10th Avenue, Suite 1200A 
Miami, FL 33136 
Phone: 305-243-3195 
 
Do not sign this consent form unless you have had a chance to ask questions and have received 
satisfactory answers to all of your questions. 
If you agree to be in this study, you will receive a signed and dated copy of this consent form for your 
records. 
 
HIPAA Protections 
Federal law provides additional protections of your medical records and related health information. 
These protections are described in the second part of this document, University of Miami HIPAA 
Authorization for Research. 
 
 
AGREEMENT OF DECISION TO PARTICIPATE 
I have read this consent, which is printed in English (a language which I read and understand).  This 
study has been explained to my satisfaction and all of my questions relating to the study procedures, 
risks and discomforts, and side effects have been answered.  If I have any further questions regarding 
this study, or in the event of a study-related injury, I should contact the appropriate person named above.  
Based on this information, I voluntarily agree to give permission (consent) for me to take part in this 
study. 
______________________________________________________ 
 
Printed name of participant 
 
______________________________________________________    
______________ 
Signature of participant 
Date 
 
______________________________________________________                                               
Printed Name of person conducting informed consent 
 
 
_______________________________________________  
 
 _________________ 
Signature of person conducting Informed Consent                                         Date                              
 
 
 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 15 OF 17 
 
 
 
PART 2:  UNIVERSITY OF MIAMI/JACKSON HEALTH SYSTEMS 
 
HIPAA AUTHORIZATION FOR RESEARCH   
 
What is the purpose of this part of the form?  
State and federal privacy laws protect the use and release of your personal health information. Under 
these laws, your health care providers generally cannot release your health information for the research 
listed above unless you give your permission. You will use this form to give your permission.  By signing 
this form, you authorize the University of Miami, Jackson Health Systems, the Principal Investigator 
and his/her/their/its collaborators and staff to obtain, use and disclose your health information, as 
described below. These people and institutions are called “Providers” in this form.  
 
What Personal Health Information will be used or shared?  
You are authorizing the use and sharing of all of the information collected or created during this research 
as described in the first part of this document, including information in your medical records that is 
relevant to this research study.  Information that may be relevant includes: 
• Your past medical history,  
• Medical information from your primary care physician,  
• All other medical information relating to your participation in the study listed at the top of this 
document 
 
Who may receive my Personal Health Information? 
The Providers may use and share your health information with: 
• The Principal Investigator and his/her research staff 
• Representatives of government agencies that have oversight of the study or who the law permits to 
access the information such as the U.S. Food and Drug Administration, the Department of Health 
and Human Services, and the Florida Department of Health    
• Groups that collaborate and sponsor research (Cooperative Groups) 
• Institutional Review Boards (groups of people who oversee research) 
• Other persons who watch over the safety, effectiveness, and conduct of research 
• The Sponsor of the research, its agents, monitors, and contractors 
• Other participating researchers; and  
• Independent data and safety monitoring boards    
 
Authorized staff such as doctors and nurses who are taking care of your but are not involved in this 


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 16 OF 17 
 
research may be aware that you are participating in a research study and may have access to research 
information about you. If the study is related to your medical care, any study-related information may 
be placed in your permanent hospital, clinic, or physician’s office records. 
Why will my Personal Health Information be used and disclosed? 
• Researchers (those individuals in charge of the study) and research team members will use your 
information to conduct the research study described in this informed consent document and other 
activities related to the research, such as evaluating the safety of the study. 
• The research sponsor and its authorized representatives, business partners, clinical research 
organizations and affiliates will use your information for the purposes described in this informed 
consent document and for other activities related to the research, such as assessing the safety or 
effectiveness of the drug, device or treatment being studied, improving designs of future studies or 
obtaining approval for new drugs, devices or health care products.   
• The University of Miami’s clinical trial organizations will use your information to review and 
support clinical trials at the University.  
• Other University of Miami offices involved in regulatory compliance, including the Institutional 
Review Board (IRB), Offices of General Counsel and Compliance, may use your information to 
ensure the research is performed correctly.   
• U.S. government agencies, such as the Food and Drug Administration and the Office for Human 
Research Protections, government agencies from other countries, and others who are authorized by 
law may use your information to review or oversee this research or to see if a new drug, device or 
other health care product should be approved for marketing.  
 
What other information should I know?  
1. Once your information has been disclosed to a third party, the federal privacy law may no longer 
protect the information from further disclosure.   
2. You do not have to sign this Authorization, but if you do not sign it, you may not participate in the 
research and receive the research treatment; however, your right to other medical treatment will not 
be affected.   
3. You may change your mind and revoke (take back) this Authorization at any time and for any reason. 
To revoke this Authorization, you must write to the study doctor or to the Human Subjects Research 
Office at 1400 NW 10th AVE, Suite 1200A, Miami FL  33136.   
4. If you revoke this Authorization, you will not be able to continue taking part in the research. Also, 
even if you revoke this authorization, the institutions and people listed above will continue to use 
and disclose the personal information they have already collected if the information is needed to 
protect the reliability of the research.   
5. While the research is in progress, you will not be allowed to see your health information that is 
created or collected by the institutions and people listed above. After the research is finished, you 
may see your health information.  


 Permission to Take Part in a Human Research Study 
 
 
 
 
NAME: 
_________________________________ 
 
MRN: __________________________________ 
 
AGE: ___________ DOB: _____/_____/______ 
 
PAGE 17 OF 17 
 
6. This Authorization does not have an expiration date.  There is no set date at which your information 
will be destroyed or no longer used because the research will need to analyze the information for 
many years and it is not possible to know when they will complete the analysis.  
7. You will be given a copy of this authorization after you sign it.  
 
 
Signature of participant or participant’s legal 
representative 
 
Printed name of participant 
       
 
       Date