Conditions: Ulcerative Colitis Inflammatory Bowel Diseases
Keywords: FMT Fecal Microbiota Transplantation Inflammatory Bowel Diseases
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 27
Healthy volunteers: no

Brief summary:
A double-blind, randomized, placebo-controlled clinical trial examining the efficacy and safety of Fecal Microbiota Transplantation (FMT) and high fiber supplementation in patients with active mild to moderate Ulcerative Colitis (UC). All enrolled subjects will provide serological, stool and mucosal specimen at each clinic visit to help further define the alterations in microbial profiles and immune cell function in response to psyllium fiber after FMT treatment.

Detailed description:
This is a randomized, double-blind, placebo-controlled clinical trial with the following treatment assignments:

1. Investigational FMT (one-time)

   1. Subject will blindly receive investigational FMT once at day 0 colonoscopy
   2. Subjects in this group will blindly receive placebo FMP250 at week 8 by flexible sigmoidoscopy.
2. Investigational FMT (one-time) + Psyllium (2x/day for 8 weeks)

   1. Subject will blindly receive investigational FMT once at day 0 colonoscopy
   2. Subjects in this group will blindly receive placebo FMP250 at week 8 by flexible sigmoidoscopy.
3. Placebo FMT (one-time) +/- Psyllium (2x/day for 8 weeks)

   1. Subject will blindly receive placebo FMT once at day 0 colonoscopy
   2. Subjects in this group will blindly receive investigational FMP250 at week 8 by flexible sigmoidoscopy.

Subjects will blindly receive the investigational or placebo FMP250 treatment if they meet all inclusion and exclusion criteria during the day 0 screening colonoscopy. Subjects will receive follow-up phone calls at day 1, week 2, week 6, and week 10 post-FMT and will return for clinic visits at week 4, week 8 and week 12 post-FMT. Stool and blood samples will be collected for research purposes from subjects at every clinic visit (Day 0 colonoscopy, Week 4, Week 8, and Week 12). Mucosal biopsies will also be taken during the initial colonoscopy, at day 0 and during the follow-up flexible sigmoidoscopy at week 8. At week 8 post-FMT, all subjects will be evaluated by flexible sigmoidoscopy. Subjects originally randomized into the placebo cohort at week 0 will receive investigational FMP250 by flexible sigmoidoscopy at week 8, and subjects originally randomized into the investigational cohort at week 0 will receive placebo FMP250 by flexible sigmoidoscopy at week 8. Lastly, all subjects will be contacted for follow-up phone calls every subsequent 6 months for the next year.

Arms:
arm 1: Participants will be blindly randomized to receive a single dose of investigational FMT during the week 0 colonoscopy.

Additionally, participants will blindly receive a single dose of placebo FMT during the week 8 by flexible sigmoidoscopy. arm 2: Participants will be blindly randomized to receive a single dose of investigational FMT during the week 0 colonoscopy. They will also receive fiber supplementation of 1 teaspoon 2x/day for 8 weeks.

Additionally, participants will blindly receive a single dose of placebo FMT during the week 8 by flexible sigmoidoscopy. arm 3: Participants will be blindly randomized to receive a single dose of placebo FMT during the week 0 colonoscopy. They may or may not also receive fiber supplementation of 1 teaspoon 2x/day for 8 weeks.

Additionally, participants will blindly receive a single dose of investigational FMT during the week 8 by flexible sigmoidoscopy.

Interventions: intervention 1: Fecal Microbiota Transplantation intervention 2: Psyllium Husk Powder
Intervention descriptions: intervention 1: The proposed intervention will deliver 250 milliliters of FMT by colonoscopy to the investigational FMT treatment groups at week 0. The placebo treatment group will instead receive the placebo FMT by colonoscopy at week 0 and then the investigational FMT by flexible sigmoidoscopy at week 8.

Investigational FMT is biologically active human fecal material that is pre-screened, tested, quarantined, stored, packaged, and labeled by OpenBiome. Placebo FMP250 is a control unit made of glycerol, saline, and food dye that is stored, packaged, and labeled identically to the investigational FMT, to ensure blinding during delivery. intervention 2: All subjects assigned to the fiber treatment arms will be required to take 1 teaspoon (approximately 5 grams) of psyllium husk powder twice a day (morning and night) for 8 weeks, beginning 3 days prior to Week 0 screening colonoscopy.

Psyllium husk powder is the dried and powdered form of a psyllium seed coat.

Protocol document:
ICF_001.pdf: 
 
 
  
 i 
 
IRB Protocol #: 19-04020045 
IND #: 19087 
NCT03998488 
INFORMED CONSENT FORM 
 
 
 
 
 
 
 
 
 
A randomized, placebo-controlled clinical trial examining the 
efficacy of Fecal Microbiota Transplantation (FMT) and 
subsequent dietary fiber in patients with moderate ulcerative 
Colitis  
 
 
 
 
 
Version Date: 10/13/2022 
 
 
 
 
 
 
 
 
 
Principal Investigator: 
Randy Longman, MD PhD 
Jill Roberts Center for IBD 
1283 York Avenue, 9th Flr 
New York, NY 10065 
P. (646)-962-6289 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 1 of 19 
 
WEILL CORNELL MEDICAL COLLEGE 
Informed Consent and HIPAA Authorization for Clinical Investigation 
 
 
Project Title: 
A randomized, placebo-controlled clinical trial examining the efficacy of 
Fecal Microbiota Transplantation (FMT) and subsequent dietary fiber in 
 patients with moderate ulcerative colitis 
IRB Protocol #: 
 19-04020045 
Principal 
Investigator: 
 Dr. Randy Longman 
Subject Name or 
number: 
  
MRN: 
  
Institution: 
 
Weill Cornell Medical College 
  
KEY INFORMATION ABOUT THIS RESEARCH STUDY 
We are asking you to choose whether to volunteer for a research study about mild to moderate Ulcerative 
Colitis (UC) disease response to human fecal microbiota transplantation (FMT) of the investigational study 
drug, FMP250, and the efficacy of the FMT if combined with supplemental psyllium fiber. Subjects will be 
randomized to the double-blinded, placebo-controlled study to determine whether they will receive FMP250 
or placebo first in an endoscopic procedure and if they are randomized to take supplemental psyllium fiber. 
Subjects will also provide blood, fecal and mucosal biopsy samples throughout the course of the study. This 
page is designed to give you key information to help you decide whether to participate. We have included 
detailed information after this page. Ask the research team questions. If you have questions later, the contact 
information for the research investigator in charge of the study is below.   
Purpose: What is the study about 
and how long will it last? 
The purpose of this interventional study is to gather information on the 
safety and effectiveness of the investigational drug, FMP250 when 
combined with supplemental psyllium fiber for patients with mild to 
moderate UC. For detailed descriptions, use the Consent Document.  
 
Your participation in this research will last about one year. 
Benefits: Key reasons you might 
choose to volunteer 
We cannot and do not guarantee that you will receive any benefits from 
this study. We hope the information learned from this study will benefit 
other patients with ulcerative colitis in the future. 
 
Risks: Key reasons you might 
choose NOT to volunteer 
The study is associated with risks to receiving the stool transplant, 
which is obtained from a donor. This can include fevers, abdominal 
cramping, bloody diarrhea, and serious blood-stream infections (rare). 
An additional risk of the stool transplant includes the transmission of 
various infectious organisms (bacterial, viral, fungal) contained in the 
stool. For a complete description of possible transmissible infectious 
organisms, refer to the Consent Document below. 
 
14-Feb-2023 -
14-Feb-2024


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 2 of 19 
 
If you are randomized to receive supplemental psyllium fiber, the main 
concern is the risk of choking. Rare side effects may include abdominal 
discomfort, nausea, mild abdominal cramps, griping, and faintness. 
 
Providing blood samples may cause discomfort, bleeding, bruising, and 
infection at the site of blood withdrawal (rare). Additional research 
biopsies pose the same risks as standard of care biopsies. These include 
small risk of bleeding and rare risk of infection. 
 
Due to the unknown risks of stool transplants to pregnant women, 
unborn babies, or nursing infants, you must not take part in this study if 
you are pregnant, plan to become pregnant during the research study 
period, or are breast-feeding a baby. For a complete description of risks, 
refer to the Consent Document below. 
Alternative treatments including standard medical therapy alone or 
surgery exist. For a complete description of alternate 
treatment/procedures, refer to the Consent Document below. 
Voluntary Participation: Do you 
have to take part in the study? 
Participation is optional. If you decide to take part in the study, it should 
be because you really want to volunteer. You will not lose any services, 
benefits or rights or access to you would normally have if you choose 
not to volunteer.  
What if you have questions, 
suggestions, or concerns? 
The person in charge of the study is Dr. Randy Longman [PI]. If you 
have questions, suggestions, or concerns regarding this study or you 
want to withdraw from the study his contact information is: 212-746-
5077. 
If you have any questions, suggestions or concerns about your rights as 
a volunteer in this research, contact staff in the Weill Cornell Medicine 
Institutional Review Board (IRB) between the business hours of 9am 
and 5pm EST, Monday-Friday at 646-962-8200 or send an e-mail to 
irb@med.cornell.edu.  
This overview does not include all the information you need to know before deciding whether to take 
part in the study. Much additional detail is given in the full consent document, which can be found on 
the pages that follow. Be sure to review the rest of this consent form before deciding about 
participation. 
INTRODUCTION 
You are invited to consider participating in a research study. You were selected as a possible participant in this 
study because you carry a diagnosis of ulcerative colitis and according to your medical provider have 
symptoms consistent with inadequately controlled disease. Please take your time to make your decision. It 
is important that you read and understand several general principles that apply to all who take part in our studies: 
a. Taking part in the study is entirely voluntary. 
 
b. Personal benefit to you may or may not result from taking part in the study, but knowledge gained from 
your participation may benefit others. 
 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 3 of 19 
 
c. You may decide not to participate in the study or you may decide to stop participating in the study at any 
time without loss of any benefits to which you are entitled. 
 
The purpose and nature of the study, possible benefits, risks, and discomforts, other options, your rights as a 
participant, and other information about the study are discussed below. Any new information discovered which 
might affect your decision to participate or remain in the study will be provided to you while you are a participant 
in this study. You are urged to ask any questions you have about this study with members of the research team. 
You should take whatever time you need to discuss the study with your physician and family. The decision to 
participate or not to participate is yours. If you decide to participate, please sign and date where indicated at the 
end of this form. 
The research study is being funded by Weill Cornell Medical College. Crohn’s Colitis Foundation and 
The National Institutes of Health (NIH) is providing a research grant for this study. Dr. Randy Longman 
is the primary investigator. 
 
The study will take place at facilities of New York Presbyterian Hospital where the investigators are 
members of the medical staff. New York-Presbyterian Hospital is neither a sponsor nor an investigator 
for this study. 
WHY IS THE STUDY BEING DONE? 
 
Ulcerative Colitis (UC) is a disease that causes diarrhea and lower abdominal pain. The current standard 
treatments for UC includes medicines that help to reduce the inflammation of your intestines or change 
your immune system, including steroids. Biologic therapies may also be used, but they work in different 
ways to also help reduce inflammation in your intestines. Although there are numerous medications 
available for the management of UC, patients commonly become steroid dependent and/or intolerant to 
medical management. 
 
Human fecal microbiota transplantation (FMT) is also known as a stool transplant and is an emerging 
treatment for UC, however, its clinical efficacy is variable. This is done by delivering the study drug, 
FMP250, by fecal transplantation (FMT) ideally at the ileum. This procedure is used to treat severe or 
chronic Clostridium difficile colitis and, in this case, it will be investigated in ulcerative colitis with the 
intention of introducing normal bacterial flora from a healthy donor to a diseased colon. 
 
The purpose of this study is to determine the efficacy of investigational FMT (FMP250) and to determine 
if the efficacy of FMT is increased when taken with supplemental psyllium fiber for patients with mild to 
moderate ulcerative colitis. 
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
Participants in the study are referred to as subjects. 
135 subjects will be recruited at this site. 
WHAT IS INVOLVED IN THE STUDY? 
This is a randomized, double-blind, placebo-controlled study done to test the role of supplemental 
psyllium fiber in the enhancement of efficacy of the investigational Fecal Microbiota Transplantation 
(FMT) done with the study drug, FMP250. 
 
If you decide to participate in this study, you will be “randomized” at a 1:1:1 ratio into one of the following 
3 research intervention groups provided all the inclusion and exclusion criteria are met: 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 4 of 19 
 
Group 1: Investigational FMT 
o Subject will receive investigational FMP250 once at day 0 colonoscopy 
o Subject will receive placebo FMP250 once at week 8 flexible sigmoidoscopy 
o Observed for 12 weeks 
 
Group 2: Investigational FMT + psyllium fiber 
o Subject will receive investigational FMP250 once at day 0 colonoscopy 
o Fiber supplementation of 1 teaspoon 2x/day (morning and night) for 8 weeks 
o Subject will receive placebo FMP250 once at week 8 flexible sigmoidoscopy 
o Observed for 12 weeks 
 
Group 3: Placebo FMT with or without psyllium fiber 
o Subject will receive placebo FMP250 once at day 0 colonoscopy 
o Half of subjects will be randomized to receive fiber supplementation of 1 teaspoon 
2x/day (morning and night) for 8 weeks 
o Subject will receive investigational 
FMP250 once at week 8 flexible 
sigmoidoscopy 
o Observed for 12 weeks 
Randomization means that you are put into a group by chance. It is like flipping a coin. Neither you, the research 
team, nor treating clinician will choose what group you will be in. You will have an equal chance of being 
placed in any group, 2 in 3 chances of receiving investigational FMT with a 1 in 3 chance of receiving 
placebo (which looks exactly like study drug but does not contain active ingredient). 
 
This is a blinded research study; therefore, neither you nor the clinician will know which research 
intervention will be given to you at the day 0 colonoscopy or week 8 flexible sigmoidoscopy. Blinding 
subjects and clinicians is done to ensure the results of the research are not influenced by anyone. It is 
important to note that even though you may be randomized to one of the research intervention groups 
receiving the study drug, the final eligibility criterion is determined by endoscopic evaluation during the 
day 0 colonoscopy. There is a chance that you may not receive the study drug at all if you do not meet this 
final endoscopic criterion. The randomized assignment will not be made known to you or the study 
physician until all week 8 evaluations have been completed for all study participants. Therefore, if you 
were blindly randomized to receive placebo at the day 0 colonoscopy, you will be given the investigational 
FMT (FMP250) during your week 8 flexible sigmoidoscopy and if you were blindly randomized to receive 
investigational FMT (FMP250) at the day 0 colonoscopy, you will be given the placebo FMT during your 
week 8 flexible sigmoidoscopy In the case of a medical emergency, the randomized intervention you 
received may be revealed by the study coordinator to the study doctor upon request. 
 
Please advise the researchers of any medications you are taking. In addition, if you are taking any over- 
the-counter drugs or herbal supplements, which you have obtained, from the drug store, grocery store, 
etc., you should advise the researchers. 
 
Study Procedures/Assessments 
 
You will have the following tests and procedures as a part of this research study: 
 
Study Procedures 
Screening 
Period 
Screening 
Colon- 
oscopy 
Phone 
Call 
Phone 
Call 
Clinic 
Visit 
Phone 
Call 
Clinic Visit Phone 
Call 
Clinic 
Visit 
Study Timeline 
Day 
-28 to -3 
Day 
0 
Day 
1 
Wk 
2 
Wk 
4 
Wk 
6 
Wk 
8 
Wk 
10 
Wk 
12 
Off 
Studyd 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 5 of 19 
 
Informed consent 
X 
Demographics 
X 
Medical history 
X 
Concurrent medication 
X 
X 
Intervention Randomization 
X 
Physical exam 
X 
X 
X 
X 
Vital signs + Height + Weight 
X 
X 
X 
X 
B-HCG (serum pregnancy 
test) (research purposes) 
X 
Urine Pregnancy Test (standard of 
care and research purposes) 
Xc 
X 
CRP: C-Reactive Protein 
(standard of care) 
X* 
X 
ESR: Erythrocyte 
Sedimentation Rate (standard of 
care) 
X* 
X 
CBCa (standard of care) 
X* 
X 
CMPb (standard of care) 
X* 
X 
Blood: HIV screen (standard of care) 
X* 
Blood: Hepatitis A B C Profile 
(standard of care) 
X* 
Blood: RPR (Treponema 
pallidum) (research purposes) 
X 
Blood: CMV IgM (standard of care) 
X* 
Blood: Quantiferon-TB (standard 
of care) 
X* 
Fecal Calprotectin (standard of care) 
X* 
X 
Stool: Ova &parasites (standard of 
care) 
X* 
Stool: Clostridium 
Difficile 
Toxin PCR (standard of care) 
X* 
Stool: Gastrointestinal 
Pathogen PCR Panele (standard of 
care) 
X* 
Screening Colonoscopy (standard 
of care) 
X 
Blinded (Investigational or 
Placebo) FMP250 Intervention 
X 
Follow-up Flex 
sigmoidoscopy (standard of care) 
X 
Blinded Investigational 
FMP250 at week 8 (research 
purposes) 
Placebo 
FMP250 group 
only 
Blinded Placebo FMP250 at 
Week 8 (research purposes) 
Investigational 
FMP250 group 
only 
Mucosal Biopsy Collection 
(research purposes) 
X 
X 
Blood and Stool Collection 
(research purposes) 
X ------- X 
X 
X 
X 
Follow-Up Phone calls (research 
purposes) 
X 
X 
X 
X 
X 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 6 of 19 
 
Diet Recall with Clinical 
Nutritionist or study MD 
(research purposes) 
X 
Psyllium Fiber Supplements 
(research purposes) 
X 
X 
Adverse event evaluation 
X 
X 
*: These standard of care laboratory tests are required to be conducted during the screening period. However if 
you consent below on page 5, this study may instead use recent laboratory results you had conducted within 
2 weeks of signing consent. 
a:  Complete Blood Count (WBC count, RBC count, Hb, Hct, platelet count) 
b: Comprehensive Metabolic Panel (glucose, calcium, sodium, potassium, CO2, chloride, BUN, Creatinine) 
c: Urine pregnancy test (women of childbearing potential) as standard of care for colonoscopy 
d: Off-study evaluation for the following year. 
e: Gastrointestinal Pathogen GI Panel (Campbylobacter species, Plesiomonas Shigelloides, Salmonella Species, 
Vibrio Species, Vibrio cholerae, Yersinia Enterocolitica, Enteroaggregative E. coli (EAEC), Enterpathogenic E. 
coli (EPEC), Enterotoxigenic E. coli (LT/ST), Shigalike toxin producing E.coli I (STX/ST2), Cryptosporidium, 
Cyclospora caretanensis, Entamoeba Cayetanensis, Giardia, Adenovirus F 40/41, Astrovirus, Norovirus GI/GII, 
Rotavirus A, Sapovirus, GID PCR INTERP) 
 
1. Screening Visit 
 
Once the informed consent document has been signed, the research study will be initiated by a screening 
visit. This is intended to ensure that you meet all criteria for this study. 
During this visit, the clinician will ask about your medication and medical history and will also conduct 
a physical exam. Additionally, you will meet with a registered dietician or your study physician during 
the screening period (days -28 to -3), either by an in-person or phone call consult, for research purposes 
to assess what you normally eat on a regular weekday by going through a 24-hour diet recall. 
 
Standard of care blood and stool testing will be conducted, if not done within 2 weeks of signing this 
consent form, in addition to a few other tests for research purposes to further determine eligibility. More 
details on these specific tests can be found in the Study Procedures/Assessments section. 
 
Please check “Yes” if you consent to having your recent blood and stool laboratory results 
to be used to determine your eligibility into this study. These laboratory tests must have 
been collected within 2 weeks of signing this consent form. If you check “No” you will be 
asked to do all standard of care blood and stool testing after signing this consent form. 
 
q Yes 
q No 
Once you have met all the eligibility criteria during the screening visit and the study clinician has 
reviewed your lab results, only then can you be randomized and evaluated at your upcoming standard 
of care colonoscopy. 
 
Evaluation of your disease severity during the colonoscopy is the final measure assessing your eligibility 
for this study. Your disease activity score will be evaluated during the colonoscopy and will determine 
if you are eligible to receive the active or placebo FMP250; there is a chance that you may not 
receive the study drug at all. 
If you do not meet the requirements to be included in this study, your clinician will explain why and 
should detail other appropriate therapeutic alternatives. 
 
2. Day 0 Colonoscopy and study drug administration 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 7 of 19 
 
 
You will undergo bowel prep and food fasting as of midnight of the procedure date, as you do for 
your usual standard of care colonoscopies with biopsies. 1-2 hours prior to the colonoscopy 
procedure, 
you 
will 
receive 
an 
anti-diarrheal 
agent(s) 
(e.g. 
loperamide 
and/or 
diphenoxylate/atropine) to help with the retention of the fecal transfer for research purposes. 
 
The colonoscopy will be performed in the NYP Endoscopy suite using standard of care practices, 
and you will be monitored post-procedure using standard practices. The study clinician will 
evaluate and score your disease activity to determine if you are eligible to receive the study drug. 
If you are eligible, you will blindly receive either the active or placebo FMP250 for research 
purposes based on your randomization. The fecal suspension will be delivered by 60cc syringes 
via the colonoscope to the deepest level of insertion (ideally the ileum). Therefore, up to 250cc of 
the fecal suspension will be administered in aliquots of 60cc. You will be asked to retain the fecal 
transfer for as long as possible, ideally greater than 4 hours. Your randomized intervention will 
not be made known to you or the medical provider conducting the procedure until after an 
evaluation by flexible sigmoidoscopy at week 8. 
 
Mucosal Biopsies for research 
A mucosal biopsy is the removal of a small piece, approximately the size of the tip of a pen, of 
your tissue from your intestine during an endoscopy procedure. Intestinal tissue biopsies may be 
tested to understand the effect of FMP250 and/or psyllium fiber, to predict who may respond to 
this intervention in the future, and to learn more about UC. 
During your colonoscopy, biopsies will be taken for diagnostic purposes. Additionally, 2 biopsies 
of the rectal tissue and 2 biopsies of the sigmoid tissue will be taken prior to the fecal microbiota 
transfer for research purposes. You will also undergo a flexible sigmoidoscopy with biopsies for 
standard of care at week 8. The same 4 biopsies from the rectal and sigmoid tissue will additionally 
be taken during this procedure for research purposes. 
 
Blood and Stool samples for research 
Collection 1: 
Prior to the day of your colonoscopy or if applicable, the initiation of psyllium husk, you 
will be asked to provide a pre-FMT stool sample for research purposes. You will also be 
asked to provide a blood sample and it will be drawn via venipuncture (the puncture of a 
vein with a needle to withdraw blood) and approximately 2.5 teaspoons of blood will be 
collected. 
 
Collection 2: 
You will be asked to provide a stool and blood sample on the day of your post-FMT week 
4 clinic visit. 
 
Collection 3: 
You will be asked to provide a stool and blood sample on the day of your post-FMT week 
8 clinic visit. 
 
Collection 4: 
You will be asked to provide a stool and blood sample on the day of your post-FMT week 
12 clinic visit. 
 
Pharmacodynamic blood testing 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 8 of 19 
 
Blood samples will also be drawn and used to test for certain proteins that may identify how your 
body is responding to the study drug, these proteins are called protein biomarkers. 
 
Pregnancy Testing 
If you are a female who can have children, you will provide a blood sample at the screening visit 
for research purposes, and then a urine sample for the colonoscopy as per standard of care protocol 
and at the week 8 clinic visit for research purposes to see if you are pregnant. A positive pregnancy 
result will disqualify you from being in the study. 
 
Stool Sample testing 
The standard of care stool samples taken at the screening visit will predominantly be tested to 
measure active gut inflammation and to ensure you do not have any intestinal viral or bacterial 
infections. Another stool sample will be collected at the week 8 clinic visit as standard of care to 
again test for active inflammation. All other stool samples collected throughout the course of the 
study are for research purposes. These will be immediately stored and eventually used to 
investigate the effect of FMT and/or psyllium fiber, to predict who may respond to this type of 
intervention in the future, and to learn more about UC. 
 
Follow-Up 
Phone Consults: 2, 4, 6 and10 weeks after the FMT 
o You will receive follow-up phone calls for evaluation of adverse effects and ulcerative 
colitis activity for research purposes. You will continue to receive follow-up phone calls 
every 6 months for the next year for research purposes. 
Importantly, you will follow up with your gastroenterologist as clinically indicated, and they will also ask 
you questions regarding your symptoms from the time of stool transplant, as well as perform further 
studies, as they feel is indicated by normal standards, such as colonoscopy, endoscopy, etc. 
 
HOW LONG WILL I BE IN THE STUDY? 
We think you will be in this study for a year. The research intervention visits along with clinical visits will occur 
over a 12-week period; however, you will receive follow up phone calls every 6 months for the following year 
so that we can evaluate how you respond to this therapy long-term. 
 
You can stop participating at any time. However, if you decide to stop participating in the study, we encourage 
you to talk to the researcher and your regular doctor first. There will be no consequences of sudden withdrawal 
from the study. If you choose to not participate in the study or to leave the study, your regular care will not be 
affected nor will your relations with WCMC, New York-Presbyterian Hospital, your physicians, or other 
personnel. In addition, you will not lose any of the benefits to which you are entitled. 
 
Withdrawal by investigator, physician, or sponsor 
The investigators, physicians or sponsors may stop the study or take you out of the study at any time 
should they judge that it is in your best interest to do so, if you experience a study-related injury, if you 
need additional or different medication, or if you do not comply with the study plan. They may remove 
you from the study for various other administrative and medical reasons. They can do this without your 
consent. 
 
WHAT ARE THE RISKS OF THE STUDY? 
For trials of drugs and procedures, there may be risks. These risks will be discussed with you by the 
research doctor. 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 9 of 19 
 
Risks and side effects related to the stool transplant we are studying include: Risks from donor stool, 
such as serious blood-stream infection (rare) or fevers, abdominal cramping, bloating, diarrhea, and 
bloody stool (less likely). Complications may include but are not limited to the following: 
a. Transmission of infectious organisms (bacterial, viral, fungal) contained in the stool 
a. Multi-Drug Resistant Organisms (MDROs) 
i. A potential risk of fecal microbiota transplantation (FMT) is the transmission of 
antibiotic-resistant bacteria. These are bacteria that are resistant to some antibiotics. 
These bacteria could be transmitted through FMT and could cause serious invasive 
infection or death. 
ii. The study drug, FMP250, that will be delivered by FMT is provided by 
OpenBiome, a universal stool bank where donors who provide stool for FMT 
undergo regular screening for certain antibiotic-resistant bacteria. Each FMT is 
only made available when these screens do not detect antibiotic-resistant bacteria 
in the donor before and after the stool donation. Donors also undergo regular 
clinical assessments for any risk factors associated with carrying antibiotic-resistant 
bacteria, such as recent use of antibiotics, visiting certain healthcare facilities, or 
certain travel activities. 
b. Shiga Toxin-Producing E. Coli (STEC) and Enteropathogenic E. Coli (EPEC) 
i. A potential risk of fecal microbiota transplantation (FMT) is the transmission of 
STEC and EPEC. STEC is a type of E. coli that can produce a toxin called Shiga 
toxin. Shiga toxin can be transmitted through FMT and can cause symptoms like 
abdominal pain, diarrhea (often bloody), vomiting, and mild fever. Most people 
develop symptoms within 3-4 days of acquiring the bacteria, and most get better 
within 5-7 days. EPEC is another type of E. coli that can be transmitted through 
FMT and is generally carried asymptomatically but can sometimes cause transient 
watery diarrhea, similar to traveler’s diarrhea. Symptoms typically resolve in a 
matter of days. 
ii. The study drug, FMP250, that will be delivered by FMT is provided by 
OpenBiome, a universal stool bank where donors who provide stool for FMT 
undergo regular screening for these bacteria. Each FMT is only made available to 
delivery when these stool screenings do not detect EPEC or STEC in the donor 
before and/or after the stool donation. 
c. SARS-CoV-2 Infection 
i. A potential risk of fecal microbiota transplantation (FMT) is the transmission of 
SARS-CoV-2, a novel coronavirus that causes the disease COVID-19. Infection 
with SARS-CoV-2 may be transmitted through stool and may cause serious illness 
or death. It is possible for healthy, asymptomatic stool donors to potentially be 
infected with SARS-CoV-2. 
ii. The FMT you will receive is provided by OpenBiome, a universal stool bank where 
donors who provide stool for FMT undergo regular stool, blood, and nasal 
screenings for many different infectious agents, including SARS-CoV-2, the virus 
that causes the illness called COVID-19. However, not all infectious agents are 
screened for and some infectious agents are as yet undiscovered. Each FMT unit is 
only made available for use when these screens do not detect the infectious agents 
for which we test. Donors also undergo regular in-person clinical assessments for 
any risk factors, including risk factors associated with carrying SARS-CoV-2, such 
as visiting certain healthcare facilities, or other behaviors that may increase the risk 
of exposure. However, because COVID-19 is so widespread, donors may be 
exposed or infected without having an identified risk factor for exposure. They may 
also have no symptoms of infection. OpenBiome continually updates its screening 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 10 of 19 
 
guidelines and procedures as additional data, tests, and information become 
available. 
iii.  If the FMT that you receive was made from stool donated after December 1st, 
2019, either the donor’s stool was tested for the presence of SARS-CoV-2 using a 
viral RNA test, or the stool donor was tested for the presence of SARS-CoV-2 using 
a nasopharyngeal swab at least every 14 days. Both kinds of test looks for the 
specific genetic material that makes up the virus. If a donor tests positive for SARS- 
CoV-2, OpenBiome destroys any FMT units made from that donor in the 4 weeks 
(28 days) before their positive test result. The donor is also disqualified from 
providing stool donations for at least 8 weeks. To be re-instated in the stool 
donation program after 8 weeks, the donor must pass all screens. 
iv. Although we cannot be absolutely certain, it is unlikely that SARS-CoV-2 is present 
in stool donations that were provided to OpenBiome on or prior to December 1st, 
2019. For this reason, testing on donors prior to December 1st has not been 
performed. 
v. Though these precautions are taken to minimize the risk of SARS-CoV-2 
transmission via FMT, the scientific and clinical community continues to learn 
more about SARS-CoV-2 and COVID-19. There are limits to the detection levels 
of laboratory tests, including those for SARS-CoV-2. Even with current screening 
and testing strategies, there may be additional risks that are unknown at this time. 
Although the donor screening tests we perform are likely to prevent you from 
receiving FMT from a donor who is infected with SARS-CoV-2, we cannot be 
absolutely certain that the stool you receive has not been contaminated with the 
SARS-CoV-2 virus. 
d. Monkeypox Infection 
i. A potential risk of fecal microbiota transplantation (FMT) is the transmission of 
monkeypox. Infection can cause symptoms including rash, fever, fatigue, 
myalgia, and respiratory symptoms which may be severe especially in 
immunocompromised patients. Studies have documented the presence of 
monkeypox virus DNA in rectal swabs and/or stool from infected individuals, but 
it is unknown whether monkeypox can be transmitted through stool or from 
asymptomatic infected individuals.
b. Missed polyps, cancer, or other lesion (infusing donor stool interferes with visualization of 
colonic mucosa) 
c. Allergic reaction to antigens in donor stool 
d. Enhanced ulcerative colitis activity 
e. Theoretical increased risk of developing disease which may be related to donor gut bacteria (i.e. 
obesity, metabolic syndrome, autoimmune conditions, allergic/atopic disorders, neurologic 
disorders, and/or malignancy) 
 
Risks from colonoscopy and sigmoidoscopy, such as perforation (serious but less likely), abdominal 
discomfort during or after the procedure (common but mild), and risks related to sedation (less likely). 
The incidence of risk associated with biopsies taken as standard of care does not increase with additional 
biopsies taken for research. These risks include bleeding, intestinal perforation, and / or infection. 
Bleeding associated with biopsy generally resolves spontaneously, however, in the unlikely event of 
persistent bleeding, clips and / or cautery can be applied to stop the bleeding. 
 
Risk from Medical Record Review: Subjects will be asked about their medical history, usage of birth 
control, concurrent medication. There is a risk associated with the loss of privacy or confidentiality due 
to the probing of information. For example, if your identity as a participant in this study or your 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 11 of 19 
 
identifiable health information were disclosed to unauthorized persons, there is the possible risk of 
discrimination by employers or insurance providers. 
Risk from Blood Draws: Drawing blood from a vein may cause local pain, bruising, occasional 
lightheadedness, fainting, and very rarely, infection at the site of the blood draw. Rarely, blood clots may 
form and infections may occur. If you feel faint, you should lie down right away to avoid falling down. 
You should let your study doctor or staff know if you have any of these problems. 
Risk from Placebo: In this research study, you may receive a placebo (inactive substance). If you 
receive the placebo, your condition may not change or may worsen. 
Risk from Psyllium Husk: The main concern with psyllium husk is the risk of choking, specifically if 
the product is not consumed with sufficient liquid. Our research physicians also hypothesize bloating may 
occur. The following rare side effects may be of concern for older adults: abdominal discomfort, nausea, 
mild abdominal cramps, griping, and faintness. 
Risk from Anti-Diarrheal Agents: Healthy adults usually don’t experience side effects from 
antidiarrheal medicines. But side effects may be a concern if you are older or have health problems. Side 
effects of diphenoxylate/atropine may include: drowsiness, dizziness, headache, tiredness, restlessness, 
blurred vision, dry mouth, nausea, vomiting, upset stomach, loss of appetite, skin rash, or itching. Unlikely 
but serious side effects of diphenoxylate/atropine including: stomach or abdominal pain or swelling, 
severe nausea or vomiting, mental/mood changes (e.g., confusion, depression), or numbness and tingling 
of arms or legs. Side effects of loperamide may include: dizziness, drowsiness, tiredness, constipation, 
stomach pain, skin rash, or itching. Unlikely but serious side effects may also include severe 
constipation/nausea/vomiting, stomach or abdominal pain, or uncomfortable fullness of the stomach or 
abdomen. 
Risks for Women of Child-Bearing Potential: Participation in this the study may involve unknown risks 
to a pregnant woman, unborn baby or nursing infant. You must not take part in this study if you are 
pregnant, plan to become pregnant during the research study period, or are breast-feeding a baby. 
 
What do I need to know about reproductive health and/or sexual activity if I am in this study? 
If you are sexually active, you should use at least one effective means of birth control while 
participating in this research study. According to the World Health Organization and the United 
States Center for Disease Control and Prevention, the most effective forms of birth control include 
complete abstinence, surgical sterilization (both male and female), intrauterine devices (IUDs), 
and the contraceptive implant. The next most effective forms of birth control include injectables, 
oral contraceptive pills, the contraceptive ring, or the contraceptive patch. Acceptable, but least 
effective, methods of birth control include male condoms (with or without spermicide) and female 
condoms. 
If you become pregnant while participating in this research study, it is important that you 
tell the study doctor or other research team member immediately. You will be required to stop 
receiving procedures and blinded FMT interventions for this study; however, other clinical care 
options will be discussed with you at that time if necessary and you will continue to complete the 
AE phone calls, week 4 clinic visit, and week 12 clinic visit as originally planned. The only 
difference will be that your week 8 assessment will be changed from a standard of care flexible 
sigmoidoscopy procedure into a clinic visit. This means you will do all other assessments, such as 
standard of care labs, research collection of blood and stool, physical exam, vital signs, height and 
weight measurements, etc. Therefore, the week 8 will no longer include a procedure, FMT blinded 
treatment, and biopsy collection for research. 
If you are considered to be postmenopausal, you are not required to use contraception while 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 12 of 19 
 
participating in this research study. Postmenopausal women rarely become pregnant. 
There may also be side effects, other than listed above that we cannot predict. Other drugs may be given 
to make side effects that occur less serious and less uncomfortable. Many side effects go away shortly 
after the stool transplant is stopped, but in some cases side effects can be serious, long lasting or permanent 
For more information about risks and side effects, ask the researcher or contact Dr. Randy Longman at 
212-746- 5077. 
 
ARE THERE ANY BENEFITS TO TAKING PART IN THE STUDY? 
We cannot and do not guarantee that you will receive any benefits from this study. We hope the information 
learned from this study will benefit other patients with ulcerative colitis in the future. 
 
WHAT OTHER OPTIONS ARE THERE? 
Instead of being in this study, you have these options: 
- 
You may choose not to participate in this study 
- 
You may choose to take standard medical therapy alone (for example, topical 5-ASA medications or 
topical steroids, oral steroids, immune modulators, and anti-TNF medications) or even surgery 
depending on what is recommended by your primary gastroenterologist. 
 
WHAT ABOUT CONFIDENTIALITY? 
Efforts will be made to protect your medical records and other personal information to the extent allowed by 
law. However, we cannot guarantee absolute confidentiality. Records of study participants are stored and kept 
according to legal requirements and may be part of your medical record. You will not be identified personally 
in any reports or publications resulting from this study. Organizations that may request to inspect and/or copy 
your research and medical records for quality assurance and data analysis include groups such as: 
o Weill Cornell Medical College and New York-Presbyterian Hospital 
o The Institutional Review Board (IRB) 
o The Office of Human Research Protection (OHRP) 
o Department of Health and Human Services and National Institutes of Health 
o The Food and Drug Administration (FDA) and/or their representatives 
By signing this consent form, you authorize access to this confidential information. You also authorize 
the release of your medical records to Weill Cornell Medical College and New York-Presbyterian Hospital 
by any other hospitals or institutions where you might receive medical care of any kind while you are 
participating in this study. 
 
If information about your participation in this study is stored in a computer, we will take the following 
precautions to protect it from unauthorized disclosure, tampering, or damage by requiring a unique ID and 
password to log into the database: All tissue, blood, or stool samples will be labeled with a unique 
alphanumeric identifier that does not link the specimen to the subject or the subjects’ demographics. The 
samples are physically hand delivered to Dr. Longman’s lab at WCMC by the PI and/or the research team. 
Identifiable samples are not sent to Dr. Longman’s lab. A password protected database file will be 
maintained that links the samples with the subject. Only the study investigators will have access to this 
file. It will be stored in a password protected computer in a locked office. In addition, only personnel who 
are associated with the study will have access to the study specific records in the database. 
 
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. 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 13 of 19 
 
 
Genetic Information Nondiscrimination Act (GINA) 
 
To the extent permitted by law, under no circumstances will any information linking you to specific test 
results be disclosed to any individual or organization without your written consent. A Federal law, called the 
Genetic Information Nondiscrimination Act (GINA), generally makes it illegal for health insurance 
companies, health plans, and most employers to discriminate against you based on your genetic information. 
This law generally will protect you in the following ways: 
 
• Health insurance companies and group health plans may not request your genetic information that we 
get from this research. 
• Health insurance companies and group health plans may not use your genetic information when 
making decisions regarding your eligibility or premiums. 
• Employers with 15 or more employees may not use your genetic information that we get from this 
research when making a decision to hire, promote, or fire you or when setting the terms of your 
employment. 
 
Be aware that this new Federal law does not protect you against genetic discrimination by companies that sell 
life insurance, disability insurance, or long-term care insurance. Nor does this Federal law prohibit 
discrimination on the basis of an already manifest genetic disease or disorder. 
 
 
HIPAA AUTHORIZATION TO USE/DISCLOSE PROTECTED HEALTH INFORMATION FOR 
RESEARCH 
 
Purposes for Using or Sharing Protected Health Information: If you decide to join this study, WCMC 
researchers need your permission to use your protected health information. If you give permission, Weill 
Cornell Medical College (WCMC) and/or New York-Presbyterian Hospital (NYPH) researchers may use 
your information or share (disclose) information about you for their research that is considered to be 
protected health information. 
 
Voluntary Choice: The choice to give WCMC and/or NYPH researcher’s permission to use or share your 
protected health information for their research is voluntary. It is completely up to you. No one can force 
you to give permission. However, you must give permission for WCMC and/or NYPH researchers to use 
or share your protected health information if you want to participate in the study. If you decline to sign this 
form, you cannot participate in this study, because the researchers will not be able to obtain and/or use the 
information they need in order to conduct their research. Refusing to give permission will not affect your 
ability to get usual treatment, or health care from WCMC and/or NYPH. 
 
Protected Health Information To Be Used or Shared: Government rules require that researchers get 
your permission (authorization) to use or share your protected health information. Your medical 
information may be disclosed to authorized public health or government officials for public health 
activities when required or authorized by law. If you give permission, the researchers could use or share 
with the entities identified above any protected health information related to this research study from your 
medical records and from any test results, which includes HIV testing, hepatitis testing, additional blood 
tests (RPR, CMV IgM antibody, ESR, CRP), stool studies (routine stool culture for enteric GI pathogens: 
E. coli, Salmonella, Shigella, Yersinia, Campylobacter, Cryptosporidium, Giardia, Vibrio, H. pylori, 
Plesiomonas Shigelloides, Cylospora, Entamoeba, Adenovirus, Astrovirus, Norovirus, Rotavirus, 
Sapovirus), Ova and parasites, Clostridium difficile toxin by PCR, urine pregnancy test, colonic biopsies 
during colonoscopy, genetic testing (genetic sequencing of bacteria) from research only stool and biopsy 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 14 of 19 
 
specimens, and immune cells taken from blood research samples. 
 
Other Use and Sharing of Protected Health Information: If you give permission, the researchers could 
also use your protected health information to develop new procedures or commercial products. They could 
share your protected health information with the study sponsor the WCMC Institutional Review Board, 
inspectors who check the research, government agencies and research study staff. 
 
The information that may be shared with the sponsor and/or government agencies could include your 
medical record and your research record related to this study. They may not be considered covered 
entities under the Privacy Rule and your information would not be subject to protections under the 
Privacy Rule. 
 
RESEARCH REPOSITORY 
 
What is a Research Repository? 
 
A research repository (database) is a collection of information from the health and medical records of many 
individuals and can sometimes include identifiable specimens (like your tissue). The repository (database) 
may share the information with researchers who study medical conditions and diseases. 
 
The repository (database) includes codes that identify each person whose information is collected. 
However, the repository does not share information with researchers unless the researchers promise to 
keep the information confidential. 
 
RESEARCH PARTICIPANT: Please check the box below that describe your wishes. : 
The WCMC Repository may keep my protected health information and/or specimens and share it 
with qualified researchers studying the research described above. If information goes to an outside 
entity then the Privacy Rule may not apply. 
 
The WCMC Repository may keep my protected health information and/or specimens and share it 
with qualified researchers studying the research described above AND for unspecified research to 
be done in the future. I understand that the samples will be stored for 20 years and will be destroyed 
after the research is completed. If information goes to an outside entity then the Privacy Rule may 
not apply. 
The WCMC Repository may not keep my protected health information for a research repository. 
 
By signing this consent form, you agree to give these samples to WCMC for research purposes. 
 
CANCELING AUTHORIZATION 
Canceling Permission: If you give the WCMC and/or NYPH researchers permission to use or share 
your protected health information, you have the right to cancel your permission whenever you want. 
However, canceling your permission will not apply to information that the researchers have already used 
or shared. 
If you wish to cancel your permission, you may do so at any time by writing to: 
Privacy Officer 
1300 York Avenue, Box 303 
New York, NY 10065 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 15 of 19 
 
 
If you have questions about this, call (646) 962-6930 or e-mail: privacy@med.cornell.edu 
 
End of Permission: Unless you cancel it, permission for WCMC and/or NYPH researchers to use or share 
your protected health information for their research will never end. 
 
ACCESS TO RESEARCH RECORDS 
During the course of this study, you will not have access to see or copy specific sections of your 
protected health information that contains research information as described in this authorization form, in 
accordance with Weill Cornell Medical College (WCMC) and/or New York-Presbyterian Hospital 
(NYPH) policies. This is done to prevent knowledge of study results affecting the reliability of the study. 
The part of your private information that you will not have access to is: which arm of the study you are 
randomized to or any other information that is “blinded” (that is, kept secret during the study to prevent 
bias). Your information will be available should an emergency arise that would require the treating 
physician to know this information in order to best treat you. Your right to access this information will be 
reinstated after the completion of your week 8 visit. If you wish to appeal this temporary suspension at 
any time, please write to the Privacy officer at the address provided on this form. By signing this form, 
you are agreeing to this temporary suspension of your rights to assess protected health information. 
 
CERTIFICATE OF CONFIDENTIALITY 
A Certificate of Confidentiality has been granted by the Department of Health and Human Services 
(DHHS). This Certificate will protect the investigators (research/study staff) from being forced to 
release any research data in which the subject is identified even under a court order or subpoena. This 
protection is not absolute. For instance, it does not override any state requirement to report child abuse 
to the appropriate authorities. 
 
WHAT ARE THE COSTS? 
The study will pay for any related procedures that are not considered standard care for patients with your 
disease. You will not have to pay for the study drug (fecal microbiota transplantation), psyllium dietary 
supplements, blood and stool sample collection for research purposes, or the loperamide and/or 
diphenoxylate/atropine provided for stool retention at the day 0 colonoscopy. These services will be 
provided for research purposes by Weill Cornell Medicine at no cost. 
The physical examinations, standard laboratory tests, and diagnostic procedures, such as the colonoscopy 
and flexible sigmoidoscopy, are considered part of the standard care for patients with your disease who 
have had a change in clinical symptoms. The costs associated with each test will be charged to you or your 
insurance provider in the same manner as if you were not part of this research study. You or your insurance 
company will be charged for continuing medical care and/or hospitalization that are not a part of the study. 
The costs of all of the other medications and the administration of these medications that you receive 
during this study will be charged to you or your insurance provider. If unsuspected, incidental findings 
are noted during blood or stool testing or during colonoscopy and further medical tests and/or treatments 
are considered, such tests and/or treatments are no longer considered part of the study and therefore would 
be billed to you or your insurer. You should expect no compensation or reimbursement for these costs or 
any risks and anxieties associated with any such follow up care. Therefore, you or your insurance provider 
will need to assume responsibility for these costs. You will be billed for all costs or co-payments that are 
not paid by your insurance provider. 
 
Taking part in this study may lead to added costs for you or your insurance company. Please ask about 
any expected added costs or potential insurance problems. You may wish to consult with your insurance 
company in advance about whether insurance will pay for these costs. 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 16 of 19 
 
 
POLICY/PROCEDURES FOR RESEARCH RELATED INJURY 
The Policy and Procedure for Weill Cornell Medical College are as follows: 
We are obligated to inform you about WCMC’s policy in the event injury occurs. If, as a result of your 
participation, you experience injury from known or unknown risks of the research procedures as described, 
immediate medical care and treatment, including hospitalization, if necessary, will be available at the usual 
charge for such treatment. No monetary compensation is available from WCMC or New York-Presbyterian 
Hospital. Further information can be obtained by calling the Institutional Review Board at (646) 962-8200. 
 
COMPENSATION FOR PARTICIPATION 
You will not receive compensation for participating in this study. You should not expect anyone to pay you for 
pain, worry, lost income, or non-medical care costs that occur from taking part in this research study. 
 
COMMERCIAL INTEREST 
Materials or data obtained from you in this research may be used for educational or commercial purposes. 
It is the policy of WCMC, New York-Presbyterian Hospital not to provide financial compensation to you 
should this occur. 
 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
Taking part in this study is voluntary. You may choose to not take part in the study or to leave the study at any 
time. If you choose to not participate in the study or to leave the study, your regular care will not be affected nor 
will your relations with the Weill Cornell Medical College, New York-Presbyterian Hospital, your physicians, 
or other personnel. In addition, you will not lose any of the benefits to which you are entitled. 
A Data Safety and Monitoring Board, an independent group of experts, will be reviewing the data from this 
research throughout the study. We will tell you about new information that may affect your health, welfare, or 
participation in this study. 
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
For questions about the study, a research-related injury, any problems, unexpected physical or psychological 
discomforts, or if you think that something unusual or unexpected is happening, call Dr. Randy Longman at 
212- 746-5077 or the Department of Gastroenterology. Be sure to inform the physician of your 
participation in this study. 
If you have questions about your rights as a research participant, contact the WCMC IRB Office. 
Direct your questions to: 
Institutional Review Board 
Address: 1300 York Avenue, Box 89, New York, New York 10065 
Telephone: (646) 962-8200 
 
 
Consent for Research Study 
 
Project Title: A randomized, placebo-controlled clinical trial examining the efficacy of Fecal Microbiota 
Transplantation (FMT) and subsequent dietary fiber in patients with moderate ulcerative colitis 
 
Principal Investigator: Dr. Randy Longman, MD PhD 
 
RESEARCHER’S STATEMENT 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 17 of 19 
 
I have fully explained this study to the subject. As a representative of this study, I have explained the purpose, 
the procedures, the benefits and risks that are involved in this research study. Any questions that have been 
raised have been answered to the individual’s satisfaction. 
 
 
Signature of person obtaining the consent 
Print Name of Person 
Date 
(Principal Investigator or Co-investigator) 
 
SUBJECT’S STATEMENT 
 
I. 
I 
 (patient name) authorize the performance of fecal 
transplantation (stool transplant) procedure to be performed by Dr. Randy Longman, M.D Ph.D., and 
his assistants or designees. 
 
II. 
I understand that fecal transplantation may be performed through colonoscopy, but fecal transplant is 
neither intended nor adequate to screen for colorectal cancer. Instead, fecal transplantation is a 
procedure that has been used to treat severe or chronic Clostridium difficile colitis and in my case its 
use will be investigated in ulcerative colitis by introducing normal bacterial flora from a healthy donor 
to the diseased colon. 
 
III. 
I also acknowledge that residents and assistants designated by my physician may participate in the 
procedure and there may be other observers or vendors present. 
 
IV. 
I, the undersigned, have been informed about this study’s purpose, procedures, possible benefits and 
risks, and I have received a copy of this consent. I understand that donors are screened and undergo 
testing for many common communicable diseases to ensure that the procedure is done as safely as 
possible, but that it is not possible to test donors for all possible organisms and some infections may 
be undetectable. I understand that a solution of donor stool is infused into the colon. The alternative 
treatment(s), including antibiotics, 5-ASAs, immune-modulators, steroids, surgery, or no treatment at 
all and the risks and benefits of those alterative treatment(s) have been explained to me and I 
understand that my condition could worsen, improve or stay the same with fecal transplant or any 
other alternative treatments. Patients critically ill with ulcerative colitis, have a risk of dying from this 
condition regardless of what treatment is used and fecal transplant may not be successful. The risks 
related to the use of colonoscopy and sigmoidoscopy have been explained, and I have signed a form 
entitled, “Acknowledgement of Consent for Surgical or Other Procedure.” 
 
V. 
The risks of a fecal transplantation procedure have been discussed with me. I understand that 
complications may arise as a result of a fecal transplant. Complications may include but are not limited 
to the following: 
a. Transmission of infectious organisms (bacterial, viral, fungal) contained in the stool 
b. Missed polyps, cancer, or other lesion (infusing donor stool interferes with visualization of 
colonic mucosa) 
c. Allergic reaction to antigens in donor stool 
d. Enhanced ulcerative colitis activity 
e. Theoretical increased risk of developing disease which may be related to donor gut bacteria 
(i.e. obesity, metabolic syndrome, autoimmune conditions, allergic/atopic disorders, 
neurologic disorders, and/or malignancy) 
 
VI. 
I understand that this is NOT a complete list, and that unforeseen risks do exist which may not have 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 18 of 19 
 
been discussed with me. 
 
VII. 
I understand that the above, as well as other complications, sometimes require additional procedures 
or operations and they have been discussed with me. I consent to such additional procedures which 
my physician deems necessary. 
 
VIII. 
I hereby consent to the taking of photographs, videotapes, and/or illustrations of my operation and 
other medical procedures for clinical purposes. 
 
IX. 
I, the undersigned, have been informed about this study’s purpose, procedures, possible benefits and risks, 
and I have received a copy of this consent. I have been given the opportunity to ask questions before I sign, 
and I have been told that I can ask other questions at any time. I voluntarily agree to participate in this study. 
I am free to withdraw from the study at any time without need to justify my decision. This withdrawal will 
not in any way affect my future treatment or medical management and I will not lose any benefits to which 
I otherwise am entitled. I agree to cooperate with Randy Longman, M.D. Ph.D. and the research staff to 
inform them immediately if I experience any unexpected or unusual symptoms. 
 
 
 
Signature of Subject 
Print Name of Subject 
Date 
 
OPTIONAL GENETIC TESTING 
 
In addition to the study, you have the option to allow further experimental studies with your samples as 
explained below. Your participation is optional and you do not have to agree to participate in the additional 
studies in order to participate in the main study. 
 
Blood, stool, and tissue samples obtained for research purposes throughout the study may be used to 
perform genetic tests (tests on cells which look for changes in your genetic makeup, like DNA or RNA). 
These tests will not tell if your UC is inherited and will not involve members of your family. 
 
The researchers will study how changes in cells’ genetic information might affect the disease’s response 
to study treatment and the course of disease. 
 
The test results may not be helpful to you at this time and are research-grade only. However, this data may 
make it possible to better understand UC and other diseases and for the potential development of 
companion diagnostics and to know how to diagnose and treat UC in the future. This knowledge may also 
be useful for future clinical studies. 
 
The samples will be retained at the study site or at a secure storage facility in case there is a need to re- 
test them. The samples will be destroyed within twenty years after the end of the trial or earlier if required 
by law. If you decide to withdraw your consent, you can request that all retained identifiable samples be 
removed from any future genetic testing. If you make this decision, you must notify the study doctor in 
writing. 
 
The results of the tests may not be available to you via your doctor because the tests are research-grade 
only and may not have been done by the end of your study duration. These results must not be used to 


WEILL CORNELL MEDICAL COLLEGE 
IRB Protocol #19-04020045 
Consent version date: 
10/13/2022 
Page 19 of 19 
 
diagnose your disease and/or make treatment decisions. 
 
o I have read this informed consent and AGREE to participate in the optional genetic testing. 
 
o I have read this informed consent and DO NOT WISH to participate in the optional genetic testing. 
 
 
 
 
Research Subject’s Name (Print ) 
 
 
 
Research Subject’s Signature 
Date of Signature 

Prot_SAP_002.pdf: 
 
 
  
 i 
 
IRB Protocol #: 19-04020045 
IND #: 19087 
NCT03998488 
PROTOCOL 
 
 
 
 
 
 
 
 
A randomized, placebo-controlled clinical trial examining the 
efficacy of Fecal Microbiota Transplantation (FMT) and 
subsequent dietary fiber in patients with moderate ulcerative 
Colitis  
 
 
 
 
 
Version Date: 11/13/2024 
 
 
 
 
 
 
 
 
 
Principal Investigator: 
Randy Longman, MD PhD 
Jill Roberts Center for IBD 
1283 York Avenue, 9th Flr 
New York, NY 10065 
P. (646)-962-6289 
E. ral2006@med.cornell.edu 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
ii 
 
Co-Investigators: 
 
 
 
 
 
Carl Crawford, MD 
 
Ellen Scherl, MD 
 
The Division of Gastroenterology & Hepatology 
 
Jill Roberts Center for IBD 
 
1305 York Avenue, 4th or 9th Flr 
 
1283 York Avenue, 9th Flr 
 
New York, NY 10021 
 
New York, NY 10065 
 
P. (646)-962-4000 
 
P. (212)-746-5077 
 
E. cvc9002@med.cornell.edu 
 
E. ejs2005@med.cornell.edu 
 
 
 
 
Dana Lukin, MD PhD 
 
Rachel Niec, MD PhD 
 
Jill Roberts Center for IBD 
  
Jill Roberts Center for IBD 
 
1283 York Avenue, 9th Flr 
 
1283 York Avenue, 9th Flr 
 
New York, NY 10065 
 
New York, NY 10065 
 
P. (212)-746-5077 
 
P. (212)-746-5077 
E. djl9010@med.cornell.edu 
 
E. ran2006@med.cornell.edu 
 
 
 
 
 
 
Statistician: 
 
 
Clinical Nutritionist: 
 
Paul J. Christos, DrPH, MS 
 
Ryan Warren, MS, RDN, CDN 
 
Department of Biostatistics and Epidemiology 
 
Jill Roberts Center for IBD 
 
402 East 67th Street, Room 241 
 
1283 York Avenue, 9th Flr 
 
New York NY 10021 
 
New York, NY 10065 
 
P. 646-962-8018 
 
P: 212-746-5077 
 
F: 646-962-0281 
 
E. ryw2002@med.cornell.edu 
 
E. pac2001@med.cornell.edu 
 
 
 
Study Coordinators: 
 
 
 
 
Nancy Tran 
 
Alexa Lavergne  
 
Jill Roberts Center for IBD 
 
Jill Roberts Center for IBD  
 
1283 York Avenue, 9th Flr 
 
1283 York Avenue, 9th Flr  
 
New York, NY 10065 
 
New York, NY 10065 
 
P. (646)-697-0985 
 
P. (646)-697-0985  
 
E. nat4010@med.cornell.edu 
 
E. all4022@med.cornell.edu 
 
 
 
Benjamin Pundyk 
 
Jill Roberts Center for IBD 
 
1283 York Avenue, 9th Flr 
 
New York, NY 10065 
 
P. (646)-697-0985 
 
E. bep4002@med.cornell.edu 
 
 
 
 
Participating Sites:   
  Study Enrollment and Treatment                                   Sample Processing and Data Analysis 
                      
 
The Jill Roberts Center for IBD 
The Jill Roberts Institute for Research in IBD 
 
Gastroenterology and Hepatology at DHK 
Belfer Research Building, 7th Flr 
 
Weill Cornell Medical Center / NYP Hospital 
413 E 69th Street 
 
1283 York Avenue, 9th Flr 
New York, NY 10021 
 
New York, NY 10065 
 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
iii 
 
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................ VIII 
CONFIDENTIALITY STATEMENT .......................................................................................... VIII 
LIST OF ABBREVIATIONS ...................................................................................................... IX 
1. PROTOCOL SUMMARY ....................................................................................................... 1 
1.1 
Study Schematic ......................................................................................................... 3 
1.2 
Study Objectives ........................................................................................................ 4 
1.2.1  
Primary Objective ................................................................................................ 4 
1.2.2  
Secondary Objective(s) ........................................................................................ 4 
1.2.3  
Exploratory Objective(s) ...................................................................................... 4 
2. BACKGROUND ................................................................................................................... 4 
2.1 
Ulcerative Colitis ........................................................................................................ 4 
2.2 
Fecal Microbiota Transplant (FMT) ............................................................................. 5 
2.3 
Dietary Fiber Supplementation ................................................................................... 6 
2.4 
Rationale ................................................................................................................... 7 
2.4.1 
FMP Lower Delivery Microbiota Transplant (FMP250) .......................................... 7 
2.4.2 
Psyllium Husk Powder ......................................................................................... 7 
2.5 
 Risk/Benefit Assessment ........................................................................................... 8 
2.5.1 
Known Potential Risks ......................................................................................... 8 
2.5.1.1.  FMT-related: (adapted from OpenBiome FMP250 Investigator Brochure): ........... 8 
2.5.1.2.  Psyllium-related .................................................................................................. 9 
2.5.2 
Known Potential Benefits .................................................................................... 9 
2.5.2.1.  FMT-related ........................................................................................................ 9 
2.5.2.2.  Psyllium-related .................................................................................................. 9 
2.5.3 
Assessment of Potential Risks and Benefits .......................................................... 9 
2.6 
Correlative Studies Background ................................................................................ 10 
3. STUDY DESIGN ................................................................................................................. 10 
3.1 
Overall Design .......................................................................................................... 10 
3.2 
Scientific Rationale for Study Design ......................................................................... 11 
3.3 
Justification for Dose ................................................................................................ 12 
3.4 
End of Study Definition ............................................................................................ 12 
4. SUBJECT SELECTION ......................................................................................................... 12 
4.1 
Study Population...................................................................................................... 12 
4.2 
Inclusion Criteria ...................................................................................................... 12 
4.3 
Exclusion Criteria ..................................................................................................... 14 
4.4 
Lifestyle Considerations ........................................................................................... 14 
4.5 
Screen Failures ......................................................................................................... 14 
4.6 
Strategies for Recruitment and Retention ................................................................. 14 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
iv 
 
5. REGISTRATION PROCEDURES ........................................................................................... 15 
5.1 
Subject Registration (WCM only) .............................................................................. 15 
5.2 Subject Registration (Sub-sites) .................................................................................... 15 
6. STUDY PROCEDURES ........................................................................................................ 15 
6.1 
Schedule of Assessments .......................................................................................... 15 
6.1.1 
Screening Visit (Days -28 to -3) .......................................................................... 17 
6.1.2 
Treatment Phase ............................................................................................... 18 
6.1.2.1 
Screening Colonoscopy (Baseline, Week 0 Day 0) ............................................ 18 
6.1.2.2 
Clinic Visit 3 (Week 8 ± 5 day(s)) ..................................................................... 19 
6.1.3 
Follow-up Phase ................................................................................................ 19 
6.1.3.1 
Phone Consults .............................................................................................. 19 
6.1.3.2 
Clinic Visits..................................................................................................... 19 
6.1.4 
COVID-19 Study Modifications ........................................................................... 19 
7. STUDY INTERVENTION ..................................................................................................... 20 
7.1 
Study Intervention/Device Description ..................................................................... 20 
7.1.1 
Investigational and Placebo FMP250 ..................................................................... 20 
7.1.2 
Psyllium Husk Powder........................................................................................... 20 
7.2 
Availability ............................................................................................................... 20 
7.3 
Acquisition and Accountability ................................................................................. 20 
7.4 
Formulation, Appearance, Packaging, and Labeling ................................................... 21 
7.4.1 
Investigational FMP250 Formulation and Appearance ........................................... 21 
7.4.2 
Placebo FMP250 Formulation and Appearance ...................................................... 21 
7.4.3 
Psyllium Husk Powder, Organic Formulation and Appearance ............................... 21 
7.4.3 
Manufacturing Addresses ..................................................................................... 21 
7.4.4 
Product Labeling and Documentation ................................................................... 22 
7.5 
Product Packaging and Handling ............................................................................... 22 
7.6 
Product Storage and Stability ................................................................................... 23 
7.7 
Product Preparation ................................................................................................. 23 
7.8 
Dosing and Administration ....................................................................................... 24 
7.8.1 
FMP250 ................................................................................................................ 24 
7.8.2 
Psyllium ................................................................................................................ 24 
7.8.3 
Dosing Delays/Dose Modifications..................................................................... 24 
7.9 
General Concomitant Medication and Supportive Care Guidelines ............................ 24 
7.10 Duration of Therapy and Criteria for Removal from Study ........................................... 24 
7.11 Duration of Follow Up ................................................................................................ 25 
7.12 Measures to Minimize Bias: Randomization and Blinding ............................................ 25 
7.13 Study Intervention/Follow-up Compliance .................................................................. 26 
8. STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...................................................................................... 26 
8.1 
Discontinuation of Study Intervention ...................................................................... 26 
8.2 
Participant Discontinuation/Withdrawal from the Study .......................................... 27 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
v 
 
8.3 
Lost to Follow Up ..................................................................................................... 27 
9. CORRELATIVE/SPECIAL STUDIES ....................................................................................... 28 
9.1 
Laboratory Correlative Studies ................................................................................. 28 
9.1.1 
Microbiome – Laboratory Correlative Study #1 .................................................. 28 
9.1.1.1 
Collection of Specimen(s):  Fecal ..................................................................... 28 
9.1.1.2 
Handling of Specimen(s): Frozen -80C ............................................................. 28 
9.1.2 
Lamina propria cells – Laboratory Correlative Study #2 ...................................... 28 
9.1.2.1 
Collection of Specimen(s):  Biopsy .................................................................. 28 
9.1.2.2 
Handling of Specimen(s): Collected in PBS, Processed in Longman lab ............. 28 
9.1.3 
Peripheral Blood – Laboratory Correlative Study #3 ........................................... 28 
9.1.3.1 
Collection of Specimen(s):  Blood sample ....................................................... 28 
9.1.3.2 
Handling of Specimen(s): Processed in Longman lab ....................................... 28 
9.2 
Special Studies ......................................................................................................... 28 
9.2.1 
Special Correlative Study #1 .............................................................................. 28 
9.2.1.1 
Assessment .................................................................................................... 28 
9.2.2 
Special Correlative Study #2 .............................................................................. 28 
9.2.2.1 
Assessment .................................................................................................... 28 
10.  MEASUREMENT OF EFFECT ............................................................................................ 29 
10.1 Response Criteria ....................................................................................................... 29 
10.1.1 Primary Endpoint Assessments ................................................................................ 29 
10.1.1.1 Mayo Scoring System30 ......................................................................................... 29 
10.1.2 Secondary Endpoint Assessments ............................................................................ 30 
10.1.2.1 Biomarkers ........................................................................................................... 30 
10.1.2.2 Adverse Event Reporting ....................................................................................... 30 
10.2 Duration of Response ................................................................................................. 30 
10.3 Progression-Free Survival ........................................................................................... 30 
10.4 Other Response Parameters ....................................................................................... 30 
11. DATA REPORTING / REGULATORY CONSIDERATIONS ...................................................... 30 
11.1 Data Collection ........................................................................................................... 31 
11.1.1 REDCap ................................................................................................................ 31 
11.2 Regulatory Considerations .......................................................................................... 31 
11.2.1 Institutional Review Board/Ethics Committee Approval ........................................ 31 
11.2.2 Ethical Conduct of the Study ................................................................................ 32 
11.2.3 Informed Consent ................................................................................................ 32 
11.2.4 Compliance with Trial Registration and Results Posting Requirements .................. 32 
11.2.5 Record Retention ................................................................................................. 32 
12.1 Sample Size and Analysis Plan ..................................................................................... 33 
12.2 Sample Size/Accrual Rate ........................................................................................... 34 
12.3 Stratification Factors .................................................................................................. 34 
12.4 Analysis of Endpoints .................................................................................................. 34 
12.4.1 
Analysis of Primary Endpoints ........................................................................ 34 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
vi 
 
12.4.2 
Analysis of Secondary Endpoints .................................................................... 34 
12.4.3 
Analysis of Exploratory Endpoints .................................................................. 34 
12.5 Interim Analysis .......................................................................................................... 35 
12.6 Reporting and Exclusions ............................................................................................ 35 
12.6.1 
Evaluation of Toxicity ..................................................................................... 35 
12.6.2 
Evaluation of Response .................................................................................. 35 
13. ADVERSE EVENT REPORTING REQUIREMENTS ................................................................ 35 
13.1 Adverse Event Definition ............................................................................................ 35 
13.1.1 
Investigational Drug, FMP250, Risks (Potential Adverse Events) ...................... 36 
13.1.2 
FMT Procedural Risks (Potential Adverse Events)............................................ 38 
13.1.3 
Risk from colonoscopy and sigmoidoscopy (Potential Adverse Events) ............ 38 
13.1.4 
Risk from Medical Record Review (Potential Adverse Events) ......................... 38 
13.1.5 
Risk from Blood Draws (Potential Adverse Events).......................................... 38 
13.1.6 
Risk from Placebo (Potential Adverse Events) ................................................. 39 
13.1.7 
Risk from Psyllium Husk (Potential Adverse Events) ........................................ 39 
13.1.8 
Risk from Anti-Diarrheal Agents (Potential Adverse Events) ............................ 39 
13.1.9 
Risk for Women of Child-Bearing Potential ..................................................... 39 
13.1.10 
Likelihood of Any Adverse Event .................................................................... 40 
13.1.11 
Adverse Event Characteristics and Related Attributions .................................. 40 
13.1.12 
Recording of Adverse Events .......................................................................... 41 
13.1.13 
Reporting of AE to WCM IRB .......................................................................... 41 
13.1.14 Reporting of AE to FDA ....................................................................................... 41 
13.1.15 
Reporting Events to Participants .................................................................... 41 
13.1.16 
Reporting of Pregnancy .................................................................................. 41 
13.2 Definition of SAE ........................................................................................................ 42 
13.2.1 
Reporting of SAE to IRB .................................................................................. 42 
13.2.2 
Reporting of SAE to FDA [For Protocols Where WCMC is the Sponsor-
Investigator] .................................................................................................................. 42 
13.2.3 
Reporting of SAE to OpenBiome ..................................................................... 43 
13.3 AE/SAE Follow Up ....................................................................................................... 43 
13.4 Time Period and Frequency for Event Assessment ....................................................... 43 
13.4.1. AE/SAE Monitoring ............................................................................................. 43 
13.4.2. AE/SAE Assessment ............................................................................................ 46 
13.4.2.1 Assessment of Severity...................................................................................... 46 
13.4.2.2 Assessment of Causality .................................................................................... 46 
14. UNANTICIPATED PROBLEMS INVOLVING RISKS TO SUBJECTS OR OTHERS........................ 47 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSO) 47 
14.1.2 
Unanticipated Problem Reporting .................................................................. 48 
15. DATA AND SAFETY MONITORING PLAN (DSMP) .............................................................. 48 
15.1. Plan for informed consent compliance ....................................................................... 49 
15.2. Plan for HIPAA compliance ........................................................................................ 49 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
vii 
 
15.3. Annual Reporting ...................................................................................................... 49 
15.4. Halting Rules ............................................................................................................. 50 
References ......................................................................................................................... 51 
 
 
 
 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
viii 
 
Statement of Compliance 
 
The trial will be conducted in accordance with International Conference on Harmonization Good Clinical 
Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and the Weill Cornell 
Medical College Terms and Conditions of Award. The Principal Investigator will assure that no deviation 
from, or changes to the protocol will take place without prior agreement from the Investigational New Drug 
(IND) or Investigational Device Exemption (IDE) sponsor, funding agency and documented approval from 
the Institutional Review Board (IRB), except where necessary to eliminate an immediate hazard(s) to the 
trial participants. All personnel involved in the conduct of this study have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval.  Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study.  All changes to the consent form will 
be IRB approved; a determination will be made regarding whether a new consent needs to be obtained 
from participants who provided consent, using a previously approved consent form. 
 
 
Confidentiality Statement 
 
This document is confidential and is to be distributed for review only to investigators, potential 
investigators, consultants, study staff, and applicable independent ethics committees or institutional review 
boards. The contents of this document shall not be disclosed to others without written authorization from 
WCM. 
 
 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
ix 
 
List of Abbreviations 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CTSC 
Clinical Translational Science Center  
DSMB 
Data Safety Monitoring Board 
DSMP 
Data Safety Monitoring Plan 
FDA 
Food and Drug Administration 
FMT 
GCP 
Fecal Microbiota Transplantation 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HRBFA 
Human Research Billing Analysis Form 
HUD 
IB 
Humanitarian Use Device  
Investigator Brochure 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption  
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
PHI 
Protected Health Information 
PI 
Principal Investigator 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SUSAR 
Suspected Unexpected Serious Adverse Reaction  
UC 
UIRTSO 
Ulcerative Colitis 
Unanticipated Problem Involving Risks to Subjects or Others 
WCM 
Weill Cornell Medicine 


IRB Protocol #: 19-04020045 
Version Date: 02/23/2024 
  
1 
1. Protocol Summary 
 
Full Title: 
 
 
 
 
A randomized, placebo-controlled clinical trial examining the efficacy of 
Fecal Microbiota Transplantation (FMT) and subsequent dietary fiber in 
patients with moderate ulcerative Colitis 
Short Title:  
 
 
 
MINDFUL  
Clinical Phase:  
 
 
II  
Principal Investigator:  
 
Randy Longman, MD PhD 
Study Description:  
 
A double-blind, randomized, placebo-controlled clinical trial examining 
the efficacy and safety of Fecal Microbiota Transplantation (FMT) and 
high fiber supplementation in patients with active mild to moderate 
Ulcerative Colitis (UC). All enrolled subjects will provide serological, stool 
and mucosal specimen at each clinic visit to help further define the 
alterations in microbial profiles and immune cell function in response to 
psyllium fiber after FMT treatment.  
Sample Size: 
 
N=135, 45 subjects per study arm  
Enrollment: 
 
This study will enroll 135 subjects and screen up to 150 subjects.   
Study Population: 
 
All male and female participants at least 18 years of age with prior history 
of mild to moderate Ulcerative Colitis and willing to undergo standard of 
care colonoscopy to assess active disease for study eligibility.  
Enrollment Period: 
 
2019-2023  
Study Design: 
 
This is a randomized, double-blind, placebo-controlled clinical trial with 
the following treatment assignments: 
1. Investigational FMP250 (one-time) at week 0 
a. Subjects in this group will also blindly receive 
placebo 
FMP250 
at 
week 
8 
by 
flexible 
sigmoidoscopy. 
2. Investigational FMP250 (one-time) at week 0 + Psyllium fiber 
(2x/day for 8 weeks) 
a. Subjects in this group will also blindly receive 
placebo 
FMP250 
at 
week 
8 
by 
flexible 
sigmoidoscopy. 
3. Placebo FMP250 (one-time) at week 0 with or without 
Psyllium fiber (2x/day for 8 weeks)  
a. Subjects in this group will also blindly receive 
investigational FMP250 at week 8 by flexible 
sigmoidoscopy. 
Subjects will blindly receive the investigational or placebo FMP250 
treatment only if they meet all inclusion and exclusion criteria during the 
day 0 screening colonoscopy. Subjects will receive a follow-up phone call 
or return for a clinic visit every 2 weeks post-FMT until week 12. At week 
8 post-FMT, all subjects will be evaluated by flexible sigmoidoscopy in the 
clinic.  Stool and blood samples will be collected for research from 
subjects at day 0 prior to FMT, week 4 post-FMT, week 8 post-FMT, and 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
2 
 
week 12 post-FMT. Mucosal biopsies will also be taken during the initial 
colonoscopy at day 0 and during the follow-up flexible sigmoidoscopy at 
week 8. Subjects randomized into the placebo cohort will receive 
investigational FMP250 and subjects randomized into the investigational 
cohort will receive placebo FMP250 by flexible sigmoidoscopy at the 
week 8 clinic visit (after week 8 endpoint data are collected). All subjects 
will return 4 weeks later at week 12 for a clinic visit. All subjects will be 
contacted for follow-up phone calls every subsequent 6 months for the 
next year. 
Description of Site(s) Enrolling 
Participants: 
              The Jill Roberts Center for Inflammatory Bowel Disease 
Gastroenterology and Hepatology at David H. Koch Center 
Weill Cornell Medicine/ New York Presbyterian Hospital 
1283 York Avenue, 9th Floor 
New York, NY 10065 
Study Duration: 
 
2019-2023 
Participant Duration: 
 
12 weeks + 1 year follow up 
Study Drug Name:  
 
FMT Lower Delivery Microbiota Preparation (FMP250) 
Intervention Description: 
Subjects will receive up to 250cc of blinded investigational or placebo 
FMP250 delivered by colonoscopy once at day 0. Placebo treatment 
group will receive investigational FMP250 while the investigational 
treatment groups will receive placebo FMP250 by flexible sigmoidoscopy 
at week 8. 
 
 
 
 
 
 
 
 
 
 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
3 
 
1.1 Study Schematic 
  
  
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
4 
 
 
 
1.2 Study Objectives 
 
1.2.1  Primary Objective  
 
To assess if a dietary prebiotic supplementation (psyllium husk powder) in addition to FMT is 
superior to FMT or prebiotics alone to achieve clinical response in patients with mild to 
moderate Ulcerative Colitis compared to FMT or prebiotic alone. 
 
1.2.2  Secondary Objective(s)  
 
To assess if a dietary prebiotic supplementation in addition to FMT compared to either alone 
is superior in achieving clinical remission, endoscopic response or endoscopic remission, 
histologic response or remission rates. 
 
To assess clinical response / remission and endoscopic response and remission of Fecal 
Microbiota Transplantation (FMT) for the management of active mild to moderate Ulcerative 
Colitis compared to placebo. 
 
1.2.3  Exploratory Objective(s) 
 
 
 
To define the microbial determinants of successful microbial manipulation therapy from 
mucosal, blood and stool samples collected at day 0 prior to FMT and week 8 post-FMT. 
 
To define the impact of diet on the clinical and microbiome outcomes of Fecal Microbiota 
Transplantation (FMT) for the management of active mild to moderate Ulcerative Colitis 
compared to FMT or prebiotic alone. 
 
2. Background 
 
2.1 Ulcerative Colitis  
 
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) characterized by recurring 
episodes of inflammation limited to the mucosal layer of the colon. This chronic disease may even 
extend to all divisions of the large intestine and in 95% of its cases it involves the rectum1. The highest 
prevalence of UC is reported in Europe (505 cases per 10,000 in Norway) and North America (286 per 
100,000 in USA)2 with approximately 38,000 new cases each year3. The severity of this illness ranges 
from mild well-controlled symptoms to severe uncontrolled manifestations which require 
hospitalizations, blood transfusions, surgical interventions, and may even cause death.  
Current treatment for UC relies heavily on drug therapies to target host factors and immune 
suppression for the management of symptoms, prevention of relapses, and induction of remission. 
Aminosalicylates are the first line therapy for newly diagnosed mild to moderate UC. Although safe 
and effective in mild to moderate UC, few alternatives exist, and non-compliance is commonplace. 
Patients who relapse often require escalation to immunomodulators or steroid therapy, which 
similarly have limited safety profiles. Steroids are efficient for induction therapy; however, they are 
known to have significant side effects and do not provide benefit for maintenance therapy. 
Immunomodulators, such as azathioprine and 6-mercaptopurine, similarly have a significant side 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
5 
 
effect profile and limited efficacy in inducing remission. They increase the risk of lymphoma and other 
malignancies, and may result in bone marrow toxicity and hepatotoxicity4,5. Mainstay of treatment 
for patients with UC who fail 5-ASA therapy are anti-tumor necrosis factor drugs (anti-TNFs), anti-
integrin therapy (vedolizumab) and the janus kinase inhibitor tofacitinib, which are often efficacious 
with a clinical response rate reported to be as high as 70%6. Aside from vedolizumab, these therapies 
carry serious potential adverse effect profiles7-9. Furthermore, all have significant cost.  Although there 
are numerous medications available for the management of UC, patients commonly become steroid-
dependent and/or refractory to medical management and eventually require surgery10. Patients with 
poorly controlled UC are often desperate for a different method to control their symptoms due to the 
tremendous pain and suffering, loss of productivity, and disease-associated financial burdens.  
Patients with IBD, including UC, harbor various genetic variants in genes regulating immune system 
function11. These variants can increase susceptibility to abnormal immune responses to 
microorganisms within the gut resulting in persistent inflammation and the debilitating inflammation 
of UC. Although the etiology of UC is not well understood, the presence of certain beneficial bacteria 
can prevent disease in experimental animal models of colitis while the loss of these bacteria or 
overgrowth of other types can trigger induction of inflammatory responses and debilitating symptoms 
of IBD12. The vast majority of treatment modalities for UC target host factors of inflammation. Despite 
substantial research efforts to understand the role of commensal bacteria in disease and 
pathogenesis, the therapeutic role for microbial manipulation in active UC is less well defined. 
Although antibiotics are used in the treatment of infectious complications of UC, their role for 
induction or maintenance therapy is unsupported by several different clinical studies. Therapeutic 
manipulation of intestinal microbiota can be achieved by other methods than antibiotics. 
 
2.2 Fecal Microbiota Transplant (FMT) 
 
FMT is an emerging therapy that transfers healthy donor fecal bacteria to patients suffering from GI 
illnesses with the goal of re-establishing a healthy intestinal bacterial community in those patients13. 
FMT has shown to be effective in the management of various diseases, most notably Clostridium 
difficile infections (CDI). A randomized control trial from 2013 in the New England Journal of Medicine 
evaluated the use of FMT in the management of CDI. The results were promising: an overall cure of 
15 out of 16 patients (94%)14.  
There are 3 major clinical trials that have looked at the safety and efficacy of FMT for the management 
of UC. In the first randomized, placebo controlled clinical trial by Rossen et. al, 50 patients with active 
UC (23/25) received FMT (donor stool) or placebo (autologous stool) via nasoduodenal delivery twice 
during the 12 weeks study period15. Analysis showed 41% vs 25% efficacy with no statistical 
differences between the groups15. Moayyedi et al. enrolled 75 study participants who received donor 
FMT or placebo (water) weekly enemas for 6 weeks16. 24% of patients who received FMT showed 
clinical response compared with 5% in placebo group and the difference between the groups was 
significant16. Paramsothy et al.’s study delivered donor FMT or placebo in 85 (42/43) patients via 
colonoscopy followed by 5 times per week enema for 8 weeks17. Primary outcome was reached by 
27% of patients from FMT group compared with 8% in placebo group with significant differences 
between the groups17. These clinical findings indicate that despite the variation of delivery and 
dosage, FMT appears to be safe and effective for induction and remission of UC and can be included 
as an adjunctive therapeutic modality for management of the disease. 
Our collaborative team recently completed a pilot study at Weill Cornell Medicine aimed at assessing 
the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active 
UC18. We performed a single-center, prospective, open-label pilot study to evaluate the safety and 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
6 
 
efficacy of two-donor fecal microbiota preparation (FMP) delivery by colonoscopy. The primary 
outcome was clinical response at week 4 with secondary endpoints including clinical remission, 
mucosal healing at week 4 and safety profile. Overall, 34 patients were screened, and 20 patients 
were enrolled. Seven patients (35%) achieved a clinical response (Mayo score ≥ 3 and a bleeding 
subscore ≤1) by week 4. Three patients (15%) were in clinical remission at week 4 (Mayo score ≤2 and 
no subscore >1), and two of these patients (10%) achieved mucosal healing (endoscopy subscore of 
0). Paired analysis showed a significant improvement in Mayo score (Median decrease of 1.5, p = 0.03) 
and endoscopic subscore (Median decrease of 0.5, p = 0.002). 
 
Further microbiome analysis revealed that signatures of donor-derived microbiota correlate with 
clinical response18. Taxonomic analysis revealed enrichment of Ruminococcus, Odoribacter, and 
Christensenellaceae in healthy donors and responders, but absent in patients with active disease. In 
contrast, patients who did not respond to treatment had failed to eradicate Fusobacteria, Finegoldia 
and Collinsella. To determine the fecal microbial composition and function at species/strain level, we 
performed metagenomic sequencing of a complete set of three samples (donor, recipient pre, 
recipient post) from three responder patients, who had met the primary endpoint of our pilot FMT 
trial. Relative abundances of microbial species were determined by Metaphlan2 and protein encoding 
genes profiling were determined by HUMAnN2 pipeline. Analysis of the previously identified 
transferrable genus of Ruminococcus revealed, that of the several species and strains present in the 
patient samples, abundance of only Ruminococcus torques was significantly enriched in responders. 
Collectively, this data revealed that response to single colonoscopic delivery correlated with 
engraftment of key species of transferrable bacteria in the responder patients. Further studies are 
required to determine factors that enhance the engraftment of these bacteria and increase the 
efficacy of this therapy. 
 
2.3 Dietary Fiber Supplementation 
Dietary supplements are important factor that may regulate engraftment of beneficial donor bacteria.  
Short-chain fatty acids, such as butyrate, are important colonic metabolites provided by diet-based 
carbohydrates fermented by commensal bacteria in the gut microbiota19-21. Butyrate has been well 
characterized by in vitro studies to protect the epithelium against pathogens by upregulating mucins, 
the antimicrobial peptides responsible for the mucosal layer, and by increasing the expression of tight 
junction proteins to reduce intestinal permeability19. Butyrate is an inhibitor of nuclear factor NF-κB, 
a transcription factor necessary for the expression of pro-inflammatory proteins20, and an 
immunomodulator of macrophages, dendritic cells (DC), and T cells19. Studies in animal models 
demonstrate that supplemental butyrate upregulates regulatory T cells and ameliorates intestinal 
inflammation22,23. Recent studies evaluated the use of various fiber-based diets in animal models of 
IBD with indigestible fibers having strongest effect on mucosal inflammation23-25. These curative 
properties substantiate the potential role of a post-transplant fiber therapy as necessary to prolong 
remission and de-escalate immunosuppressive treatments by promoting microbial engraftment and 
mucosal healing.  
Efficacy of dietary fiber for management of IBD has been long investigated using fiber rich diet or fiber 
supplements, largely with variable effects. Several clinical trials have demonstrated the therapeutic 
benefit in UC patients with psyllium having significant effect for maintenance of remission and 
germinated barley for active UC20. Importantly, none of the studies reported disease exacerbation or 
early relapse in patients with IBD. Therefore, controlled data demonstrating the effect of fiber as a 
prebiotic regulator of engraftment and FMT outcome in UC has yet to be explored. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
7 
 
 
2.4 Rationale  
 
The current standard of care for ulcerative colitis relies heavily on medications targeting host factors 
for the management of symptoms, prevention of relapses, and induction of remission. Although there 
are numerous medications available for the management of UC, patients commonly become steroid-
dependent and/or refractory to medical management.  FMT is an emerging treatment modality for 
UC.  Although the clinical efficacy of FMT for UC is variable, our preliminary results suggest that 
response may correlate with the engraftment of key beneficial microbiota18. Therefore, our study is 
aimed at determining the role of supplemental fiber as a mechanism to enhance the efficacy of FMT.  
Results from this study have the potential to offer pioneering data on the ability of prebiotics to shape 
microbial engraftment. This intervention has the potential to impact FMT in UC and microbial 
manipulation therapy more broadly. 
 
Thus, the overall goal of this study is to test the role of supplemental psyllium in the clinical outcome 
and microbial engraftment of FMT for ulcerative colitis. 
 
2.4.1 
FMP Lower Delivery Microbiota Transplant (FMP250)  
In our previous single-center, prospective, open-label pilot study, we sourced our two-
donor fecal microbiota preparation (FMP) from OpenBiome and found that FMP delivery 
by colonoscopy not only was safe but also efficacious in improving clinical response as a 
therapeutic alternative for UC patients. Therefore, we propose to source OpenBiome’s 
FMT Lower Delivery Microbiota Preparation (FMP250) as the investigational drug in this 
clinical trial.  
2.4.2 
Psyllium Husk Powder 
 
Highly viscose, gel-forming soluble fibers have been found to lower elevated serum 
cholesterol concentrations, improve glycemic control, and have stool regularity 
benefits28. We are interested in utilizing a fiber that can provide regularity benefits to aid 
in stool passage. Regularity benefits are attainable by soluble gel-forming fibers if they 
are able to resist fermentation and have a high-water retention capacity. We have chosen 
psyllium as our dietary supplement to pair with FMP250 because it is a non-fermented, 
natural fiber that is viscose, gel-forming, and soluble and is an FDA-approved over the 
counter product. Psyllium is composed of stackable polymer chains, which contribute to 
its viscosity, that crosslink to form a gel to promote water retention in the colon, which 
causes a softer stool by protecting it against dehydration. The fiber will help the stool 
remain whole and bulky throughout its passage in the large intestine. We chose psyllium 
over a very similar fiber called b-glucan because various RCTs demonstrated that 
fermentable fibers in the colon caused no effect on stool composition. Interestingly, 
psyllium has the capacity to provide regularity benefits by two mechanisms. It can either 
soften stool or increase bowel movements for constipation but more importantly for this 
study, it is able to harden stool and decreased bowel movements for diarrhea.  
 
Psyllium husk powder will be purchased commercially by WCM investigators and 
provided to subjects in the fiber treatment assignment if they meet all inclusion criteria 
during their screening visit, excluding the endoscopic criteria.  


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
8 
 
 
2.5  Risk/Benefit Assessment  
 
 
2.5.1 
Known Potential Risks  
 
2.5.1.1.  FMT-related: (adapted from OpenBiome FMP250 Investigator Brochure V4.0): 
 
The following adverse reactions have been reported in scientific literature to be 
commonly caused by FMT material within 24 hours post-procedure: 
• 
Transient diarrhea, abdominal cramps/discomfort, and nausea 
• 
Fever, bloating, belching, vomiting, borborygmi 
• 
Constipation and flatulence  
• 
Flares in IBD patients 
These symptoms are usually self-limiting and of short duration. They may also 
be attributable to the delivery modality (e.g. colonoscopy or upper 
endoscopy) or underlying disease. 
  
According to Openbiome and/or peer-reviewed literature, the following serious 
adverse events are potential risks that have been observed by FMT-based 
products (not specifically Openbiome) or included based on biological plausibility: 
1. Infection  
a. Bacterial infections from multi-drug resistant organisms (MDROs) 
(i.e. 
extended 
spectrum 
beta-lactamase 
(ESBL)-producing 
Enterobacteriaceae, 
vancomycin-resistant 
enterococci 
(VRE), 
carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-
resistant Staphylococcus aureus (MRSA)) 
b. Shiga Toxin-Producing E. Coli (STEC) Infections 
c.  Enteropathogenic E. Coli (EPEC) Infections 
d. SARS-CoV-2 Infection  
e. Diverticulitis, bacteremia, cytomegalovirus colitis, fever, diarrhea 
encephalophagy and pancytopenia, Influenza B and diarrhea, 
norovirus gastroenteritis 
f. Monkeypox Infection 
2. Aspiration from upper GI delivery of FMT 
3. GI complications (i.e. diarrhea, abdominal pain, appendicitis, peritonitis, IBD 
flare, and diverticulitis) 
4. Allergy/Anaphylaxis 
5. Autoimmune disorders 
a. Exacerbation of pre-existing autoimmune conditions 
b. Development of Rheumatoid arthritis, Sjogren’s disease, peripheral 
neuropathy, idiopathic thrombocytopenic purpura 
6. Non-infectious disease transmission (i.e. obesity, metabolic syndrome, 
cardiovascular disease, neurologic disorders, psychiatric conditions and 
malignancy) 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
9 
 
 
2.5.1.2.  Psyllium-related  
 
The FDA {CFR - Code of Federal Regulations Title 21} recommends sufficient liquid 
consumption when taking dried psyllium husk to avoid any potential risk for 
choking. In geriatric patients, some rare side effects may include abdominal 
discomfort, nausea, mild abdominal cramps, griping, and faintness34. 
Additionally, our investigators hypothesize that bloating could occur as a side 
effect. 
 
2.5.2 
Known Potential Benefits  
 
2.5.2.1.  FMT-related  
Our previous pilot study found 35% of subjects clinically responded and 15% went 
into clinical remission when evaluated at the 4 weeks post-FMT18. Similar clinical 
trials found improvement in clinical response in subjects treated with FMT when 
compared to the placebo groups15-17. However, we cannot and do not guarantee 
that subjects will receive any benefits from this study. We hope the information 
learned from this study will benefit other patients with ulcerative colitis in the 
future. 
 
2.5.2.2.  Psyllium-related  
 
Various dietary fiber interventions report that it may be beneficial for IBD 
patients, however, their results do not consistently demonstrate alleviation of 
disease activity and/or inducement of clinical remission31. Therefore, we cannot 
and do not guarantee that subjects will receive any benefits from psyllium in 
combination with FMP250. We hope the information learned from this study will 
benefit other patients with ulcerative colitis in the future. 
 
2.5.3 
Assessment of Potential Risks and Benefits 
 
Ulcerative colitis remains a major medical problem.  Steroids, immunosuppressants, and biologic 
therapies are the mainstay of therapy for active disease.  These medications are all associated 
with a range of side effects.  Recent studies have demonstrated the potential efficacy of FMT for 
the treatment of mild to moderate UC.  Although some risks exist including procedural risk 
associated with colonoscopic delivery, this emerging therapeutic strategy appears to be more 
effective than placebo in inducing clinical remission.  This study will additionally assess the use of 
psyllium husk as a prebiotic supplement to enhance the efficacy of FMT.  We do not anticipate 
additional risk associated with psyllium. 
 
A FMT placebo arm with psyllium supplement is required to assess the potential clinical efficacy 
of psyllium alone and to serve as a placebo control for FMT.  The placebo arm is required in order 
to determine the efficacy of FMT + psyllium over psyllium alone.  However, at the end of the study, 
investigational FMT will be provided for patients in the psyllium + placebo arm.  
 
Importantly, no SAEs have been found in any previous FMT intervention, including our pilot study, 
to be definitely attributed to the investigational drug. Therefore, we believe the potential benefit 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
10 
 
of clinical and endoscopic response or remission from FMT concurrently with psyllium 
supplementation outweighs the risks. 
 
2.6 Correlative Studies Background 
 
Our collaborative team recently completed a pilot study at Weill Cornell Medicine aimed at assessing 
the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active 
UC18. We performed a single-center, prospective, open-label pilot study to evaluate the safety and 
efficacy of two-donor fecal microbiota preparation (FMP) delivery by colonoscopy. The primary 
outcome was clinical response at week 4 with secondary endpoints including clinical remission, 
mucosal healing at week 4 and safety profile. Overall, 34 patients were screened, and 20 patients 
were enrolled. Seven patients (35%) achieved a clinical response (Mayo score ≥ 3 and a bleeding 
subscore ≤1) by week 4. Three patients (15%) were in clinical remission at week 4 (Mayo score ≤2 and 
no subscore >1), and two of these patients (10%) achieved mucosal healing (endoscopy subscore of 
0). Paired analysis showed a significant improvement in Mayo score (Median decrease of 1.5, p = 0.03) 
and endoscopic subscore (Median decrease of 0.5, p = 0.002).  The present will test the hypothesis 
that prebiotic supplementation with psyllium will increase that clinical response rate over FMT alone.  
Furthermore, the current study will assess additional impact on clinical and endoscopic remission 
rates as well as placebo FMT. 
 
Further microbiome analysis revealed that signatures of donor-derived microbiota correlate with 
clinical response18. Taxonomic analysis revealed enrichment of Ruminococcus, Odoribacter, and 
Christensenellaceae in healthy donors and responders, but absent in patients with active disease. In 
contrast, patients who did not respond to treatment had failed to eradicate Fusobacteria, Finegoldia 
and Collinsella. To determine the fecal microbial composition and function at species/strain level, we 
performed metagenomic sequencing of a complete set of three samples (donor, recipient pre, 
recipient post) from three responder patients, who had met the primary endpoint of our pilot FMT 
trial.  Relative abundances of microbial species were determined by Metaphlan2 and protein encoding 
genes profiling were determined by HUMAnN2 pipeline. Analysis of the previously identified 
transferrable genus of Ruminococcus revealed, that of the several species and strains present in the 
patient samples, abundance of only Ruminococcus torques was significantly enriched in responders. 
Collectively, this data revealed that response to single colonoscopic delivery correlated with 
engraftment of key species of transferrable bacteria in the responder patients. This study will 
therefore evaluate the hypothesis that psyllium prebiotic supplementation will change the species 
engraftment. 
 
3. Study Design 
 
3.1 Overall Design 
 
Hypothesis: A high fiber diet will promote the engraftment of healthy donor microbiota and increase 
the efficacy of FMT in UC patients. If successful, this proposal will help us to define the role for dietary 
fiber supplementation in promoting microbial determinants of successful FMT and enhance the 
clinical efficacy of FMT for UC. 
Study Phase: II 
Study Design: Double-blinded, randomized, placebo-controlled clinical trial 
Study Drug: FMT Lower Delivery Microbiota Preparation (FMP250)  
Study Arms: 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
11 
 
Group 1: Investigational FMT  
o Subject will receive investigational FMT once at day 0 colonoscopy  
o Subject will receive placebo FMT once at week 8 flexible sigmoidoscopy 
o Observed for 12 weeks  
 
Group 2: Investigational FMT + psyllium fiber  
o Subject will receive investigational FMT once at day 0 colonoscopy  
o Fiber supplementation of 1 teaspoon 2x/day for 8 weeks 
o Subject will receive placebo FMT once at week 8 flexible sigmoidoscopy 
o Observed for 12 weeks  
 
Group 3: Placebo FMT with or without psyllium fiber  
o Subject will receive placebo FMT once at day 0 colonoscopy  
o Half of subjects will be randomized to receive fiber supplementation of 1 teaspoon 
2x/day for 8 weeks  
o Subject will receive investigational FMT once at week 8 flexible sigmoidoscopy  
o Observed for 12 weeks  
Site:  
Weill Cornell Medical Center / New York Presbyterian Hospital (Clinical Facility) 
• 
The Jill Roberts Inflammatory Bowel Disease Center at David H. Koch Center 
Weill Cornell Medicine Belfer Research Building (Research Laboratory Facility)  
• 
The Jill Roberts Institute for Research in Inflammatory Bowel Disease 
 
Methods to Minimize Bias: 
1. Randomization Bias 
a. A series of randomized blocks of fixed size will be generated with a 1:1:1 allocation 
ratio. This will provide assurance that after a given block has completed subject 
enrollment, there will the same number of subjects assigned to each of the three 
study arms. Additionally, the specific number of subjects within any randomization 
block (i.e., block size) will be blinded to all investigators to avoid any risk for 
unblinding treatment arms prior to the primary endpoint evaluation. 
2. Unblinding Bias 
a. Clinicians are blinded throughout the study so they will assess the clinical response at 
week 8 and will be unblinded only once this independent scoring is completed for all 
135 enrolled subjects. This will reduce the risk of potential bias by the clinician as all 
treatment groups will receive treatment (blinded investigational or placebo FMP250) 
at week 8 by flexible sigmoidoscopy. 
 
3.2 Scientific Rationale for Study Design 
The ability to manipulate the human gut microbiome and alter mucosal and systemic immunity 
remains a central question in the study of IBD. We have previously completed a pilot study for FMT 
at Weill Cornell and have the clinical research infrastructure and clinical expertise to recruit patients, 
characterize their response, and complete the data analysis. Work from our lab and others has defined 
the role for specific bacteria in inducing immune responses in mouse models. We also have defined 
diagnostic signatures of microbial profiles associated with inflammatory disease phenotype in humans 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
12 
 
including rheumatoid arthritis and IBD. Emerging clinical data provides evidence for the clinical 
efficacy of FMT in patients with ulcerative colitis (UC). Preliminary data from our own research 
suggests that engraftment and/or particular microbial species correlate with clinical outcome, 
however the factors that determine microbial engraftment are not well defined. Therefore, we 
designed a randomized, double-blind, placebo-controlled study to examine the possibility of 
improving the clinical outcome and microbial engraftment of FMP250 by using prebiotic fiber 
supplementation in active UC patients. Study subjects will be randomized into three groups: (1) 
FMP250+Fiber, (2) FMP250-Fiber, and (3) PlaceboFMP250 with or without Fiber. Given that fiber alone 
has not shown significant benefits previously in many UC studies27, we hypothesize that subjects given 
PlaceboFMP250+Fiber will allow us to assess the placebo rate for FMT (FMP250only vs. 
PlaceboFMP250+Fiber). Also, considering that we will utilize single donor FMP250 samples, 
comparing subjects given FMP250only and FMP250+Fiber will allow us to scientifically assess primary 
endpoints of the impact of prebiotic supplement on engraftment and efficacy. PlaceboFMP250-Fiber 
will remove any risk of unblinding and will maintain the integrity of our double blinded study. 
Additionally, previous reports have suggested that dietary effects of fiber can have critical effects on 
the microbiome28.  Moreover, these effects can, in part, be mediated by the impact on T cell repertoire 
and function29.  These pre-clinical data may have a critical impact on the efficacy of FMT in UC, but 
human data are limited. To address this limitation, we will perform metagenomic sequencing on 
donor and recipient samples from this trial to assess the potential impact on beneficial bacterial strain 
engraftment. Also, as we have previously done, immune cell characterization will be performed to 
assess the potential impact of fiber on T cell function.  
 
3.3 Justification for Dose  
 
FMP250 is 250cc of healthy fecal homogenates and a standard size offering for FMT prepared by 
OpenBiome. It is also the standard dosage used for FMT treatment of C. Difficile infection. Single dose 
delivery of FMP250 was chosen as per our previous pilot study and due to supply cost constraints.    
 
3.4 End of Study Definition 
 
A subject is considered to have completed the study if he or she has completed all phases of the study 
including the last visit, at week 12 depending on treatment assignment or the last scheduled 
procedure shown in the Schedule of Assessments (SoA), Section 6.1. The end of the study is defined 
as completion of the last visit or procedure shown in the SoA in the trial globally. 
 
4. Subject Selection 
 
4.1 Study Population 
 
Subjects with a diagnosis of ulcerative colitis who meet the inclusion and exclusion criteria and are 
willing to undergo a standard of care colonoscopy to confirm their eligibility to participate in this 
study.   
 
4.2 Inclusion Criteria 
1. Male or Female ≥ 18 years of age. 
2. Documentation of prior history of mild to moderate UC. 
3. Endoscopy confirmed active UC ≥ 15 centimeters at day 0 screening colonoscopy. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
13 
 
a. As defined by a total Mayo scoring of 4-10 with an endoscopic sub-score ≥ 1 and a 
stool frequency or rectal bleeding sub-score of ≥ 1. 
4. Patients must have a descending intact colon. 
5. Patients taking steroid or biologic therapy must be on a stable dose for 4 weeks prior to 
screening and maintained throughout the trial. 
6. Eligible patients willing to undergo serological and fecal screening testing prior to FMT to 
document baseline status:  
a. Urine Testing 
i. Pregnancy test (women with childbearing potential) 
b. Blood Testing 
i. B-HCG (research purposes) 
ii. CBC, ESR, CRP, and BMP (standard of care) 
iii. HIV, type I and II (standard of care) 
iv. Hepatitis A B C Profile (standard of care) 
v. RPR (treponema pallidum) (research purposes) 
vi. CMV IgM (standard of care) 
vii. Quantiferon-TB (standard of care) 
c. Stool Testing 
i. Calprotectin (standard of care) 
ii. Clostridium Difficile Toxin PCR (standard of care) 
iii. Ova & parasites (standard of care) 
iv. Gastrointestinal Pathogen PCR Panel (standard of care) 
1. Campbylobacter species 
2. Plesiomonas Shigelloides 
3. Salmonella Species 
4. Vibrio Species 
5. Vibrio cholerae 
6. Yersinia Enterocolitica 
7. Enteroaggregative E. coli (EAEC) 
8. Enterpathogenic E. coli (EPEC) 
9. Enterotoxigenic E. coli (LT/ST) 
10. Shigalike toxin producing E.coli I (STX/ST2) 
11. Cryptosporidium 
12. Cyclospora caretanensis 
13. Entamoeba Cayetanensis 
14. Giardia 
15. Adenovirus F 40/41 
16. Astrovirus 
17. Norovirus GI/GII 
18. Rotavirus A 
19. Sapovirus 
20. GID PCR INTERP 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
14 
 
7. Patients must discontinue anti-rCDI antibiotics (e.g. vancomycin, fidaxomicin) 48 hours prior 
to FMT delivery procedure.  
4.3 Exclusion Criteria  
 
1. Biopsy proven Crohn’s disease 
2. UC patients with severe disease (defined as a total mayo score >10)  
3. Clinical complications requiring emergent management (e.g. stricture, bowel obstruction, 
perforation and/or abscess) 
4. Concurrent C. difficile or other infections 
5. Primary sclerosing cholangitis 
6. Prior history of FMT 
7. Treatment for malignancy within past 5 years 
8. Active or latent tuberculosis 
9. Clinically meaningful laboratory abnormalities 
a. Hb: < 8 
b. ALT: greater than 3x the ULN (upper limit of normal) 
10. History of anaphylactic reactions to food allergens or allergy to psyllium husk  
11. Pregnancy or lactation 
12. Probiotic use in the 4 weeks prior to screening and for the duration of the trial 
13. Subject having any other condition that, in the opinion of the investigator, would jeopardize 
the safety or rights of the subject participating in the study, would make it unlikely for the 
subject to complete the study, or would confound the study. 
4.4 Lifestyle Considerations 
 
During this study, subjects will not be specifically instructed to restrict any lifestyle considerations. 
However, a 24—hour diet recall will be conducted during our screening clinic visit (day -28 to -3) with 
a clinical nutritionist/registered dietician or study physician at Jill Roberts IBD Center in efforts to 
accurately observe and record each subject’s daily eating patterns. See Section 6.1.1. for more details.  
 
4.5 Screen Failures  
 
Screen failures are defined as participants who consent to participate in the clinical trial and have 
potentially been randomized into a treatment assignment but do not meet all inclusion criteria, 
specifically the endoscopy scoring for active disease at the day 0 standard of care colonoscopy. A 
minimal set of screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, and any serious adverse event (SAE). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) at the day 0 
standard of care colonoscopy may be rescreened at a later time.  
 
4.6 Strategies for Recruitment and Retention 
 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
15 
 
This clinical trial will recruit potential participants from the Jill Roberts Center for Inflammatory Bowel 
Disease and related facilities of New York Presbyterian Hospital/Weill Cornell Medical Center where 
our investigators are members of the medical staff. The Jill Roberts Center for IBD is a high-volume 
practice, led by our investigator Dr. Ellen Scherl, with over 4,000 IBD patients and with a full-time 
clinical research team dedicated to investigator-initiated studies. Our clinical research personnel are 
responsible for the recruitment, screening, enrollment and allocation of participants in study groups. 
We anticipate to identify and screen approximately 150 potential study participants from within our 
practice but will subsequently enroll 135 subjects. We expect the accrual rate to be approximately 40 
to 50 subjects per year. 
 
Recruiting efforts for this study will not target potential participants based on their gender, race, or 
ethnicity. Recruitment strategies will include submitting a summary of the study to clinicaltrials.gov 
and to the Jill Roberts IBD Center Website: https://jillrobertsibdcenter.weillcornell.org/research-and-
clinical-trials/clinical-trials.  
 
Subjects will not be compensated with financial incentives at any point during the study. 
 
5. Registration Procedures 
 
5.1 Subject Registration (WCM only) 
 
Subjects will be registered within the WRG-CT as per the standard operating procedure for Subject 
Registration.  
 
 
 
5.2 Subject Registration (Sub-sites) 
 
 
 
Not Applicable.  
 
 
6. Study Procedures 
 
6.1 Schedule of Assessments 
 
Table 1. Schedule of trial events 
 
Day 
-28 to 
-3 
Day 
0 
Day 
1 
Wk 
2 
Wk 
4 
Wk 
 6 
Wk 
8 
Wk 
10 
Wk 
12 
Off 
Studyd 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Concurrent medication 
X --------------------------------------------------------------------- ----- X 
 
Treatment Randomization 
X 
 
 
 
 
 
 
 
 
 
Physical exam 
X 
 
 
 
X 
 
X 
 
X 
 
Vital signs + Height + Weight 
X 
 
 
 
X 
 
X 
 
X 
 
B-HCG (serum pregnancy test) 
(research purposes) 
X 
 
 
 
 
 
 
 
 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
16 
 
Urine Pregnancy Test (standard of 
care and research purposes) 
 
Xc 
 
 
 
 
X 
 
 
 
CRP: C-Reactive Protein (standard of 
care) 
X* 
 
 
 
 
 
X 
 
 
 
ESR: Erythrocyte Sedimentation 
Rate (standard of care) 
X* 
 
 
 
 
 
X 
 
 
 
CBCa (standard of care) 
X* 
 
 
 
 
 
X 
 
 
 
CMPb (standard of care) 
X* 
 
 
 
 
 
X 
 
 
 
Blood: HIV screen (standard of care) 
X* 
 
 
 
 
 
 
 
 
 
Blood: Hepatitis A B C Profile 
(standard of care) 
X* 
 
 
 
 
 
 
 
 
 
Blood: RPR (Treponema 
pallidum) (research purposes) 
X 
 
 
 
 
 
 
 
 
 
Blood: CMV IgM (standard of care) 
X* 
 
 
 
 
 
 
 
 
 
Blood: Quantiferon-TB (standard of 
care) 
X* 
 
 
 
 
 
 
 
 
 
Fecal Calprotectin (standard of care) 
X* 
 
 
 
 
 
X 
 
 
 
Stool: Ova &parasites (standard of 
care) 
X* 
 
 
 
 
 
 
 
 
 
Stool: Clostridium Difficile Toxin 
PCR (standard of care) 
X* 
 
 
 
 
 
 
 
 
 
Stool: Gastrointestinal Pathogen 
PCR Panele (standard of care) 
X* 
 
 
 
 
 
 
 
 
 
Screening Colonoscopy (standard of 
care) 
 
X 
 
 
 
 
 
 
 
 
Blinded (Investigational or 
Placebo) FMP250 Treatment 
 
X 
 
 
 
 
 
 
 
 
Follow-up Flex sigmoidoscopy 
(standard of care) 
 
 
 
 
 
 
X 
 
 
 
Blinded Investigational FMP250 
(research purposes) 
 
 
 
 
 
 
Placebo 
group 
only 
 
 
 
Blinded Placebo FMP250 (research 
purposes) 
 
 
 
 
 
 
Investiga
tional 
group 
only 
 
 
 
Mucosal Biopsy Collection (research 
purposes) 
 
X 
 
 
 
 
X 
 
 
 
Blood and Stool Collection 
(research purposes) 
X---------X 
 
 
X 
 
X 
 
 X 
 
Follow-Up Phone calls (research 
purposes) 
 
 
X 
X 
 
X 
 
X 
 
X 
Diet Recall with Clinical 
Nutritionist or study MD (research 
purposes) 
X 
 
 
 
 
 
 
 
 
 
Psyllium Fiber Supplements 
(research purposes) 
X-------------------------------------------------------X 
Adverse event evaluation 
              X ----------------------------------------------------------------------------------X 
*:     These standard of care laboratory tests must be done during the screening period. However, if the subject 
consents on page 5 of the informed consent form, recent laboratory results may instead be used if the 
subject had them conducted within 2 weeks of signing consent. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
17 
 
a: Complete Blood Count (WBC count, RBC count, Hb, Hct, platelet count) 
b:    Comprehensive Metabolic Panel (glucose, calcium, sodium, potassium, CO2, chloride, BUN, Creatinine) 
c:  Urine pregnancy test (women of childbearing potential) as standard of care for colonoscopy 
d:    Off-study evaluation for the following year. 
e:  Gastrointestinal Pathogen GI Panel (Campbylobacter species, Plesiomonas Shigelloides, Salmonella 
Species, Vibrio Species, Vibrio cholerae, Yersinia Enterocolitica, Enteroaggregative E. coli (EAEC), 
Enterpathogenic E. coli (EPEC), Enterotoxigenic E. coli (LT/ST), Shigalike toxin producing E.coli I (STX/ST2), 
Cryptosporidium, Cyclospora caretanensis, Entamoeba Cayetanensis, Giardia, Adenovirus F 40/41, Astrovirus, 
Norovirus GI/GII, Rotavirus A, Sapovirus, GID PCR INTERP) 
 
 
6.1.1 
Screening Visit (Days -28 to -3) 
 
• 
Informed consent 
• 
Medical history 
• 
Medication history 
• 
Physical exam 
• 
Blood Testing 
1. B-HCG (research purposes)  
2. CBC, ESR, CRP, and CMP (standard of care) * 
3. HIV, type I and II (standard of care) * 
4. Hepatitis A B C Profile (standard of care) * 
5. RPR (treponema pallidum) (research purposes) 
6. CMV IgM (standard of care) * 
7. Quantiferon-TB Gold Plus, 1 Tube (standard of care) * 
• 
Stool Testing 
1. Calprotectin (standard of care) * 
2. Clostridium Difficile Toxin PCR (standard of care) * 
3. Ova & parasites (standard of care) * 
4. Gastrointestinal Pathogen PCR Panel (standard of care) * 
▪ 
Campbylobacter species 
▪ 
Plesiomonas Shigelloides 
▪ 
Salmonella Species 
▪ 
Vibrio Species 
▪ 
Vibrio cholerae 
▪ 
Yersinia Enterocolitica 
▪ 
Enteroaggregative E. coli (EAEC) 
▪ 
Enterpathogenic E. coli (EPEC) 
▪ 
Enterotoxigenic E. coli (LT/ST) 
▪ 
Shigalike toxin producing E.coli I (STX/ST2) 
▪ 
Cryptosporidium 
▪ 
Cyclospora caretanensis 
▪ 
Entamoeba Cayetanensis 
▪ 
Giardia 
▪ 
Adenovirus F 40/41 
▪ 
Astrovirus 
▪ 
Norovirus GI/GII 
▪ 
Rotavirus A 
▪ 
Sapovirus 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
18 
 
▪ 
GID PCR INTERP 
• 
Treatment Randomization (blinded to clinician and subject) 
1. Fiber treatment groups must receive psyllium dietary supplements (2 
teaspoons/day) to begin on day -3 
• 
Diet Recall with Clinical Nutritionist/Registered Dietician or study MD 
1. A subjective dietary record will be assessed anytime during the screening 
period (day -28 to -3), either by an clinic or phone call consult, in conjunction 
with the registered dietitian (RD). This meeting will aim to capture detailed 
information about food and beverages consumed over a certain (typical) 
period of time as an estimate of usual intake. The discussion may begin with 
the RD asking the subject “Could you please walk me through a typical day in 
terms of what you eat and drink from the time you wake up until you go to 
sleep?” The RD may then assess what the subject normally eats on a regular 
weekday, and give them the opportunity to tell them a few different options 
they might have for breakfast, lunch and dinner as well as snacks (if their days 
vary). They may also review what kinds of fruits and vegetables they consume 
most commonly, as well as get a sense of how much added sugar is likely in 
the subject’s diet. 
• 
Stool and blood samples taken for research purposes 
o This can be collected anytime during the screening period or on the day 
of the screening colonoscopy, prior to blinded FMT treatment, but if the 
subject is randomized to receive psyllium fiber, then this should be 
collected before day -3 when they begin the fiber supplementation.  
 
*:     These standard of care laboratory tests must be done during the screening period. 
However, if the subject consents on page 5 of the informed consent form then recent 
laboratory results may instead be used if the subject had them conducted as standard of 
care within 2 weeks of signing consent. 
 
6.1.2 
Treatment Phase 
 
 
 
 
 
Eligible subjects will be randomly assigned to one of the three (Placebo or Investigational 
FMP250 +/- Psyllium) treatment groups.  A series of randomized blocks of fixed size will 
be generated with a 1:1:1 allocation ratio. This will provide assurance that after a given 
block has completed subject enrollment, there will be the same number of subjects 
assigned to each of the three study arms. 
 
Treatment assignment will be done during the screening visit because participants 
randomized to receive fiber supplementation must be provided two psyllium bottles to 
begin consumption 3 days prior the colonoscopy.  
 
 
6.1.2.1 Screening Colonoscopy (Baseline, Week 0 Day 0) 
 
• 
Urine pregnancy test as standard of care 
• 
Standard of Care Colonoscopy for diagnostic purposes  
1. Mucosal biopsies taken for diagnostic and research purposes 
• 
FMT delivery by colonoscopy for research purposes  


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
19 
 
1. If active disease, study physician will blindly administer placebo or 
investigational FMP250 
• 
Stool and blood samples taken for research purposes, if not previously collected 
during screening period (days -28 to -3). 
 
 
 
6.1.2.2 Clinic Visit 3 (Week 8 ± 5 day(s)) 
 
• 
Medical history (AE evaluation) 
• 
Medication history 
• 
Physical exam 
• 
Urine pregnancy test for research purposes 
• 
Flexible Sigmoidoscopy for diagnostic purposes  
1. Mucosal biopsies taken for research purposes 
2. Subjects in placebo group blindly receive investigational FMP250 . 
3. Subjects in investigational groups blindly receive placebo FMP250 
• 
Stool and blood samples taken for research purposes  
• 
Standard of Care Testing 
1. Fecal Calprotectin 
2. Serological CBC, ESR, CRP, and CMP 
 
6.1.3 
Follow-up Phase 
 
6.1.3.1 Phone Consults (+/- 2 days) 
• 
Day 1  
• 
Week 2 
• 
Week 6 
• 
Week 10 
• 
Every subsequent 6 months for the next year 
6.1.3.2 Clinic Visits  
• 
Visit 2 (Week 4 ± 3 day(s)) 
 
o Medical history (AE evaluation) 
o Medication history 
o Physical exam 
o Stool and blood samples taken for research purposes  
 
• 
Visit 4 (Week 12 ± 5 day(s))  
 
o Medical history (AE evaluation) 
o Medication history 
o Physical exam 
o Stool and blood samples taken for research purposes  
6.1.4 
COVID-19 Study Modifications  
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
20 
 
If necessary, video visits will be recorded in the deviation log and will be submitted to the 
IRB at the continuing review. Additionally, sample collection for research purposes may 
also be obtained by having essential research personnel mail the subject a ‘Fedex clinical 
pak’ prepackaged for exempt human specimen and provided with mailing instructions via 
phone. All shipping associated costs will be paid for by the research study’s account and 
a Fedex pick up from the subject’s home will be arranged to support “social distancing” 
practices. As per Fedex recommendations, the subject will leave the package on their door 
step to minimize interaction with essential Fedex personnel.  
 
7. Study Intervention 
 
7.1 Study Intervention/Device Description   
 
7.1.1 
Investigational and Placebo FMP250  
The proposed intervention will deliver 250 milliliters of FMP250 by colonoscopy to the 
investigational FMP250 treatment groups at day 0. The placebo treatment group will instead 
receive the placebo FMP250 by colonoscopy at day 0 and then the investigational FMP250 by 
flexible sigmoidoscopy at week 8.  
 
Investigational FMP250 is biologically active human fecal material that is pre-screened, tested, 
quarantined, stored, packaged, and labeled by OpenBiome. Placebo FMP250 is a control unit 
made of glycerol, saline, and food dye that is stored, packaged, and labeled identically to the 
investigational FMP250, to ensure blinding during delivery. Weill Cornell Medicine has contracted 
OpenBiome to supply 135 investigational FMP250 and 135 Placebo FMP250 directly to the 
Longman laboratory at Weill Cornell Medicine over the course of the study.  
 
7.1.2 
Psyllium Husk Powder 
All subjects assigned to the fiber treatment arms will be required to take 1 teaspoon 
(approximately 5 grams) of psyllium husk powder twice a day (morning and night) for 8 weeks, 
beginning 3 days prior to Week 0 screening colonoscopy. To simplify, enrolled participants will 
consume approximately 10g of psyllium per day for 59 days.  
 
The FDA characterizes psyllium seed husk as the dried form of a psyllium seed coat33.  
 
7.2 Availability 
 
FMP250 is an investigational drug that will be purchased by WCM investigators from OpenBiome.  
 
Psyllium Husk Powder, Organic is an FDA approved prebiotic fiber product that will be commercially 
sourced from NOW® Foods by WCM investigators for the purpose of our study. Any of the following 
information provided about their prebiotic product is accessible on their website: 
https://www.nowfoods.com/supplements/psyllium-husk-powder-organic.  
 
7.3 Acquisition and Accountability  
 
 
 
Psyllium Ordering and Shipping – Investigator-appointed Weill Cornell research staff will order 
Psyllium Husk Powder, Organic 12 oz. bottles, Item# 5966, UPC# 733739059666. This unit size 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
21 
 
contains sufficient psyllium for the four-week psyllium regimen, therefore each subject will receive 
two bottles for the required 8 week supplementation. Details regarding the ordering and shipping 
process will depend on the company selected to commercially supply this product. Bulk shipments 
will be ordered preceding subject enrollment into the study. The quantity of units will be determined 
by the availability of the commercial provider. 
 
Psyllium Inventory Records – The research coordinator for this study will maintain a careful record of 
the inventory. This included product arrival dates, expiration dates, lot numbers, and each unit’s 
subject assignment on a Psyllium Tracking Log. This form is required by the FDA, must be kept in a 
safe place and filled out for all units in the possession of the investigator and/or appointed staff. An 
example of this form is shown below:  
 
 
 
FMP250 Ordering and Shipping – Investigator-appointed Weill Cornell research staff will order units 
of Investigational or Placebo FMT material by either (1) submitting orders via an OpenBiome 
specialized online order form, or (2) placing shipment orders directly via phone calls or emails with 
the OpenBiome Clinical Research Associate assigned to the trial.  
 
OpenBiome Clinical Research Associates:  
Jonathan Watson  
P. 617-575-2201 ext. 794 
E. jwatson@openbiome.org 
Sally Kim  
E. sally@openbiome.org 
 
The initial shipment will need approximately 4-6 weeks to fill due to the internal review process of the 
study protocol, IRB approval, IND approval, and fully-executed contract conducted at OpenBiome. 
Upon approval, all subsequent shipments of the study agent will be expected to arrive 5-7 days after 
the original order is placed. 
 
FMP250 Inventory Records – Investigator-appointed Weill Cornell research staff will maintain a 
careful record of the inventory and disposition of all agents received from OpenBiome with the 
Material Tracking Log, an example is pictured below, provided with each shipment by OpenBiome. 
This form should be kept in a safe space and must be filled out for all units. Once completed, it must 
be returned to OpenBiome prior to ordering the next shipment.  
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
21 
 
 
7.4 Formulation, Appearance, Packaging, and Labeling  
 
7.4.1 
Investigational FMP250 Formulation and Appearance 
Investigational FMP250 is 25 grams of pre-screened and tested human donor stool diluted and 
homogenized in 12.5% glycerol and normal saline buffer. The solution is then filtered to 330 
microns and aliquoted directly into sterile 250mL high-density polyethylene bottles.  
Potential OpenBiome donors are extensively screened for eligibility prior to stool collection by 
completing an informed consent, a Donor Health Questionnaire (DHQ), an in-person interview, 
and a clinical examination by one of their healthcare professionals. During this eligibility 
screening, OpenBiome evaluates the potential donor’s infectious risk factors, potential 
microbiome-mediated conditions, general health status, in addition to their breastfeeding status 
and risk for pregnancy. If patients have completed and satisfied the requirements, OpenBiome 
then requires serological, stool, and nasal swab testing to be conducted.  
There is an extensive standard operating procedure, which can be found in the OpenBiome IB, 
that is followed to ensure production and process controls. Therefore, once these have been 
fulfilled, the filtered stool is aliquoted, labelled, and frozen at -20 and then to -80 degrees Celsius. 
Donor stool is collected at the beginning of a 60-day window and is not shipped for clinical use 
until the donor undergoes the screening process again. This secondary screening process requires 
the donor to be cleared by two clinicians, and their stool to be evaluated by a quality assurance 
officer at the end of the collection window. Donors satisfying all secondary screening criteria will 
be cleared for stool shipment. 
 
7.4.2 
Placebo FMP250 Formulation and Appearance 
Placebo FMP250 is a placebo control unit made of a sterile-filtered solution with 12.5% glycerol 
and normal saline buffer in addition to added brown food dye. Once the placebo ingredients are 
homogenized, the solution is sterile filtered through a .02um inline filter and aliquoted directly 
into sterile 250mL high-density polyethylene bottles. Bottles are labelled with a unique identifier 
and stored at -80ºC storage until the placebo lot has passed bioburden testing at which point 
material is released for use in clinical research trials. Considering the placebo product is masked 
by food coloring, it should be indistinguishable from the investigational FMP250 by appearance.  
 
7.4.3 
Psyllium Husk Powder, Organic Formulation and Appearance 
This product is comprised of organic soluble fiber from powdered psyllium seed husks. This 
commercially available fiber supplement is also corn-free, dairy-free, egg-free, gluten-free, sugar-
free, soy-free, nut-free, non-GMO, kosher, low sodium, organic and vegan/vegetarian. Natural 
color variation (beige to light brown) may be different between different units.  
 
7.4.3 
Manufacturing Addresses 
OpenBiome  
 
 
 
 
 
NOW Foods 
2067 Massachusetts Avenue 
 
 
 
395 S. Glen Ellyn Rd 
Cambridge, MA 02140  
 
 
 
Bloomingdale, IL 60108 
E. info@openbiome.org  
 
 
 
P. (888-669-3663) 
P. (617) 575-2201  
 
 
 
 
 
 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
22 
 
7.4.4 
Product Labeling and Documentation    
OpenBiome’s IB indicates that each sample bottle is labeled with (1) the handling and storage 
warnings, (2) a lot number and (3) the expiration date based on the storage temperature (pictured 
below from left to right). The lot number is formatted as XXXX-YYYY-ZZ, where XXXX is the donor 
number, YYYY is the donation number, and ZZ marks the bottle number. Additionally all donor 
screening results will be provided in the stool shipment. Released placebo units are affixed with 
the same label as active FMP250 units, though the specialized lot numbers will allow for 
differentiation. 
 
 
NOW® Foods brands each Psyllium Husk Powder, Organic plastic bottle with the following label. 
The label provides nutritional facts, suggested usage, ingredients, and a bar code for commercial 
use in addition to other details. The lot number and the expiration date are printed at the bottom 
of each individual unit (not pictured below).  
 
 
 
 
7.5 Product Packaging and Handling 
 
OpenBiome will package investigational and placebo FMP250 units in PET Corning bottles with HDPE 
screw-caps (pictured below). All units will be shipped by overnight carrier in dry ice inside a Styrofoam 
cooler with a WarmMarker temperature indicator attached to the lid. Upon arrival to the Longman 
laboratory, the package will be immediately checked for product tampering and temperature 
exposure. Each unit should be sealed and then stored promptly in a -20 or -80 Celsius degree freezer. 
The seal should not be broken unless the sample is going to be thawed the same day for delivery. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
23 
 
 
 
NOW® Foods packages each Psyllium Husk Powder, Organic product in a white plastic bottle with a 
sealed cap. The bottle is approximately 6.5 inches tall and 3.5 inches wide. Upon arrival to the 
Longman Laboratory, the package will be immediately checked for product tampering and accounted 
for by the Psyllium Tracking Log form. 
 
 
7.6 Product Storage and Stability 
 
Investigational and placebo FMP250 units must be stored in a freezer at all times until directly before 
use. The units are stable for up to 6 months at -20 degrees Celsius or 12 months at -80 degrees Celsius. 
Product stability is not compromised by freezer temperature shifts of up to five degrees Celsius. 
 
NOW® Foods recommends their Psyllium Husk Powder, Organic product be stored in a dry and cool 
place after opening. We assume the same is recommended for its storage at WCMC, before its 
distribution to subjects. 
 
7.7 Product Preparation 
1. Thawing 
a. All FMP250 units must be thawed prior to use by one of the following methods: 
i. 1 hour in a 30-degree Celsius water bath 
ii. 4.5 hours at room temperature 
iii. 16 hours in a refrigerator 
b. Thawed material must be homogenized by mixing for 10 seconds before delivery 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
24 
 
Any leftover FMP250 material must never be reused or refrozen. It should be immediately disposed 
according to internal WCMC/NYPH protocol. 
7.8 Dosing and Administration 
 
7.8.1 
FMP250 
Prior to colonoscopy subjects will be asked to undergo bowel prep and to fast the night before 
the procedure. Additionally, subjects will be provided anti-diarrheal agent(s) 1-2 hours prior to 
the procedure to aid with retention of the fecal transfer, which ideally would be for up to four 
hours.  
 
The study intervention will only be infused through the working channel of the instrument during 
colonoscopy at the day 0 screening visit if the clinician confirms the subject meets the endoscopy 
dependent inclusion criteria. A 250cc dosage of the investigational or placebo FMP250 will be 
delivered in aliquots of 60cc but we also recognize that some fecal material may be lost during 
the transfer. During the week 8 flexible sigmoidoscopy, subjects that were randomized into the 
placebo group will receive a 250cc dose of investigational FMP250 and subjects that were 
randomized into the investigational group will receive a 250cc dose of placebo FMP250.  
 
Once the FMP250 has been thawed, it is stable for administration for up to 4 additional hours at 
room temperature or 8 hours refrigerated. 
 
7.8.2 
Psyllium  
Subjects randomized into the psyllium fiber treatment group will receive two bottles of the 
Psyllium Husk Powder, Organic product to begin consuming three days prior to the day 0 
colonoscopy. They will be asked to take one teaspoon (approximately 5 grams) of this fiber 
supplement twice a day until their week 8 clinic visit which will be approximately 59 days. The 
twice a day dosage is advised to be taken once in the morning (e.g. breakfast) and once in the 
night (e.g. dinner) to help with subject compliance. 
 
NOW® Foods recommends a tablespoon of this product to be mixed in at least a cup of liquid to 
avoid the risk of choking. 
 
7.8.3 
Dosing Delays/Dose Modifications 
 
Not Applicable.  
 
7.9 General Concomitant Medication and Supportive Care Guidelines 
 
All concomitant medications will be recorded and/or updated on subject medication log throughout 
the course of the study and saved in subject binder and REDCap.  
 
7.10 Duration of Therapy and Criteria for Removal from Study 
 
Subjects assigned to the investigational FMP250 treatment groups will receive the FMT once at the 
day 0 colonoscopy and will subsequently receive the placebo FMP250 at week 8 to minimize 
unblinding bias between FMT treatment arms. Subjects assigned to the placebo FMP250 will also 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
25 
 
receive the investigational drug once at the week 8 flexible sigmoidoscopy. The therapy is not given 
over a cycle or extended period of time. 
 
Subjects assigned to the psyllium fiber treatment groups will take the fiber supplement twice daily 
beginning three days prior to the colonoscopy until the week 8 follow-up clinic visit. Subjects who do 
not comply to the recommended dose will not be removed from the study, however, they may not be 
evaluable for scientific analysis for this treatment group. In the case that a subject cannot tolerate the 
fiber supplement due to uncomfortable side effects, we recommend they decrease the dose to one 
teaspoon a day for a week before discontinuing the supplement altogether. Any subject tolerating the 
advised psyllium dose for less than one week will not be considered in this intention to treat trial as 
tolerating intervention, however, they will still continue with the FMT intervention. Importantly, 
subjects will be considered evaluable for scientific analysis in the Fiber + placebo or active FMT 
treatment group if they take the psyllium dosage for at least one-week post-FMT procedure up until 
the 4-week post-FMT clinic evaluation.  
 
Study Termination Guidelines: A subject’s follow-up in the study will end after one of the following 
applies: 
o Subject’s voluntary withdrawal 
o Subject lost to follow-up 
o Subject death 
o Completion of all scheduled study follow-up clinical visits and phone calls 
 
7.11 Duration of Follow Up 
 
Subjects will receive subsequent follow-up phone calls every 6 months for the following year after 
completion from study (in-clinic visits) or until death, whichever occurs first.  Subjects removed from 
study for unacceptable adverse events will be followed by the treating clinician and/or principal 
investigator until resolution or stabilization of the adverse event. 
 
7.12 Measures to Minimize Bias: Randomization and Blinding  
 
 
Randomization Bias: 
A series of randomized blocks of fixed size will be generated with a 1:1:1 allocation ratio. This 
will provide assurance that after a given block as completed subject enrollment, there will be 
the same number of subjects assigned to each of the three study arms. Only the statistician and 
the study coordinator will have access to the randomization list. The dedicated research 
coordinator will assign the randomization code from the list for each subsequently enrolled 
patient (i.e., the statistician will give the list that contains the randomized blocks only to the 
research assistant).  
 
Unblinding Bias: 
Clinicians are blinded while they assess the clinical response at week 8 and will be unblinded only 
once all clinical evaluations at week 8 have been conducted for all 135 study participants. This will 
reduce the risk of potential bias by the clinician as all treatment groups will receive treatment 
(blinded investigational or placebo FMP250) at week 8 by flexible sigmoidoscopy.  
 
Unblinding in the case of emergency (i.e. anticipated or unanticipated serious adverse event) is 
up to the discretion of the treating physician, particularly if it is medically necessary to know what 
treatment assignment the subject received. However, it is advised that the treating physician 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
26 
 
discuss with the principal investigator prior to breaking protocol. The study coordinator will not 
delay or refuse unblinding if knowledge of the investigational drug is imperative for emergency 
treatment. The study coordinator will then immediately notify the PI of unblinding and will 
document the reason in the subject’s folder and/or eCRF.  
 
7.13 Study Intervention/Follow-up Compliance 
Adherence to the protocol can be assessed and verified from logs, such as eligibility checklists and 
standard operating procedures (SOPs), that will be created by study coordinators and confirmed by 
the treating clinician throughout the course of the intervention. These logs will be based on the 
schedule of events detailed in Section 6.1, Table 1. to ensure the subject’s compliance and that all 
data collection is successfully completed and reviewed at each visit. These paper forms will be stored 
in each subject’s study binder.  
 
In our previous pilot study, we also utilized single colonoscopic delivery of FMP250 and did not 
experience any loss to follow up due to our short-term follow-up clinic evaluation at 4 weeks post-
FMT. Therefore, we anticipate our loss to follow-up rate to remain consistent in this new clinical trial. 
Considering patients will be blinded up until all study subjects complete week 8 evaluations, we expect 
them to comply with our follow-up clinic visits because the subject would want to ensure they 
received the investigational drug. However, if a patient does not respond after three contact attempts 
(either phone call and/or e-mail) by the study coordinator they will be labeled as a lost to follow-up.  
 
In regard to safety-phone calls at 6-months and 1-year, subjects will be contacted three times (either 
phone call and/or e-mail). Should subject fail to answer, the investigator or designee will mail a 
certified letter to the subject’s last known mailing address in order to regain contact. 
 
8. Study Intervention Discontinuation and Participant Discontinuation/Withdrawal 
 
8.1 Discontinuation of Study Intervention 
 
Discontinuation from receiving FMP250 does not mean discontinuation from the study, and remaining 
study procedures should be completed as indicated by the study protocol.  If a clinically significant 
finding is identified (including, but not limited to changes from baseline) after enrollment, the 
investigator or qualified designee will determine if any change in participant management is needed. 
Any new clinically relevant finding will be reported as an adverse event (AE). Certain AE/SAEs may 
result in a safety review and may cause for the discontinuation of the study intervention. See Section 
15.2. for details on halting rules. 
 
Discontinuation of Psyllium Husk Powder, Organic during the approximately eight-week course does 
not translate to discontinuation from this study. Any subject tolerating the advised psyllium dose for 
less than one week will not be considered as tolerating intervention, however, they will still continue 
with the FMT intervention. Therefore, the remaining study procedures should be completed as 
indicated in the study protocol. Further details on what to do if a subject does not finish the complete 
fiber supplement course can be found in Section 7.10. 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
Reason for discontinuation (escalation of care, not feeling well, surgery, etc.)  


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
27 
 
• 
All follow-up evaluations (AE/SAE reporting via phone calls, clinic visits) detailed in Section 
13.   
8.2 Participant Discontinuation/Withdrawal from the Study 
Subjects are free to withdraw from participation in the study at any time upon notification. However, 
if a subject decides to stop participating in the study we encourage them to speak with the research 
coordinator or investigator first.  
 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
• 
Pregnancy 
• 
Significant study intervention non-compliance  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the best 
interest of the participant 
• 
Disease progression which requires discontinuation of the study intervention 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
• 
Participant lost to follow-up after several attempts to contact subject to schedule study visit. 
 
Patients withdrawn because of SAEs, AEs or at the discretion of the physician will continue to receive 
treatment in accordance with current standard of care.  Patients having AEs will be monitored with 
relevant clinical assessments, laboratory tests, imaging studies and procedures as determined by the 
treating physician. 
The date and reason for participant discontinuation or withdrawal from the study will be recorded on 
an electronic Case Report Form (eCRF) created on REDCap. Subjects who sign the informed consent 
form and are randomized but do not receive the study intervention may be replaced.  Subjects who 
sign the informed consent form, and are randomized and receive the study intervention, and 
subsequently withdraw, or are withdrawn or discontinued from the study, will not be replaced. 
 
8.3 Lost to Follow Up 
A participant will be considered lost to follow-up if he or she fails to return for 1 scheduled visits and 
is unable to be contacted by the study site staff. Every reasonable effort will be made to contact these 
patients to ensure they are receiving appropriate follow up care with documentation of any serious 
adverse effects (SAEs), adverse effects (AE) or changes in medical condition (for example, Mayo 
score), diagnoses or medications. 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit within 1 week 
and counsel the participant on the importance of maintaining the assigned visit schedule and 
ascertain if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local equivalent 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
28 
 
methods). These contact attempts should be documented in the participant’s medical record 
or study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
9. Correlative/Special Studies  
 
9.1 Laboratory Correlative Studies 
 
9.1.1 
Microbiome – Laboratory Correlative Study #1 
 
9.1.1.1 Collection of Specimen(s):  Fecal 
 
9.1.1.2 Handling of Specimen(s): Frozen -80C 
 
 
9.1.2 
Lamina propria cells – Laboratory Correlative Study #2 
 
9.1.2.1 Collection of Specimen(s):  Biopsy 
 
9.1.2.2 Handling of Specimen(s): Collected in PBS, Processed in Longman lab 
 
9.1.3 
Peripheral Blood – Laboratory Correlative Study #3 
 
9.1.3.1 Collection of Specimen(s):  Blood sample 
 
9.1.3.2 Handling of Specimen(s): Processed in Longman lab 
 
9.2 Special Studies 
 
9.2.1 
Special Correlative Study #1 
 
 
 
9.2.1.1 Assessment 
Microbial alterations, transferability and engraftment will be studied by sequencing DNA 
material at different timepoints. Previous studies have used reference genome 
alignments to evaluate microbial engraftment, however this approach does not 
determine taxonomy at the strain level, and therefore it is less accurate in defining the 
shared microbes between donor and patient. To overcome this issue metagenomics post-
quality control sequences will be profiled using StrainPhlAn pipeline. To determine the 
degree of the engraftment, we will apply principal coordinates analysis to Bray-curtis 
distances. Wilcoxon signed-rank (paired) statistical tests will be used to evaluate the level 
of microbial similarity (Bray-curtis) between donor, pre-FMT and post-FMT. Given the 
dissimilar microbial composition observed in donor and pre-FMT samples in our 
preliminary data, we propose to use these microbial signatures to infer the origin of the 
post-FMT microbes. Briefly, bacteria shared among donor and pre-treatment samples will 
be removed from the model and the remained unique strains will be calculated. Machine 
learning models, Random Forest procedure, will be fitted in R-studio to predict bacterial 
engraftment and their persistence, as previously described.  
9.2.2 
Special Correlative Study #2 
 
 
 
9.2.2.1 Assessment 
Lamina propria mononuclear cells (LPMCs) are the key effectors within the mucosa.  
Numerous studies have characterized the contribution of bacterial signals to the effector 
functions of LPMCs, but the signatures associated with prebiotic supplementation are 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
29 
 
limited.  To characterize these profiles as we have done previously, LPMCs will be purified 
from digested endoscopic biopsy tissue and cryopreserved.  We have optimized 
processing and freezing conditions to allow for efficient recovery and immune 
phenotyping by flow cytometry. These samples will then be used to phenotype innate and 
adaptive lymphocyte effector cell function.  In addition, to profiling CD4+ T cell subsets 
by transcription factor (RORt, T-bet, GATA-3, FoxP3) and intracellular cytokine 
production (IFN, IL-4, IL-17, IL-22), CD8+ T cells from the lamina propria and intra-
epithelial lymphocyte fraction will be profiled. 
 
10.  Measurement of Effect  
 
10.1 Response Criteria 
 
 
10.1.1 Primary Endpoint Assessments  
10.1.1.1 Mayo Scoring System30  
The Mayo Scoring System will be used for the assessment of ulcerative colitis activity. It 
is a composite score that ranges from 0-12 based on the following four categories: 
bleeding, stool frequency, physician assessment, and endoscopic findings. A partial Mayo 
Score ranges from 0-9 and can also be utilized if no endoscopic visualization is available 
to assess disease activity. 
Study subjects will be evaluated by a full Mayo score at day 0 and week 8, and a partial 
Mayo score at the week 4 clinic visit. Both clinical response and remission will be 
evaluated at week 8 post-FMT. Clinical response is described as a reduction of the Mayo 
score by >3 points and >30% reduction from baseline with an accompanying decrease in 
the sub-score for rectal bleeding of at least 1 point. Clinical remission will be defined by 
Mayo score ≤ 2 without any sub-score >1, and Mayo endoscopic sub-score 0-1. 
Table 2. Mayo Scoring System for the assessment of ulcerative colitis activity.  


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
30 
 
 
 
10.1.2 Secondary Endpoint Assessments  
 
10.1.2.1 Biomarkers 
Blood, stool, and mucosal samples will be processed and analyzed in the Longman 
Laboratory. The schedule and frequency of these collections are present in the Table of 
Events (Table 1). The total amount of blood collected for biomarker and safety evaluations 
will be specified in the Informed Consent Form.  
10.1.2.2 Adverse Event Reporting 
See Section 13 for more information on AE and/or SAE reporting for safety evaluation. 
 
10.2 Duration of Response  
 
 Not applicable. 
 
10.3 Progression-Free Survival  
 
Not applicable. 
 
10.4 Other Response Parameters 
 
See Section 12.4 for a description of all other study endpoints. 
 
11. Data Reporting / Regulatory Considerations 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
31 
 
11.1 Data Collection 
 
The data collection plan for this study is to utilize REDCap to capture all treatment, toxicity, efficacy, 
and adverse event data for all enrolled subjects.  
 
11.1.1 REDCap 
 
REDCap (Research Electronic Data Capture) is a free data management software system that is 
fully supported by the Weill-Cornell Medical Center CTSC.  It is a tool for the creation of 
customized, secure data management systems that include Web-based data-entry forms, 
reporting tools, and a full array of security features including user and group-based privileges, 
authentication using institution LDAP system, with a full audit trail of data manipulation and 
export procedures.  REDCap is maintained on CTSC-owned servers that are backed up nightly and 
support encrypted (SSL-based) connections.  Nationally, the software is developed, enhanced and 
supported through a multi-institutional consortium led by the Vanderbilt University CTSA. 
 
11.2 Regulatory Considerations 
 
11.2.1 Institutional Review Board/Ethics Committee Approval  
 
As required by local regulations, the Investigator will ensure all legal aspects are covered, and 
approval of the appropriate regulatory bodies obtained, before study initiation.  
Before initiation of the study at each study center, the protocol, the ICF, other written material 
given to the patients, and any other relevant study documentation will be submitted to the 
appropriate Ethics Committee. Written approval of the study and all relevant study information 
must be obtained before the study center can be initiated or the IP is released to the Investigator. 
Any necessary extensions or renewals of IEC/IRB approval must be obtained for changes to the 
study, such as amendments to the protocol, the ICF, or other study documentation. The written 
approval of the IEC/IRB together with the approved ICF must be filed in the study files.  
The Investigator will report promptly to the IEC/IRB any new information that may adversely 
affect the safety of the patients or the conduct of the study. The Investigator will submit written 
summaries of the study status to the IEC/IRB as required. On completion of the study, the IEC/IRB 
will be notified that the study has ended.  
 
Neither the Investigator nor BMS will modify or alter this protocol without the agreement of the 
other. All agreed protocol amendments will be clearly recorded on a protocol amendment form 
and will be signed and dated by the original protocol approving signatories. All protocol 
amendments will be submitted to the relevant institutional IEC/IRB for approval before 
implementation, as required by local regulations. The only exception will be when the 
amendment is necessary to eliminate an immediate hazard to the trial participants. In this case, 
the necessary action will be taken first, with the relevant protocol amendment following shortly 
thereafter.  
Once protocol amendments or consent form modifications are implemented at the lead site, Weill 
Cornell Medicine, updated documents will be provided to participating sites. Weill Cornell 
Medicine must approve all consent form changes prior to local IRB submission.  


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
32 
 
Relevant study documentation will be submitted to the regulatory authorities of the participating 
countries, according to local/national requirements, for review and approval before the beginning 
of the study. On completion of the study, the regulatory authorities will be notified that the study 
has ended.  
 
11.2.2 Ethical Conduct of the Study  
The Investigators and all parties involved should conduct this study in adherence to the ethical 
principles based on the Declaration of Helsinki, GCP, ICH guidelines and the applicable national 
and local laws and regulatory requirements.  
 
This study will be conducted under a protocol reviewed and approved by the applicable ethics 
committees and investigations will be undertaken by scientifically and medically qualified 
persons, where the benefits of the study are in proportion to the risks. 
 
11.2.3 Informed Consent 
 
The investigator or qualified designee must obtain documented consent according to ICH-GCP 
and local regulations, as applicable, from each potential subject or each subject’s legally 
authorized representative prior to participating in the research study. Subjects who agree to 
participate will sign the approved informed consent form and will be provided a copy of the signed 
document.   
 
The initial ICF, any subsequent revised written ICF and any written information provided to the 
subject must approved by IRB prior to use. The ICF will adhere to IRB/IEC requirements, applicable 
laws and regulations. 
 
11.2.4 Compliance with Trial Registration and Results Posting Requirements  
 
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the Food 
and Drug Administration Amendments Act (FDAAA), the Sponsor-Investigator of the trial is solely 
responsible for determining whether the trial and its results are subject to the requirements for 
submission to http://www.clinicaltrials.gov. Information posted will allow subjects to identify 
potentially appropriate trials for their disease conditions and pursue participation by calling a 
central contact number for further information on appropriate trial locations and trial site contact 
information. 
 
11.2.5 Record Retention 
 
Essential documents are those documents that individually and collectively permit evaluation of 
the study and quality of the data produced.  After completion of the study, all documents and 
data relating to the study will be kept in an orderly manner by the Investigator in a secure study 
file.  Essential documents should be retained for 2 years after the final marketing approval in an 
ICH region or for at least 2 years since the discontinuation of clinical development of the IP. In 
addition, all subjects’ medical records and other source documentation will be kept for the 
maximum time permitted by the hospital, institution, or medical practice.   
 
12. Statistical Considerations 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
33 
 
 
12.1 Sample Size and Analysis Plan 
Prior studies and clinical experience involving FMT suggests a 27% response rate from a null rate of 
diet alone at 7%. Based on previous work18, we estimate the effect size of clinical response to 
FMT+fiber in patients with IBD to be approximately double the FMT-alone group (i.e., 55% vs. 27%, 
respectively). Recruitment of ~135 subjects with 45 patients per arm was calculated assuming a 55% 
response rate at 8 weeks in the FMT+fiber arm and a 27% response rate at 8 weeks in the FMT-alone 
arm, with approximately 80% power to detect this difference (using a two-sided significance level of 
0.05)31. We will conduct pairwise chi-square analysis between the study arms of interests to directly 
address the primary study objective to detect a difference in clinical response (i.e. FMT+ fiber versus 
FMT alone). The remaining two pairwise comparisons can be considered as secondary aims and thus 
no multiple comparison adjustment is needed.  
Considering analyses will be performed based on intent to treat, any subject in the FMT alone (no 
psyllium) or the FMT with psyllium intervention groups with missing primary endpoint data at week 8 
will be labeled as failed treatment (no change in clinical response from baseline). Therefore, subjects 
with missing data will have their baseline Mayo score carried forward to remain the same for the 
week 8 primary endpoint. For primary efficacy analysis, the populations FMT + psyllium vs. FMT alone 
(no fiber) will be compared by the chi-square test (pair-wise group comparisons will also be 
performed). Those characteristics found to be clinically different between groups at baseline using 
significance criteria of p<0.05 or known to be clinically important (e.g., in the event randomization 
provided insufficient balance between groups) will be incorporated into a multivariable logistic 
regression model of clinical response (i.e., binary outcome variable). This will facilitate estimating the 
independent effect of treatment group status on clinical response, after controlling for such factors, 
if any, that may differ between the two study arms at baseline. Sensitivity analyses for the primary 
endpoint will also be performed; in addition to carrying forward the baseline Mayo score for subjects 
with missing data at week 8, the minimum, median, and maximum Mayo score of subjects with 
available data at week 8 will be used (imputed) for subjects with missing data at week 8. Similarly, we 
will also explore multiple imputation techniques under varying assumptions of missingness (e.g., 
missing completely at random and missing at random). These multiple imputation techniques will rely 
on regression models to predict the missingness and missing values, and incorporate uncertainty 
through an iterative approach. For dealing with the possibility of data not missing at random, a worst-
case analysis will be explored (i.e., missing data are replaced with the “worst” value under the not 
missing at random [non-ignorable] assumption). These sensitivity analyses will allow for an 
assessment of the consistency of the primary endpoint difference between groups under the varying 
assumptions for missing data at week 8. 
Similar analyses will be conducted for secondary and exploratory endpoints (i.e., need for escalation, 
clinical remission, etc.). For secondary efficacy and safety analysis, comparison populations include: 
(i) FMT alone (no fiber) vs. placebo FMT alone (no fiber); (ii) FMT (with or without fiber) vs. placebo 
FMT (with or without fiber); (iii) placebo FMT with fiber vs. placebo FMT alone (no fiber); (iv) FMT 
with fiber vs. placebo FMT with fiber. All p-values will be two-sided with statistical significance 
evaluated at the 0.05 alpha level.  Ninety-five percent confidence intervals for all parameters of 
interest will be calculated to assess the precision of the obtained estimates. Secondary analysis 
excluding subjects who discontinued the study treatment for reasons clearly not related to the study 
medications will also be performed. Treatment groups will be assessed at baseline with primary 
objective criteria. Balance between treatment groups will be assessed by ANOVA tests or Kruskal-
Wallis tests for continuous variables and chi-square tests or Fisher’s exact tests for categorical 
variables. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
34 
 
12.2 Sample Size/Accrual Rate 
 
We anticipate approximately 150 patients to be screened for inclusion into our study, however, 15 
will likely be screening failures or dropouts. Therefore, we propose a sample size of N=135. We 
anticipate to accrue approximately 30-50 subjects/year over the course of our 4-year study duration.  
 
12.3 Stratification Factors  
. 
Not applicable. 
 
12.4 Analysis of Endpoints 
 
12.4.1 Analysis of Primary Endpoints  
1. Clinical response at week 8 post-FMT, as defined by the reduction of the Mayo scoring 
system by >3 points (+30% reduction) with an accompanying decrease in the sub-score 
for rectal bleeding of at least 1 point (Section 10.1.2.2). 
12.4.2 Analysis of Secondary Endpoints  
a. Clinical remission at week 8 post-FMT, as defined by Mayo score ≤ 2 without any sub-
score >1 
b. Endoscopic response or remission, as defined as a Mayo endoscopic sub-score 0-1 with 
at least a 1-point reduction from baseline or a Mayo endoscopic sub-score of 0 
c. Safety will be assessed by: 
1. 
Subject mucosal biopsies, stool and blood testing.  
2. 
Subject symptomatology via medical interview, physical exam, and Mayo 
score and change in standard UC medications.  
3. 
Number and type of treatment related adverse events 
4. 
Number and type of disease-related complications such as hospitalizations, 
surgeries and endoscopies, medical complications, and mortality. 
12.4.3 Analysis of Exploratory Endpoints 
1. Alterations in microbial profiles as defined by sequence of genetic material from fecal 
material  
a. Sample collection  
1. Up to 60cc of the recipient stool will be collected at the time of 
procedure. 
2. Up to 60cc of recipient stool will be collected at 4 and 8 weeks of follow 
up (as per protocol).  
3. Samples will be aliquoted and stored at -80C for batched analysis.  
b. Sequencing 
1. Fecal DNA extraction  
1. Fecal DNA will be extracted via phenol chloroformor, a commercially 
available resin binding column. 
2. DNA will be stored at -80C until sequencing.  
3. 16S rRNA amplicon libraries will be prepared for analysis by Illumina 
MiSeq or HiSeqor Roche 454 high throughput sequencing. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
35 
 
4. Genomic DNA libraries will be prepared using Illumina library 
preparation for sequencing on Illumina MiSeq or HiSeq. 
5. Metabolomic analysis by mass spectrometry 
6. Microbial strains will be isolated for genomic and functional analysis 
in vitro and in mouse models  
2. Alterations in immune cell function from mucosal biopsies as defined by RNA 
sequencing and flow cytometry 
a. Sample collection: 4 biopsies will be collected into sterile saline for cellular analysis 
b. Biopsy will be removed of IEL fraction with dithiothreitol (DTT) followed by EDTA.  
Remaining tissue will be digested with collagenase and DNase and purified over a 
discontinuous percoll gradient to obtained lamina propria mononuclear cells. 
a. Stimulated and unstimulated will be analyzed by flow cytometry, 
transcriptional regulation, and cytokine production (including ELISA, 
cytometric bead array, or Luminex). 
c. Biopsy will be transferred to DNA extraction buffer and mechanically homogenized.  
Total DNA will be extracted by phenol chloroform as above.  16S library preparation 
and sequencing will be performed to determine mucosal associated bacteria 
12.5 Interim Analysis 
 
No interim analysis will be conducted for this study.  
 
 12.6 Reporting and Exclusions 
 
12.6.1 Evaluation of Toxicity 
 
All subjects will be evaluable for toxicity from the time of their first treatment with FMP250.  
 
12.6.2 Evaluation of Response 
 
All subjects included in the study will be assessed for response to treatment if they meet all 
inclusion and exclusion criteria, and then receive either placebo or investigational FMP250 
treatment during the screening colonoscopy.   
 
13. Adverse Event Reporting Requirements  
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial. The investigator will 
be required to provide appropriate information concerning any findings that suggest significant hazards, 
contraindications, side effects, or precautions pertinent to the safe use of the drug or device under 
investigation.  Safety will be monitored by evaluation of adverse events reported by subjects or observed 
by investigators or research staff, as well as by other investigations such as clinical laboratory tests, x-rays, 
electrocardiographs, etc. 
 
13.1 Adverse Event Definition 
 
An adverse event (also referred to as an adverse experience) is any untoward medical occurrence in 
a patient or clinical trial subject administered FMT that does not necessarily have to have a causal 
relationship with this treatment. It can be any unfavorable and unintended sign (e.g., an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a FMT but does not 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
36 
 
imply any judgment about causality. An adverse event can arise with any use of FMP250 (e.g., off-
label use, use in combination with another drug) and with any route of administration, formulation, 
or dose, including an overdose.  
 
 
13.1.1 Investigational Drug, FMP250, Risks (Potential Adverse Events) 
 
There may be risks for this therapeutic intervention which will be discussed with study participant by 
the research doctor. Risks from donor stool, such as serious blood-stream infection (rare) or fevers, 
abdominal cramping, bloating, diarrhea, and bloody stool (less likely). The potential risks associated 
with FMP250 may include but are not limited to the following: 
• 
Transmission of infectious organisms (bacterial, viral, fungal) contained in the stool 
o Multi-Drug Resistant Organisms (MDROs) 
▪ 
A potential risk of fecal microbiota transplantation (FMT) is the 
transmission of antibiotic-resistant bacteria. These are bacteria that are 
resistant to some antibiotics. These bacteria could be transmitted 
through FMT and could cause serious infection or death. 
▪ 
The study drug, FMP250, that will be delivered by FMT is provided by 
OpenBiome, a universal stool bank where donors who provide stool for 
FMT undergo regular screening for certain antibiotic-resistant bacteria. 
Each FMT is only made available when these screens do not detect 
antibiotic-resistant bacteria in the donor before and after the stool 
donation. Donors also undergo regular clinical assessments for any risk 
factors associated with carrying antibiotic-resistant bacteria, such as 
recent use of antibiotics, visiting certain healthcare facilities, or certain 
travel activities. 
o Shiga Toxin-Producing E. Coli (STEC) and Enteropathogenic E. Coli (EPEC)  
▪ 
A potential risk of fecal microbiota transplantation (FMT) is the 
transmission of STEC and EPEC. STEC is a type of E. coli that can produce 
a toxin called Shiga toxin. Shiga toxin can be transmitted through FMT 
and can cause symptoms like abdominal pain, diarrhea (often bloody), 
vomiting, and mild fever. Most people develop symptoms within 3-4 days 
of acquiring the bacteria, and most get better within 5-7 days. EPEC is 
another type of E. coli that can be transmitted through FMT and is 
generally carried asymptomatically but can sometimes cause transient 
watery diarrhea, similar to traveler’s diarrhea. Symptoms typically 
resolve in a matter of days. 
▪ 
The study drug, FMP250, that will be delivered by FMT is provided by 
OpenBiome, a universal stool bank where donors who provide stool for 
FMT undergo regular screening for these bacteria. Each FMT is only made 
available to delivery when these stool screenings do not detect EPEC or 
STEC in the donor before and/or after the stool donation.  
o SARS-CoV-2 Infection 
▪ 
A potential risk of fecal microbiota transplantation (FMT) is the 
transmission of SARS-CoV-2, a novel coronavirus that causes the disease 
COVID-19. Infection with SARS-CoV-2 may be transmitted through stool 
and may cause serious illness or death. It is possible for healthy, 
asymptomatic stool donors to potentially be infected with SARS-CoV-2. 
▪ 
The FMT you will receive is provided by OpenBiome, a universal stool 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
37 
 
bank where donors who provide stool for FMT undergo regular stool, 
blood, and nasal screenings for many different infectious agents, 
including SARS-CoV-2, the virus that causes the illness called COVID-19. 
However, not all infectious agents are screened for and some infectious 
agents are as yet undiscovered. Each FMT unit is only made available for 
use when these screens do not detect the infectious agents for which we 
test. Donors also undergo regular in-person clinical assessments for any 
risk factors, including risk factors associated with carrying SARS-CoV-2, 
such as visiting certain healthcare facilities, or other behaviors that may 
increase the risk of exposure. However, because COVID-19 is so 
widespread, donors may be exposed or infected without having an 
identified risk factor for exposure. They may also have no symptoms of 
infection. OpenBiome continually updates its screening guidelines and 
procedures as additional data, tests, and information become available.If 
the FMT that you receive was made from stool donated after December 
1st, 2019, the stool donor was tested for the presence of SARS-CoV-2 
using a nasopharyngeal swab to conduct a viral RNA test. This kind of test 
looks for the specific genetic material that makes up the virus. If a donor 
tests positive for SARS-CoV-2, OpenBiome destroys any FMT units made 
from that donor in the 4 weeks (28 days) before their positive test result. 
The donor is also disqualified from providing stool donations for at least 
8 weeks. To be re-instated in the stool donation program after 8 weeks, 
the donor must pass all screens. Although we cannot be absolutely 
certain, it is unlikely that SARS-CoV-2 is present in stool donations that 
were provided to OpenBiome on or prior to December 1st, 2019. For this 
reason, testing on donors prior to December 1st has not been performed. 
Though these precautions are taken to minimize the risk of SARS-CoV-2 
transmission via FMT, the scientific and clinical community continues to 
learn more about SARS-CoV-2 and COVID-19. There are limits to the 
detection levels of laboratory tests, including those for SARS-CoV-2. Even 
with current screening and testing strategies, there may be additional 
risks that are unknown at this time. Although the donor screening tests 
we perform are likely to prevent you from receiving FMT from a donor 
who is infected with SARS-CoV-2, we cannot be absolutely certain that 
the stool you receive has not been contaminated with the SARS-CoV-2 
virus. 
o Monkeypox Infection 
▪ 
A potential risk of fecal microbiota transplantation (FMT) is the 
transmission of monkeypox. Infection can cause symptoms including 
rash, fever, fatigue, myalgia, and respiratory symptoms which may be 
severe especially in immunocompromised patients. Studies have 
documented the presence of monkeypox virus DNA in rectal swabs 
and/or stool from infected individuals, but it is unknown whether 
monkeypox can be transmitted through stool or from asymptomatic 
infected individuals.  
• 
Missed polyps, cancer, or other lesion (infusing donor stool interferes with visualization 
of colonic mucosa) 
• 
Allergic reaction to antigens in donor stool 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
38 
 
• 
Enhanced ulcerative colitis activity 
• 
Theoretical increased risk of developing disease which may be related to donor gut 
bacteria (i.e. obesity, metabolic syndrome, autoimmune conditions, allergic/atopic 
disorders, neurologic disorders, and/or malignancy) 
 
Many side effects go away shortly after the stool transplant is stopped, but in some cases side effects 
can be serious, long lasting or permanent. In reported experiments of subjects treated with FMT 
via colonoscopy no adverse effects were noted.   
 
13.1.2 FMT Procedural Risks (Potential Adverse Events) 
 
Based on the existing literature and the investigator’s previous experience, the risks from FMT 
and dietary supplement ingestion are low. The usual risks of performing colonoscopy and flexible 
sigmoidoscopy still apply, as well as the minor risk associated with additional tissue biopsy 
procurement during flexible sigmoidoscopy and colonoscopy. These procedures are overall safe 
with few complications. Risks and side effects related to the delivery procedure include: 
1. The risks of standard lavage include dehydration and minor electrolyte imbalances.  
2. Standard colonoscopy and sigmoidoscopy include the risk of bowel perforation, bleeding, 
and adverse cardiopulmonary events related to sedation. (serious but less likely) 
3. Many adverse effects of colonoscopy and sigmoidoscopy resolve shortly after the 
procedure has been completed, but in some cases abdominal discomfort and gaseous 
pain can persist for several hours. (common but mild) 
4. Risks related to sedation. (less likely) 
There may also be unpredictable side effects, other than listed above that. Other drugs may be given 
to make side effects that occur less serious and less uncomfortable.  
 
13.1.3 Risk from colonoscopy and sigmoidoscopy (Potential Adverse Events) 
 
Risks from colonoscopy and sigmoidoscopy include perforation (serious but less likely), abdominal 
discomfort during or after the procedure (common but mild), and risks related to sedation (less 
likely). The incidence of risk associated with biopsies taken as standard of care does not increase 
with additional biopsies taken for research. These risks include bleeding, intestinal perforation, 
and / or infection. Bleeding associated with biopsy generally resolves spontaneously, however, in 
the unlikely event of persistent bleeding, clips and / or cautery can be applied to stop the bleeding. 
 
13.1.4 Risk from Medical Record Review (Potential Adverse Events) 
 
Subjects will be asked about their medical history, usage of birth control, concurrent medication. 
There is a risk associated with the loss of privacy or confidentiality due to the probing of 
information. For example, if your identity as a participant in this study or your identifiable health 
information were disclosed to unauthorized persons, there is the possible risk of discrimination 
by employers or insurance providers. 
 
13.1.5 Risk from Blood Draws (Potential Adverse Events) 
 
Drawing blood from a vein may cause local pain, bruising, occasional lightheadedness, fainting, 
and very rarely, infection at the site of the blood draw. Rarely, blood clots may form and infections 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
39 
 
may occur. If you feel faint, you should lie down right away to avoid falling down. You should let 
your study doctor or staff know if you have any of these problems. 
 
13.1.6 Risk from Placebo (Potential Adverse Events) 
 
In this research study, you may receive a placebo (inactive substance). If you receive the 
placebo, your condition may not change or may worsen. 
 
13.1.7 Risk from Psyllium Husk (Potential Adverse Events) 
 
The main concern with psyllium husk is the risk of choking, specifically if the product is not 
consumed with sufficient liquid. Our research physicians also hypothesize bloating may occur. The 
following rare side effects may be of concern for older adults: abdominal discomfort, nausea, mild 
abdominal cramps, griping, and faintness. 
 
 13.1.8 Risk from Anti-Diarrheal Agents (Potential Adverse Events) 
 
Healthy adults usually don’t experience side effects from antidiarrheal medicines. But side effects 
may be a concern if you are older or have health problems. Side effects of diphenoxylate/atropine 
may include: drowsiness, dizziness, headache, tiredness, restlessness, blurred vision, dry mouth, 
nausea, vomiting, upset stomach, loss of appetite, skin rash, or itching. Unlikely but serious side 
effects of diphenoxylate/atropine including: stomach or abdominal pain or swelling, severe 
nausea or vomiting, mental/mood changes (e.g., confusion, depression), or numbness and tingling 
of arms or legs. Side effects of loperamide may include:  dizziness, drowsiness, tiredness, 
constipation, stomach pain, skin rash, or itching. Unlikely but serious side effects may also include 
severe constipation/nausea/vomiting, stomach or abdominal pain, or uncomfortable fullness of 
the stomach or abdomen. 
 
There may also be side effects, other than listed above that we cannot predict. Other drugs may 
be given to make side effects that occur less serious and less uncomfortable. Many side effects go 
away shortly after the stool transplant is stopped, but in some cases side effects can be serious, 
long lasting or permanent 
 
13.1.9 Risk for Women of Child-Bearing Potential 
 
Participation in this the study may involve unknown risks to a pregnant woman, unborn baby or 
nursing infant. Subjects must not take part in this study if they are pregnant, plan to become 
pregnant during the research study period, or are breast-feeding a baby. 
 
What do subjects need to know about reproductive health and/or sexual activity if they are in this 
study? 
 
If a subject is sexually active, both men and women should use at least one effective 
means of birth control while participating in this research study. According to the World 
Health Organization and the United States Center for Disease Control and Prevention, the 
most effective forms of birth control include complete abstinence, surgical sterilization 
(both male and female), intrauterine devices (IUDs), and the contraceptive implant. The 
next most effective forms of birth control include injectables, oral contraceptive pills, the 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
40 
 
contraceptive ring, or the contraceptive patch. Acceptable, but least effective, methods 
of birth control include male condoms (with or without spermicide) and female condoms. 
 
If a subject becomes pregnant while participating in this research study, it is important 
that they tell the study doctor or other research team member immediately. The subject 
will be required to stop receiving study procedure/intervention for this study; however, 
other clinical care options will be discussed with them at that time if necessary and they 
will continue to complete the AE phone calls, week 4 clinic visit, and week 12 clinic visit 
as originally planned. The only difference will be that your week 8 assessment will be 
changed from a standard of care flexible sigmoidoscopy procedure into a clinic visit. This 
means you will do all other assessments, such as standard of care labs, research collection 
of blood and stool, physical exam, vital signs, height and weight measurements, etc. 
Therefore, the week 8 will no longer include a procedure, FMT blinded treatment, and 
biopsy collection for standard of care or research. 
 
If a subject is considered to be postmenopausal, they are not required to use 
contraception while participating in this research study. Postmenopausal women rarely 
become pregnant.  
 
13.1.10 Likelihood of Any Adverse Event 
1. Very Likely 
a. Mild to moderate abdominal pain or gaseous discomfort during or after 
colonoscopy 
b. Fatigue on the day of the colonoscopy from sedatives 
c. Pain, bruising, feeling faint or slight risk of infection from blood draws 
2. Less Likely 
a. Nausea with possible vomiting from ingestion of the standard lavage 
3. Less Likely but Serious 
a. Transmission of infection from donor specimen 
b. Allergic reaction to unknown antigen present in donor stool 
c. Risks and side effects related to the colonoscopy or follow-up sigmoidoscopy 
including bleeding, bowel perforation and adverse cardiopulmonary events 
related to sedation 
d. Acquisition of antibiotic resistance or risk factors for chronic diseases such as 
diabetes, inflammatory bowel disease, obesity, or colon cancer 
 
13.1.11 Adverse Event Characteristics and Related Attributions 
 
CTCAE term (AE description) and grade:  The descriptions and grading scales found in the 
revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized 
for AE reporting in this study and reported to the primary investigator as frequently as adverse 
events occur.  A copy of the CTCAE version 5.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov). 
 
• 
Attribution of the AE: 
- Definite – The AE is clearly related to the study treatment. 
- Probable – The AE is likely related to the study treatment. 
- Possible – The AE may be related to the study treatment. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
41 
 
- Unlikely – The AE is doubtfully related to the study treatment. 
- Unrelated – The AE is clearly NOT related to the study treatment. 
 
 
 
13.1.12 Recording of Adverse Events 
 
All AEs, regardless of seriousness, severity, or causal relationship to FMT, will be recorded in the 
subject’s medical record and/or subject specific AE log. The AE log will be maintained by the 
research staff and kept in the subject’s research chart.     
 
13.1.13 Reporting of AE to WCM IRB 
 
All AEs occurring on this study will be reported to the IRB according to the IRB policy, which can 
be accessed via the following link:  
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting_Poli
cy.pdf.  
 
13.1.14 Reporting of AE to FDA  
The following AEs will be specifically documented and reported to FDA within 15 calendar days if 
considered unexpected*: 
1. Complications related to the colonoscopy, including sedation, perforation, or bleeding 
2. Complications related to FMT (infection, inflammatory or allergic reactions) 
3. Solicited and unsolicited AEs assessed via follow up telephone calls and clinic visits  
4. Development of new symptoms or diagnoses (for example, irritable bowel syndrome, 
inflammatory bowel disease (IBD), autoimmune disorder, neurologic disorder) which may 
be related or unrelated to FMT will be elicited at follow-up calls and visits, documented 
and reported to the FDA 
* According to the FDA, an AE is considered “unexpected” if it is not listed in the investigator 
brochure or is not listed at the specificity or severity that has been observed; or, if an 
investigator brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application, as 
amended. 
 
13.1.15 Reporting Events to Participants 
 
Based on our pilot study and the Investigator’s Brochure by OpenBiome, all anticipated SAEs and 
AEs will be listed and made known to the subject in the informed consent. Any additions and/or 
changes to the list of potential SAEs or AEs will require an update of the informed consent to be 
approved by the IRB. Therefore, this would require subjects to be reconsented and made aware 
of any reported events. 
 
13.1.16 Reporting of Pregnancy 
If a female subject becomes pregnant during the 8-week period post-FMT, the physician must be 
notified as soon as possible and will document it in the subject’s research binder or medical chart. 
The subject subsequently will cease further study procedures (week 8 flexible sigmoidoscopy) and 
blinded FMT intervention and will only continue to complete the safety follow-ups. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
42 
 
13.2 Definition of SAE 
 
Serious adverse events (SAEs) are any adverse experience occurring during or after FMT that results 
in any of the following outcomes: death, life threatening adverse experiences, hospitalization or 
prolongation of hospitalization, disability or incapacitation, overdose, congenital anomalies and any 
other serious events that may jeopardize the subject or require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.  
 
13.2.1 Reporting of SAE to IRB 
 
All SAEs occurring on this study will be reported to the IRB according to the IRB policy, which can 
be accessed via the following link:   
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting_Poli
cy.pdf.  
 
13.2.2 Reporting of SAE to FDA [For Protocols Where WCMC is the Sponsor-Investigator] 
 
IND application sponsor-investigators must report any suspected adverse reaction or adverse 
reaction to study treatment that is both serious and unexpected. Unexpected fatal or life-
threatening suspected adverse reactions represent especially important safety information and 
must be reported expeditiously by the treating physician to the FDA in a written IND safety report 
within 7 calendar days following the initial receipt of the information. Examples of SAE may be 
any of the following: 
i. death, 
ii. a life-threatening adverse event, 
Note: An adverse event or suspected adverse reaction is considered life-threatening if, in the view 
of the investigator or sponsor, its occurrence places the patient or subject at immediate risk of 
death. It does not include an adverse event or suspected adverse reaction that, had it occurred in 
a more severe form, might have caused death. 
iii. in-patient hospitalization or prolongation of existing hospitalization 
Note: Adverse events requiring hospital admissions that are less than 24 hours in duration do not 
meet this criterion. A scheduled hospitalization for a pre-existing condition that has not worsened 
during participation in the study does not meet this criterion. Pre-planned hospitalizations for an 
elective medical/surgical procedure or routine check-ups do not meet this criterion. 
iv. a persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or   
v. a congenital anomaly or birth defect. 
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or research subject and may require medical or surgical intervention 
to prevent one of the outcomes listed as serious 
 
Any observation that is also an AE will be recorded in the medical record along with any actions 
taken. If not, all information will be available at the time of initial report and follow-up SAE reports 
will be completed and submitted. Anticipated and less serious adverse events will be submitted 
annually in reports to the FDA. 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
43 
 
CDER INDs:  
Food and Drug Administration  
Center for Drug Evaluation and Research  
Therapeutic Biological Products Document Room 5901-B  
Ammendale Road Beltsville, MD 20705-1266 
 
13.2.3 Reporting of SAE to OpenBiome 
 
OpenBiome requests any and all adverse event reports to be submitted through their online form: 
www.openbiome.org/adverse-events at the time of the annual FDA and IRB continuing 
review submissions. Once the form is submitted, a triage call may be set up with the report’s 
author and a Finch medical professional to assess cases according to FDA ruling. Then, 
Finch/OpenBiome clinical staff may work with WCM clinical/research staff to determine the next 
steps in the investigation, which may or may not include reporting a Form FDA 3500. The Clinical 
Safety team at OpenBiome can also be directly reached at safety@openbiome.org or by phone at 
(617) 575-2201, option 9. 
 
13.2.4 Protocol-Specific Exceptions to SAE Reporting 
 
A suspected clinical endpoint event, regardless of when the event occurs, is not to be reported as 
an AE or SAE or reported in an expedited manner as an SAE. The suspected clinical endpoint event 
includes: 
• 
Recurrent UC flare 
• 
Initial response to therapy with initial reduction to Mayo score ≤3 with an accompanying 
decrease in the sub-score for rectal bleeding of at least 1 point or an absolute sub-score 
for rectal bleeding of 0 or 1 
 
13.3 AE/SAE Follow Up 
 
All SAEs and AEs reported during this study require the investigator to follow them until resolution or 
until the investigator confirms that the AE/SAE has stabilized and no more follow-up is required. This 
requirement indicates that follow-up may be required for some events after the subject discontinues 
participation from the study. Resolution is defined as: 
a. Resolved with or without residual effects 
b. Return to baseline for a pre-existing condition 
c. Fatal outcome; if autopsy is performed, the autopsy report must be provided to the 
sponsor. 
13.4 Time Period and Frequency for Event Assessment  
 
13.4.1. AE/SAE Monitoring 
 
Each enrolled subject will be monitored for the occurrence of AEs, including SAEs, beginning 
immediately after FMT. The occurrence of an adverse event (AE) or serious adverse event (SAE) 
may come to the attention of study personnel during study visits and interviews of a study 
participant presenting for medical care, or upon review by a study monitor. Subjects will be 
questioned at each follow up time-point about unsolicited and solicited AE on stool form and 
frequency, presence of abdominal pain, fevers and subjective well-being and/or examined (at day 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
44 
 
1, 2, 6, 10 and 12 weeks post-FMT via phone call; 4 and 8 weeks post-FMT via office visit and 
review of patient diary for AE monitoring) by the treating physician for evidence of AEs. The 
questioning of subjects with regard to unsolicited adverse events will be generalized such as, 
"How have you been feeling since your last visit?”. The following AEs will be solicited via phone 
calls and clinic visits by a study coordinator, along with the intensity of each: 
1. Fever 
a. Mild: Temperature 37.7-38.6°C 
b. Moderate: Temperature 38.7-39.3°C 
c. Severe: Temperature 39.4-40.5°C 
d. Potentially Life Threatening: Temperature >40.5°C 
2. Chills 
a. Mild: No or minimal interference with usual social and functional activities 
b. Moderate: Greater than minimal interference with usual social and functional 
activities 
c. Severe: Inability to perform usual social and functional activities 
3. Fatigue/Malaise 
a. Mild: No or minimal interference with usual social and functional activities 
b. Moderate: Greater than minimal interference with usual social and functional 
activities 
c. Severe: Inability to perform usual social and functional activities 
d. Potentially Life Threatening: Incapacitating fatigue or malaise symptoms 
causing inability to perfume basic self-care functions. 
4. Anorexia (loss of appetite)  
a. Mild: Loss of appetite without decreased oral intake 
b. Moderate: Loss of appetite with decreased oral intake without significant 
weight loss 
c. Severe: Loss of appetite with decreased oral intake associated with significant 
weight loss 
d. Potentially Life Threatening: Life threatening consequences or aggressive 
intervention indicated (TPN or tube feeding) 
5. Abdominal Pain 
a. Mild: Pain causing no or minimal interference with usual social and functional 
activities.  
b. Moderate: Pain causing greater than minimal interference with usual social 
and functional activities.  
c. Severe: Pain causing no inability to perform usual social and functional 
activities.  
d. Potentially Life Threatening: Disabling pain causing inability to perform basic 
self-care functions or hospitalization (other than an emergency room visit) 
indicated. 
6. Constipation 
a. Mild: Irregularity of bowel movements not requiring dietary modification, 
laxative or enema. 
b. Moderate: Persistent constipation requiring regular use of dietary 
modifications, laxatives or enemas.  
c. Severe: Obstipation with manual evacuation indicated 
d. Potentially Life Threatening: Life threatening consequences (i.e. obstruction) 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
45 
 
7. Diarrhea 
a. Mild: Transient or intermittent episodes of unformed stools or increase of ≤3 
stools over baseline per 24-hour period 
b. Moderate: Persistent episodes of unformed to watery stools or increase of 4-
6 stools over baseline per 24-hour period 
c. Severe: Bloody diarrhea OR increase of ≥7 stools per 24-hour period or IV 
fluid replacement indicated 
d. Potentially Life Threatening: Life threatening consequences (i.e. hypotensive 
shock) 
8. Nausea 
a. Mild: Transient (<24 hours) or intermittent nausea with no or minimal 
interference with oral intake.  
b. Moderate: Persistent nausea resulting in decreased oral intake for 24-48 
hours 
c. Severe: Persistent nausea resulting in minimal oral intake for >48 hours or 
aggressive rehydration indicated (IV fluids).  
d. Potentially Life Threatening: Life threatening consequences (i.e. hypotensive 
shock) 
9. Vomiting 
a. Mild: Transient or intermittent vomiting with no or minimal interference with 
oral intake.  
b. Moderate: Frequent episodes of vomiting with no or mild dehydration. 
c. Severe: Persistent vomiting resulting in orthostatic hypotension or aggressive 
rehydration indicated (IV fluids).  
d. Potentially Life Threatening: Life threatening consequences (i.e. hypotensive 
shock) 
Study coordinators will report any and all AE/SAE to the treating clinician and/or PI and they will 
contact the subject for follow-up. Additionally, Subjects will also be instructed to contact the 
treating physician at any time point post-FMT to report symptoms experienced. 
• 
Patients having AEs will be monitored with relevant clinical assessments and laboratory 
tests, as determined by the treating physician. 
• 
AEs, actions taken as a result of AEs, and follow-up results must be recorded in the 
patient’s medical record.    
• 
In addition, patients will receive a follow up phone call 6-months post FMT and every 
subsequent 6 months for the next year to record any SAEs, new medical conditions and 
diagnoses, or changes in conditions or diagnoses since last study contact.   
For all SAEs and AEs, relevant clinical assessments and laboratory tests will be repeated as 
clinically appropriate, until final resolution or stabilization of the event(s). 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on 
the appropriate electronic case report form (eCRF). Information to be collected includes event 
description, time of onset, clinician’s assessment of severity, relationship to study product 
(assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
46 
 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of 
the event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
 
Study coordinators will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day 
of study participation.  At each study visit, the investigator will inquire about the occurrence of 
AE/SAEs since the last visit.  Events will be followed for outcome information until resolution or 
stabilization. 
 
13.4.2. AE/SAE Assessment 
 
13.4.2.1 Assessment of Severity 
 
The severity of AEs will be assessed according to the following definitions: 
• 
Mild: The AE is noticeable to the patient and/or the Investigator but does not 
interfere with routine activity. 
• 
Moderate: The AE interferes with routine activity but responds to symptomatic 
therapy or rest. 
• 
Severe: The AE significantly limits the patient’s ability to perform routine activities 
despite symptomatic therapy. 
• 
Life-threatening/disabling: The AE puts patient as risk of death. This does not 
refer to an event that may hypothetically have caused death if it were more 
severe. 
 
13.4.2.2 Assessment of Causality 
 
The physician must assess the relationship of any AE (including SAEs) to FMT, as related 
or not related, based on clinical judgment and using all available information, and may 
include consideration of the following factors: 
a. Possible alternative causes of the AE, including the disease under treatment, pre-
existing conditions, concomitant use of other drugs, and presence of 
environmental or genetic factors. 
b. The temporal association between FMT exposure and onset of the AE. 
c. Whether the manifestations of the AE are consistent with known actions or 
theoretical toxicity of FMT. 
 
The causal relationship between FMT and the AE will be assessed using one of the 
following categories: 
a. Not Related: An AE is not associated with FMT if: 
o An event that can be determined with certainty to have no relationship to the 
FMT. 
o Temporal relationship is lacking (i.e. the event did not occur within a 
reasonable time frame following administration of FMT) 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
47 
 
o Other causative factors more likely explain the event (i.e. pre-existing 
condition, other concomitant treatments);  
b. Definitely Related:  
o There is a positive temporal relationship (i.e. the event occurred within a 
reasonable time frame following FMT) 
o The AE is more likely explained by FMT than by another cause 
o Previously known toxicity of FMT. 
c. Probably Related: 
o  There is a positive temporal relationship (i.e. the event occurred within a 
reasonable time frame following FMT) 
o The AE is more likely explained by FMT than by another cause 
o Unlikely to be explained by patient’s clinical state or other intervention. 
d. Possibly Related: 
o There is a positive temporal relationship (i.e. the event occurred within a 
reasonable time frame following FMT) 
o Event follows an expected response pattern to FMT, but event could have 
occurred secondary to a number of other factors. 
 
14. Unanticipated Problems Involving Risks to Subjects or Others 
 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSO) 
 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks 
to participants or others to include, in general, any incident, experience, or outcome that meets all of 
the following criteria: 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that 
are described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of 
the participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused by 
the procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
48 
 
 
 
14.1.2 Unanticipated Problem Reporting 
 
The sub-investigators will report unanticipated problems (UPIRTSOs) to the reviewing 
Institutional Review Board (IRB) and to the lead principal investigator (PI). The UPIRTSO report 
will include the following information: 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB 
project number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UPIRTSO;  
• 
A description of any changes to the protocol or other corrective actions that have been 
taken or are proposed in response to the UPIRTSO. 
 
To satisfy the requirement for prompt reporting, UPIRTSOs will be reported using the following 
timeline:   
• 
UPIRTSOs that are serious adverse events (SAEs) will be reported to the IRB within 1 week 
of the investigator becoming aware of the event.  
• 
Any other UPIRTSO will be reported to the IRB within 2 weeks of the investigator 
becoming aware of the problem.  
• 
All UPs should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the supporting agency head (or designee), 
Food and Drug Administration (FDA), and the Office for Human Research Protections 
(OHRP) within one month of the IRB’s receipt of the report of the problem from the 
investigator. 
 
15. Data and Safety Monitoring Plan (DSMP) 
 
A Weill Cornell Medicine Data Safety Monitoring Board (WCM DSMB) will monitor the data collected in 
this clinical trial on a quarterly basis to ensure the safety of enrolled subjects. The first periodic report to 
the DSMB will be within 3 months after enrolling the first subject and will be submitted through the 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
49 
 
following 
link: 
https://research.weill.cornell.edu/integrity-compliance/research-support/human-
research/data-safety-monitoringboard/make-submission. This monitoring plan was chosen for this 
clinical trial because it will be randomized and is intended to provide definitive information on the 
effectiveness and safety of FMTs and fiber supplements in active UC patients. 
 
We will minimize the risk of UC relapse/flare by maintaining close clinical contact with all enrolled 
subjects.  They will be encouraged to contact the clinical team if they experience recurrence of diarrhea, 
fever or abdominal pain so that further work up can be initiated, and escalation of standard therapy as 
appropriate. Solicited and unsolicited AEs will be recorded at day 1, week 2, week 6, week 10, week 12, 6 
months, and every subsequent 6 months for 1-year post-FMT via phone calls and at 4 weeks, 8 weeks, 
and 12 weeks via clinic visit by any study team member. They will record any SAEs, new medical 
conditions/diagnoses or changes in medical conditions/medications since last study contact. If any events 
are noted during these follow-up evaluations, they will promptly be reported and reviewed by the treating 
physician and/or lead PI.  
 
15.1. Plan for informed consent compliance  
 
Written, informed consent will be obtained from each subject prior to the performance of any study 
procedures or assessments. Prior to enrolling a subject into the study, a designated member of the 
study team will explain the study protocol as outlined in the informed consent, procedures and 
objectives to the subject and/or authorized representative. When the subject, or legally authorized 
representative agrees to participation in the clinical trial, he/she or authorized representative must 
understand, sign and date the IRB approved Informed Consent Document which describes the study 
and potential discomforts, risks and benefits of participating. One copy of the consent form will be 
provided to the subject and one copy will be maintained with the subject's permanent medical 
records. 
 
15.2. Plan for HIPAA compliance 
 
We will minimize potential risks due to loss of confidentiality by having all information collected and 
handled by research staff trained to deal appropriately with sensitive clinical issues. Computer data 
files will be available only to authorized personnel and no names or obvious identifying information 
will be stored in data files. No participant will be identified in any report to the FDA. Further, when 
contacting participants for follow-up, no identifying information other than the first name of the caller 
will be used when leaving messages or speaking to anyone other than the patient him/herself. Written 
consent will be obtained to contact other persons for the purpose of locating the participant for 
follow-up and participants can refuse or revoke such consents. No information about participants will 
be released without their permission or where required by law. 
 
15.3. Annual Reporting  
 
The safety of patients will be monitored during each contact with patients. Both anticipated and 
unanticipated adverse events and problems will be formally monitored and recorded. Unanticipated 
serious adverse events or problems will be reported to the hospital and university IRBs (as per local 
reporting requirements), the FDA (within 15 days; or 7 days for unexpected fatal or life-threatening 
events or transmission of infectious agent). Anticipated and less serious adverse events will be 
submitted annually in reports to the FDA.  
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
50 
 
The sponsor will provide the following for the annual report under 21 CFR 312.33(b);  
1. Percentage of patients with at least one AE (within pre-specified time periods) 
2. Percentage of patients with at least one SAE (within pre-specified time periods) 
3. Percentage of patients who did/did not experience relapse in the 12 weeks post-FMT 
 
15.4. Halting Rules  
 
The DSMB will have the power to halt the treatment of patients under this protocol if it is determined 
that safety concerns exist. Any safety issues will be discussed with the research team and all 
reportable AEs will be communicated to the FDA as detailed above in IND amendment 1 Section 9 and 
12. Specifically if the IND is halted for review, the FDA will be notified within 2 business days. Specific 
safety findings will result in temporarily suspending enrollment until a safety review is convened, the 
objective of which is a decision as to whether the study should continue per protocol, proceed with 
caution, be further investigated, be discontinued, or be modified and then proceed. Suspension of 
enrollment (for a particular group or for the entire study) is another potential outcome of a safety 
review. 
 
Subsequent review of serious, unexpected, and related AEs by the DSMB, IRB, the sponsor, or the FDA 
or relevant local regulatory authorities may also result in suspension of further trial 
interventions/administration of FMT at our site. The FDA and study sponsor(s) retain the authority to 
suspend additional enrollment and study interventions/administration of FMT for the entire study, as 
applicable. Findings that will trigger a safety review are: 
• 
Death 
• 
Transmission of an infection from donor to subject via FMT 
• 
If more than 10% of subjects experience the same Grade 3 Adverse Event 
• 
If one or more subjects experiences a serious, unexpected adverse event 
• 
Increased frequency of events (specifically, new diagnoses of inflammatory bowel disease in 
> 2 FMT treated subjects). 
FDA will be notified by phone, email, or fax within 48 hours if the study is halted for review. 
 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
51 
 
References 
 
1. Marie E. Robert, Mark Skacel, Thomas Ullman, Charles N. Bernstein, Kirk Easley, John R. 
Goldblum. Patterns of Colonic Involvement at Initial Presentation in Ulcerative Colitis Am J Clin 
Pathol 2004; 122:94-99 
2. Siew C Ng, Hai Yun Shi, et al. The Lancet 2017 390, 2769-2778DOI: (10.1016/S0140-
6736(17)32448-0)  
3. Loftus EV Jr Update on the Incidence and Prevalence of Inflammatory Bowel Disease in the 
United States. Gastroenterol Hepatol. 2016 Nov;12(11):704-707. 
4. Imuran (azathioprine). In: Prometheus Laboratories I, ed. accessdata.fda.gov. San Diego, 
California.May 2011. 
5. Purinethol (mercaptopurine). In: DSM Pharmaceuticals I, ed. accessdata.fda.gov. Greenville, 
North Carolina.April 2011. 
6. Mao EJ, Hazlewood GS, Kaplan GG, Peyrin-Biroulet L, Ananthakrishnan AN. Systematic review 
with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing 
hospitalisation and surgery in Crohn's disease and ulcerative colitis. Aliment Pharmacol 
Ther. 2017 Jan;45(1):3-13. doi: 10.1111/apt.13847. 
7. Remicade (infliximab). In: Janssen Biotech I, ed. accessdata.fda.gov. Horsham, 
Pennsylvania 2013. 
8. Cimzia (certolizumab pegol). In: UCB I, ed. accessdata.fda.gov. Smyrna, Georgia.September 
2013. 
9. Humira (adalimumab). In: AbbVie I, ed. accessdata.fda.gov. North Chicago, Illinois.January 2013. 
10. Asher Kornbluth, MD1, David B. Sachar, MD, MACG1 and The Practice Parameters Committee of 
the American College of Gastroenterology. Ulcerative Colitis in Adults Am J Gastroenterol 2010; 
105:501–523 
11. Jostins L, Ripke S, Weersma RK, et al. (2012). Host-microbe interactions have shaped the genetic 
architecture of inflammatory bowel disease. Nature.http://doi.org/10.1038/nature11582  
12. Gut microbiota in the pathogenesis of inflammatory bowel disease. Atsushi Nishida, Ryo Inoue, 
Osamu Inatomi, Shigeki Bamba, Yuji Naito, Akira Andoh Clinical Journal of Gastroenterology 
2018, 11 (1): 1-10 
13. Jeon SR, Chai J, Kim C, Lee CH Current Evidence for the Management of Inflammatory Bowel 
Diseases Using Fecal Microbiota Transplantation. Current Infectious Disease Reports 2018 May 
26, 20 (8): 21 
14. van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent 
Clostridium difficile. N Engl J Med. Jan 2013;368(5):407-415. 
15. Noortje G. Rossen, Susana Fuentes, Mirjam J. van der Spek, Jan G. Tijssen, Jorn H. A. Hartman, 
Ann Duflou, Mark Löwenberg, Gijs R. van den Brink, Elisabeth M. H. Mathus-Vliegen, Willem M. 
de Vos, Erwin G. Zoetendal, Geert R. D’Haens, and Cyriel Y. Ponsioen. Findings From a 
Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis 
Gastroenterology 2015;149:110–118 
16. Paul Moayyedi, Michael G. Surette, Peter T. Kim, Josie Libertucci, Melanie Wolfe, Catherine 
Onischi, David Armstrong, John K. Marshall, Zain Kassam, Walter Reinisch, and Christine H. Lee. 
Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in 
a Randomized Controlled Trial Gastroenterology 2015;149:102–109 
17. Paramsothy S, Paramsothy R, Rubin DT, Kamm MA, Kaakoush NO, Mitchell HM, Castaño-
Rodríguez N. Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic 
Review and Meta-analysis. J Crohns Colitis. 2017 Oct 1;11(10):1180-1199 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
52 
 
18. Vinita Jacob, Carl Crawford, Shirley Cohen-Mekelburg, Monica Viladomiu, Gregory G. Putzel, 
Yecheskel Schneider, Fatiha Chabouni, Sarah O'Neil, Brian Bosworth, Viola Woo, Nadim J. Ajami, 
Joseph F. Petrosino, Ylaine Gerardin, Zain Kassam, Mark Smith, Iliyan D. Iliev, Gregory F. 
Sonnenberg, David Artis, Ellen Scherl, Randy S. Longman; Single Delivery of High-Diversity Fecal 
Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in 
Active Ulcerative Colitis, Inflammatory Bowel Diseases, Volume 23, Issue 6, 1 June 2017, Pages 
903–911  
19. João P.B. Silva, Kely C. Navegantes-Lima, Ana L.B. Oliveira, Dávila V.S. Rodrigues, Sílvia L.F. 
Gaspar, Valter V.S. Monteiro, Davi P. Moura and Marta C. Monteiro*, “Protective Mechanisms 
of Butyrate on Inflammatory Bowel Disease”, Current Pharmaceutical Design (2018) 24: 4154 
20. Bach Knudsen, K.E.; Lærke, H.N.; Hedemann, M.S.; Nielsen, T.S.; Ingerslev, A.K.; Gundelund 
Nielsen, D.S.; Theil, P.K.; Purup, S.; Hald, S.; Schioldan, A.G.; Marco, M.L.; Gregersen, S.; 
Hermansen, K. Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and 
Inflammation. Nutrients 2018, 10, 1499. 
21. Arpaia N, Campbell C, Fan X et al. Metabolites produced by commensal bacteria promote 
peripheral regulatory T-cell generation. Nature 2013; 504: 451–455.  
22. Furusawa Y, Obata Y, Fukuda S et al. Commensal microbe-derived butyrate induces the 
differentiation of colonic regulatory T cells. Nature 2013; 504: 446–450.  
23. S.R. Llewellyn, G.J. Britton, E.J. Contijoch, O.H. Vennaro, A. Mortha, J.F. Colombel, A. Grinspan, 
J.C. Clemente, M. Merad, J.J. Faith. Interactions between diet and the intestinal microbiota alter 
intestinal permeability and colitis severity in mice. Gastroenterology. 2017 Nov 23. pii: S0016-
5085(17)36388-6. doi: 10.1053/j.gastro.2017.11.030 
24. Ana Letícia Malheiros Silveira, Adaliene Versiani Matos Ferreira, et al. Preventive rather than 
therapeutic treatment with high fiber diet attenuates clinical and inflammatory markers of acute 
and chronic DSS-induced colitis in mice European Journal of Nutrition 2017, 56 (1): 179-191 
25. Sonnenburg E.D., Zheng H., Joglekar P., et al: Specificity of polysaccharide use in intestinal 
bacteroides species determines diet-induced microbiota alterations. Cell 2010; 141: pp. 1241-
1252 
26. K. Khan, E. Jovanovski, H.V.T. Ho, A.C.R.Marques, A. Zurbau, S.B. Mejia, J.L.Sievenpiper, V. Vuksa
n. The effect of viscous soluble fiber on blood pressure: A systematic review and meta-analysis 
of randomized controlled trials. Nutrition, Metabolism and Cardiovascular Diseases, Volume 28, 
Issue 1, 2018, pp. 3-13 
27. Linda Wedlake, Natalie Slack, H. Jervoise N. Andreyev, Kevin Whelan; Fiber in the Treatment and 
Maintenance of Inflammatory Bowel Disease: A Systematic Review of Randomized Controlled 
Trials, Inflammatory Bowel Diseases, Volume 20, Issue 3, 1 March 2014, Pages 576-
586, https://doi.org/10.1097/01.MIB.0000437984.92565.31 
28. Llewellyn SR, Britton GJ, Contijoch EJ, Vennaro OH, Mortha A, Colombel JF, Grinspan A, Clemente 
JC, Merad M, and Faith JJ. Interactions Between Diet and the Intestinal Microbiota Alter Intestinal 
Permeability and Colitis Severity in Mice. Gastroenterology. 2018;154(4):1037-46 e2. 
29. Chen L, He Z, Iuga AC, Martins Filho SN, Faith JJ, Clemente JC, Deshpande M, Jayaprakash A, 
Colombel JF, Lafaille JJ, et al. Diet Modifies Colonic Microbiota and CD4(+) T-Cell Repertoire to 
Induce Flares of Colitis in Mice With Myeloid-Cell Expression of Interleukin 23. Gastroenterology. 
2018;155(4):1177-91 e16. 
30. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy 
for ulcerative colitis. N Engl J Med. Dec 2005;353(23):2462-2476. 
31. Rosner B. Fundamentals of Biostatistics. 7th ed. Boston, MA: Brooks/Cole; 2011. 


IRB Protocol #: 19-04020045 
Version Date: 11/13/2024 
  
53 
 
32. Wong, C., Harris, P. J., & Ferguson, L. R. (2016). Potential Benefits of Dietary Fibre Intervention in 
Inflammatory Bowel Disease. International journal of molecular sciences, 17(6), 919. 
doi:10.3390/ijms17060919 
33. U.S. Food and Drug Administration (FDA, 2016). "Memorandum to the File: Scientific Review of 
the Beneficial Physiological Effects of Non-Digestible Carbohydrates for Meeting the FDA 
Definition of Dietary Fiber," 2016.  
34. P, Editor(s): Ronald I. Shorr, Angela B. Hoth, Nathan Rawls, Drugs for the Geriatric Patient, W.B. 
Saunders, 2007, Pages 930-1062. ISBN 9781416002086. https://doi.org/10.1016/B978-
141600208-6.50019-X.