The Use of Fecal Microbiota Transplantation in Patients With Ulcerative Colitis-associated Pouchitis
Phase: PHASE2
Conditions: Ulcerative Colitis Associated Pouchitis
Sponsor: Virginia O. Shaffer

 
 
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Protocol and Statistical Analysis Plan 
 
IRB00071015 
NCT02049502 
 
Title: The Use of Fecal Microbiota Transplantation in Patients  
with Ulcerative Colitis-associated Pouchitis 
 
Principal Investigator: Virginia Shaffer, MD, Associate  
Professor of Surgery, Emory University School of Medicine 
 
Date 06/26/2017 

 
 
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Title: The Use of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis-
associated Pouchitis 
 
Principal Investigator: Virginia Shaffer, MD, Associate Professor of Surgery, Emory 
University School of Medicine 
 
Emory University School of Medicine 
Divisions of Digestive Diseases and Infectious Diseases,  
Department of Surgery 
 
 Research Protocol 
 
Title: The Use of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis-
associated Pouchitis 
 
Principal Investigator: Virginia Shaffer, MD, Associate Professor of Surgery, Emory 
University School of Medicine 
 
 
1. SPECIFIC AIMS 
 
The aims of this study are: 1) to determine the utility of fecal microbiota transplantation 
(FMT) in the treatment of patients with ulcerative colitis (UC) associated chronic antibiotic-
dependent pouchitis (CADP) and chronic antibiotic refractory pouchitis (CARP) and 2) to 
study the changes in the microbial environment in patients with pouchitis (pre- and post-
treatment) and 3) to assess the impact of therapy on the patient's perceived quality of life. 
 
2. BACKGROUND AND RATIONALE 
 
The spectrum of inflammatory bowel diseases (lBO) includes ulcerative colitis (UC) and 
Crohn's disease (CD).  The etiology of these diseases is not clear but appears to involve 
aberrant immunological responses to intestinal bacteria in a genetically predisposed host.  
There is increasing evidence that the intestinal microbiota play an important role in the 
initiation and maintenance of lBO.  Studies have demonstrated that the microbiota in patients 
with lBO differ from the healthy non-IBD individuals with a decrease in species such as 
Clostridium leptum and Faecalibacterium prausnitzii.   This "dysbiosis" may result in fewer 
bacteria that produce short chain fatty acids which are important in protecting intestinal 
epithelium.  The intestinal microbiota is important in maintaining homeostasis in the intestine 
and interacts with the host immune system to enhance immune function.  Manipulation of 
the gut bacteria through the use of antibiotics, probiotics, and prebiotics have been shown 
to be beneficial in lBO.   The use of antibiotics for the treatment of mild to moderate active 

 
 
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colonic Crohn's disease is effective in many cases.  Antibiotics are often used to treat acute 
episodes of UC-associated pouchitis, an inflammatory condition seen in patients who undergo 
a restorative proctocolectomy with an ileal pouch anastomosis (IPAA).  Probiotics (such as 
VSL-3) for the treatment of acute UC-associated pouchitis as well as for the secondary 
prevention of repeated episodes of pouchitis have been evaluated in several studies with 
positive results. 
 
Greater than 50% of lBO patients who undergo an IPAA will develop pouchitis.  Many of these 
patients will develop recurrent episodes of pouchitis and up to 5% will develop chronic pouchitis 
requiring maintenance therapy with antibiotics or other agents and may even pouch excision. 
The etiology of pouchitis is unknown, but theories include fecal stasis leading to bacterial 
overgrowth and alteration of normal commensal flora in a genetically susceptible individual.  
Microbiome studies in UC pouch patients have shown alterations in the fecal flora with increases 
in anaerobic bacteria and sulfate producing bacteria. 
 
In a recent study, pouch microbiomal environments appeared to be distinctly unique in patients 
with a normal UC-associated IPAA and those with UC-associated pouchitis (Zelia GC, IBD, 
May 2011).  Pouchitis samples showed more Clostridium and Eubacterium genera compared to 
healthy UC pouch patients.  The current treatment approaches for pouchitis are based on small 
randomized controlled trials showing some efficacy with use of antibiotics and probiotics.  
However, the choice of antibiotics, dose, and duration of treatment are largely empiric.  In 
addition, probiotics have limited durability after discontinuation, while the antibiotics most 
utilized have known side effects as well as the potential for selecting multi-drug resistant 
bacteria. Development and study of additional therapeutic options for pouchitis treatment are 
areas for further research. 
 
Fecal microbiota transplantation (FMT) has been shown safe and effective as a method of 
manipulating the microbiota in patients with recurrent Clostridium difficile infection (van Nood 
et al. NEJM 2013). In the literature, there are 41 cases in 17 articles reported of fecal 
transplantation in the treatment of inflammatory bowel disease (IBD). The majority experienced 
a reduction of symptoms (19/25), cessation of IBD medications (13117), or disease remission 
(15/24) (Anderson, Edney et al. APT 2012). Some ofthe weaknesses ofthe available data are 
small number of cases, unreported or not clearly defined IBD characteristics, and lack of 
uniformity when measuring outcome variables.  A recent prospective controlled pilot trial of 
use of FMT for chronic refractory pouchitis revealed negative outcomes.  However, the 
researchers used a single dose and administered the stool preparation through a nasogastric tube.  
Several studies have shown lower success rates of FMT in C. difficile with use of nasofeeding 
tube versus a colonoscopy or sigmoidoscopy.  In addition, a recent trial of use of FMT to treat 
ulcerative colitis showed improvement in clinical activity scores when five successive fecal 
enemas were used (Kunde 20 13). At the present, it is unclear which phenotype of IBD-ulcerative 
colitis, Crohn's disease, or pouchitis or what level of disease activity is best treated with fecal 

 
 
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microbiota transplantation. 
 
In collaboration with sub-Investigator Colleen Kraft, MD, sixty-two (62) fecal microbiota 
transplants have been attempted in 56 patients at our institution for the indication of refractory 
C. difficile infection. One patient who consented for the study was found to have graft-versus- 
host disease was not transplanted. 
 
To date, 61 FMT procedures have been completed in 55 patients. Data is available on 48 FMTs 
performed on 42 patients. 
 
Eight FMTs have experienced relapse: 
- l patient relapsed due to abx for UTI - resolved after receiving course of vancomycin 
- 2 solid organ transplant patients with FMTs relapsed but improved after 
receiving a second infusion 
- 1 patient required total of 3 FMTs (1 via Dobhoff, 2 colon) 
- 1 patient required total of 2 FMTs via colon 
- 1 patient was 95 y/o NH patient 
- 1 patient had no response to 2 FMT 
 
Three FMT subjects have experienced adverse events: 
- 1 hospital admission due to abdominal pain post FMT in a patient with 
history of irritable bowel. Negative work-up 
- 1 inpatient FMT with abdominal pain post FMT -- negative findings 
- 1 subject experienced episode of diverticulitis post colon FMT1 
 
Additional findings: 
- 2 subjects with diagnosis of collagenous colitis 
- 1 colon cancer 
 
To date, based on available data, there has been a 95% overall response rate (primary, 
secondary, tertiary response rates inclusive). Secondary and tertiary response are defined as 
response to repeat antibiotic therapy and/or repeat FMT. 
 
We hypothesize that the use of FMT in patients with chronic pouchitis symptoms will restore 
the microbial balance in these patients and help treat pouchitis.  This would circumvent the 
need to use chronic antibiotic therapy and/or potentially salvage the pouch, and serve as a 
more durable form of treatment for this group of patients.  In addition, we hope to show that 
the microbial environment of pouchitis patients will change to a more favorable one (as 
defined by the donor microbiota) as determined via 16S ribosomal RNA gene sequencing of 
the microbiota and metabolomic profiling. 
 

 
 
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3. STUDY DESIGN 
 
The primary investigative design will be a single arm study to determine if FMT has the 
potential to be used in the treatment of chronic pouchitis. 
 
3.1 Study Objectives: 
Primary Objective: To determine the safety and tolerability of fecal microbiota transplant 
(FMT) in treatment of chronic pouchitis 
 
Secondary Objective:  To study the microbial environment of IPAA/UC associated 
pouches in patients presenting with symptoms of pouchitis with and without endoscopy-
visualized pouchitis and to assess the impact of the therapy on the patient's perceived quality 
of life 
 
3.2 Study design Type/Phase:  This is a two center, Phase 1 open label study designed to 
determine the safety, tolerability and use of fecal transplant in patients with pouchitis 
and to study the differences in microbiome in patients before and after treatment with 
FMT. 
 
3.3 Sites Centers of Research:  This study will be conducted in the Emory Clinic- Adult 
Digestive Disease Clinic and Colorectal Surgery Clinic, the Emory Center Endoscopy 
Center, and St. Joseph's Hospital (SJH) in Atlanta, GA.  
 
3.4 Measures to minimize/avoid bias: Eligible subjects will be given options of other 
treatments if they choose not to participate. 
 
3.5 Study duration:  The total duration of the study for each patient will be twelve weeks. 
 
3.6 Study Procedures 
 
The following protocol essentially requires two sets of study procedures. One set of study 
procedures outlines testing requirements for the donor of allogenic human feces (see Table 1. 
Donor Related Study Activities). The other set outlines activities and expectations of the research 
participant who will receive the donated stool specimen (see Table 2. Research Participant Study 
Activities). The donor set of activities will be managed by Colleen Kraft, MD, a sub-investigator 
and Associate Professor of Medicine within the Division of Infectious Diseases. In the past, Dr. 
Kraft has overseen the donor recruitment and screening within previous FMT trials via ordering 
the appropriate antibody screens, fecal sample preparation (e.g. use of saline, etc.) and any other 
necessary tests to ensure that the fecal specimen is non-infectious and safe for insertion into 
research participants. Dr. Kraft still oversees this process and prepares the allogenic human fecal 

 
 
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donation in her lab on site. However, she will not be able to provide these activities listed in Table 
1 for effort.  
 
All activities outlined in Table 1 would be billed to the sponsor to compensate Dr. Kraft for her 
time and effort to support our participants and overall project goals and needs. The donor related 
activities will take place before the research participant is seen for informed consent during the 
screening visit (see Table 2). This is done to ensure that the donor has been screened for infectious 
diseases in a timely manner and that Dr. Kraft has ample time to prepare the allogenic human fecal 
specimen in her lab for the transplant on the enrollment visit. Donors will be screened every four 
weeks which is standard protocol for Dr. Kraft’s lab. More details about the donor screening 
process and requirements are listed in the protocol section 3.6 a) Donor Stool Collection and 
Processing.  
 
Table 1. Donor Related Study Activities 
Donor Activity 
Specific Test Ordered 
Visit 
Blood/Serology Testing 
1. Hepatitis A IgM and IgG 
2. Hepatitis B S Ab/Sag/Core Ab 
3. Hepatitis C Ab 
4. RPR 
5. Human Immunodeficiency Virus 
(HIV) 1 and 2 Antibody 
 
 
 
Donor Screening (every four 
weeks) 
Stool Testing 
1.  Clostridium Difficile PCR 
2.  Salmonella, Shigella, and 
Campylobacter 
3.  Ova and parasites 
4.  H. Pylori antigen 
5. 5.Vancomycin resistant 
Enterococcus (VRE) 
6.  Carbapenemase resistant 
Enterobasteriacae 
Fecal Sample Preparation for 
Donation1 
N/A 
 
1The fecal sample will be prepared for the FMT in Dr. Colleen Kraft’s laboratory on site. Please refer to section 3.6 a 
for more detailed information regarding the donor fecal sample processing activities. 
 
Table 2 outlines a total of five complete research visits for each research participant: screening 
(initial), enrollment (transplant), 2 weeks post-transplant (may be a phone call at the discretion of 
the physician), 4 weeks post-transplant, and 3 months post-transplant. For the initial or screening 
visit, research participants will first complete the informed consent process with a member of the 
research team. Upon completion of the informed consent process, the participant will receive 
phlebotomy to collect blood for plasma chemistries, CBC with differential, and platelet counts.  
 
Urine will also be collected and screened for basic urinalysis. Women of child bearing potential 

 
 
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(WOCBP) will be screened using urine pregnancy kits to test for beta HCG levels. These kits will 
be provided by the sponsor. The results of these kits will be used as the final determination of 
pregnancy for WOCBP. WOCBP who screen positive for beta HCG (i.e. are pregnant) will be 
excluded from the study for the safety of both the mother and her unborn child. Phlebotomy for 
plasma collection, eventual CBC with differential, and platelet count will be performed for each 
research visit. Urine and stool will also be collected for each study visit.  In addition to phlebotomy, 
urine collection, and stool collection, research participants will also receive a physical exam for 
each research visit.  
 
Waist and hip circumference will be measured during the screening visit only. For the second visit 
(i.e. enrollment), the research participant will also receive a physical exam along with a flexible 
sigmoidoscopy. The flex sigmoidoscopy will be performed under moderate sedation using propofol 
per usual anesthesia services. The flexible sigmoidoscopy will be used to gain access to the pouch 
and to take a mucosal tissue pouch biopsy.  
 
Table 2. Research Participant Study Activities 
Visit Procedures 
Screening2 
Enrollment 
2 Week3 
(+/- 3 days) 
4 weeks 
(+/- 7 days) 
3months 
(+/- 14 days) 
Informed Consent 
Process 
 
X 
 
 
 
 
Physical Exam 
X 
X 
X 
X 
X 
Urine pregnancy testing 
for WOCBP 
 
X 
 
 
 
 
Phlebotomy 
X 
X 
X 
X 
X 
Labs and Specimen 
Processing: 
Stool collection 
Plasma collection 
Urine collection 
CBC w/diff., platelet count4 
 
 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
Flexible    
Sigmoidoscopy with 
Moderate Sedation 
 
 
X 
 
 
 
Mucosal Biopsy 
Collection 
 
 
X 
 
 
 
Waist and hip 
circumference measures 
 
X 
 
 
 
 
 
Fecal Microbiota    
Transplant 
 
 
X 
 
 
 

 
 
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Modified PDAI 
X (clinical) 
X 
X (clinical) 
X(clinical) 
X (clinical) 
Quality of Life 
Questionnaires 
X 
X 
X 
Food Recall Questionnaire 
X 
X 
X 
2If both screening and enrollment visits occur within 7 days, research samples may not be recollected at the enrollment 
visit, at the discretion of the investigator 
3The 2-week visit may be conducted over the telephone for subjects who live a significant distance from the 
study site and at the discretion of the study investigator. Biological samples will not be collected on subjects 
who complete visit via telephone, however subject may be asked to mail in a stool sample for testing 
 
4 Screening labs for hemoglobin (Hgb), platelet count, and absolute neutrophil count (ANC) may be performed within 
six months of screening visit 
 
3.6. a) Donor Stool Collection and Processing 
 
The standard donor stool will be obtained from a donor who has undergone testing for potential 
transmittable infections.  These include Hepatitis A, Hepatitis B, Hepatitis C, syphilis, HIV, H 
pylori, Salmonella, Shigella, Campylobacter, C. difficile, as well as screening for ova and 
parasites, and multidrug 
resistant 
organisms 
(specifically 
carbapenemase-producing 
Enterobacteriaceae and vancomycin-resistant Enterococcus). This testing is performed through 
Emory Medical Laboratories.  In addition, the donor will be screened for illnesses that would 
exclude him from donating stool for the current study (see attached screening questionnaire). 
Donor screening will be completed and all results confirmed negative prior to use of donor 
stool for transplant. Standard donors will be re-screened every six months. 
 
The standard donor voids the stool at home just prior to leaving for work in the morning.  The 
stool is dropped off in the microbiology laboratory within 60 minutes of being voided.  The 
stool is processed within 60 minutes of the drop off, and administered within 120 minutes of 
the processing.  The time that elapses from the stool being voided by the donor and administered 
to the patient ranges from 60-240 minutes. Donor stool will be handled as a level 2 biohazard 
with appropriate universal precautions. 
 
Appropriate Personal Protective Equipment (PPE) will be worn by personnel while 
handling/processing donor fecal material: 
• Nitrile gloves will be worn while working with all potentially infectious agents. 
Gloves should be removed before touching common objects in public areas. Hand 
washing will be performed each time gloves are changed. 
• Gloves should be removed prior to removal of other PPE. Gloves should be removed 
before leaving the laboratory. 
• Lab coats will be worn over clothing while handling/processing stool specimen and 
preparing FMT solution 

 
 
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• Contaminated clothing will be decontaminated and laundered on-site or by a 
commercial laundry service. 
• Protective eyewear/goggles will be used, if splash potential exists 
• Laboratory access will be limited to authorized personnel only. 
• Biohazard containers for disposal of contaminated materials are readily accessible in 
the processing area. 
• Good laboratory techniques will be exercised to minimize the formation of aerosols, 
droplets, spatters, splashes. 
 
The FMT processing (performed by Dr. Kraft) involves taking of the standard donor's stool 
which is received in the clinical microbiology laboratory along with a short questionnaire 
(see Appendix 2).  The hood is terminally cleaned with 10% sodium hypochlorite followed 
by 70% ethanol. The hood area is then lined with clean lab mats. Thirty cubic centimeter 
(ccs) saline aliquots are poured into 50 ml centrifuge tubes and 1 cm3 of stool is distributed 
in these aliquot containers. The stool is mixed gently using a tongue depressor until a smooth 
suspension is formed.  The contents are then filtered using a standard Parapak filter. The 
suspension is allowed to settle in the 50-ml centrifuge tube for 10 minutes and then poured 
off into a sterile container.  This filtrate is then drawn up in 60 cc syringes, and labeled "For 
Enteral Use Only". Syringes are placed into sealed biohazard labeled bags for transport. 
 
3.6. b) Fecal Microbiota Transplant (FMT) Procedure 
 
Subjects will be asked to clean out their pouch using two over the counter enemas no longer 
than 3 hours before the procedure time. This is standard of care for patients undergoing routine 
flexible sigmoidoscopy. Subjects will also be asked to take 4 mg of loperamide (over-the-
counter anti-diarrheal medication) one half hour before the FMT. 
 
Subjects will be placed in the left lateral decubitus position with elevated hips in a designated 
private room in clinic or endoscopy suite for 90 minutes of FMT intervention. Subjects will be 
asked to rotate 180 degrees slowly during a 10-minute period.  Subjects will be monitored for 30 
minutes after FMT for any adverse events and discharged. 
 
Concomitant Medications: Permitted concomitant medications:  Patients may remain on 
chronic medications during the study period. 
 
Prohibited medications:  Patients will need to be off antibiotics and probiotics for at 
least 48 hours prior to fecal transplant. 
 
End of the study:  The end of study for each patient is defined as the date of the last visit (i.e. 
3 month visit post-transplant).  
 

 
 
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Timeline: All the proposed aims and enrollments will be carried out within 24-month period. 
We do anticipate a large proportion of eligible subjects may travel to Emory as the interest 
in this therapeutic platform is quite high with us already receiving numerous requests. 
 
3.7 Inclusion and Exclusion criteria 
 
The following lists outline key criteria used by the principal investigator, sub-investigators, and 
study team to determine who can and cannot be in this study.  
 
Inclusion Criteria 
1. Males and females between the ages of 18 and 80 (inclusive) with ulcerative colitis-
associated IPAA with and without pouchitis 
2. Eligible patients will be identified through the Emory Clinic (TEC), St. Joseph’s Hospital 
(SJH), and Emory University Hospital (EUH) 
3. Signed informed consent 
 
Exclusion Criteria 
1. Age <18 years or >80 years of age 
2. Exposure to immunosuppressive   therapy within the 4  weeks prior to enrollment or their 
expected use within 1 month of FMT 
3. Concomitant Clostridium difficile infection 
4. Suspected Crohn' s disease 
5. Documented active infection of any kind 
6. Patients on anti-coagulant therapy, with platelet count less than 50,000, significant 
anemia with hemoglobin< 7, or those with other conditions that place them at increased risk 
of bleeding 
7. Pregnant or breastfeeding women (pregnancy will be verified using urine pregnancy kits)  
8. Need for imminent surgery 
9. Absolute neutrophil count (ANC) < I 000 or history of opportunistic infection 
10. Administration of any investigational drug within one month before FMT 
 
Demographic data, including prior history of pouchitis with sub-classification into chronic 
antibiotic resistant (refractory) pouchitis, chronic antibiotic use as well as previous treatments 
will be recorded. Measures of waist and hip circumference and waist to hip ratio will be 
calculated and recorded. Stool samples, urine, and serum samples will be collected. Patients 
will be screened at entry for enteric pathogens (C. difficile, routine bacterial stool culture, 
ova and parasites) and positive results will exclude entry to the study.  
 
Fecal samples from subjects will be analyzed for microbiome genetics, and metabolomic 
profiles before and four weeks after therapy. Scored symptoms according to the modified 
pouch disease activity index (mPDAI) (Appendix 1) as proposed by Shen et al. will also be 

 
 
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documented before pouch endoscopy. Investigation with biopsy incorporating both 
endoscopic and histologic criteria will be pursued. As per Shen's protocol when developing 
the modified PDAI (mPDAI), biopsies will be taken from the posterior wall of the pouch if 
the pouch has abnormal endoscopic appearance and from areas of maximal inflammation 
(Shen 2003).  In addition to the two to four biopsies that are taken for the pathologist, 
additional biopsies will be taken to study the epithelial microbiome.  
 
No more than 6 total biopsies will be taken. A single gastrointestinal pathologist, blinded to 
the clinical presentations and endoscopic findings, will assess the pouch biopsies for grade of 
inflammation. On the basis of the criteria proposed by Sanborn et al patients with a total PDAI 
of seven or more will be classified as having pouchitis. Symptomatic patients without 
endoscopic and histologic evidence of pouchitis and a PDAI less than seven points will be 
defined as not having pouchitis. All patients undergoing pouchoscopy will receive a universal 
donor fecal transplant deposited in the most proximal limit of the afferent limb after the 
mucosal biopsies are obtained. There will be 2 categories of patients. Patients with pouchitis 
symptoms with endoscopic and histologic evidence of pouchitis, and patients with pouchitis 
symptoms without endoscopic features, but with histologic evidence of pouchitis. 
 
We will assess patient perceived improvement in symptoms and quality of life by asking 
participants to complete two surveys--Short Quality of Life Questionnaire for Inflammatory 
Bowel Disease and the Cleveland Global Quality of Life. Participants will be asked to 
complete these surveys at enrollment and again at 4 weeks and I2 weeks post-FMT procedure 
(Appendix 4). 
 
 
4. BIOLOGICAL SPECIMENS TO BE ACQUIRED 
 
1. Fecal sample- The patient will submit a stool specimen in a container for genomic 
analysis at week 0, week 2, week 4, and week 12.  Prior to enrollment, the patients 
will undergo PCR testing for C. difficile, routine stool culture, and ova and parasites. 
Any remaining stool sample will be used for research purposes for microbiota 
evaluation by 16S sequencing. 
 
2. Mucosal Pouch Tissue -A total of up to 6 mucosal biopsies will be taken during 
routine standard of care flexible sigmoidoscopy procedure in patients undergoing 
investigation for presumed pouchitis or for routine surveillance of the pouch in 
patients without pouchitis.  Two to four will be sent to pathology for assessment of 
histology.  Two to four biopsies will be obtained for research purposes.  No more 
than a total of 6 will be taken. All non-research biopsies will be placed in saline and 
transported to the Pathology Department at Emory immediately. Research related 

 
 
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biopsies will be collected by the study team and transported to the Pathology 
Department at Emory University. 
 
3. Stool- Additional stool will be collected after treatment 4 weeks and 3 months after 
fecal microbial transplant (FMT). If the first and second study visit occur within 
48hours, the second collection of biologic samples will be at the discretion of the 
study doctor. 
 
Samples collected through this study will be given a de-identified code that is not derived from 
or related to information about the individual and is not otherwise capable of being translated 
to identify an individual. The samples will then be barcoded and transported to a central core 
laboratory at Emory University managed by Dr. Colleen Kraft. Fecal and mucosal samples 
will be saved and stored in locked refrigerators/freezers in Dr. Kraft's laboratory in the 
Woodruff Memorial Building. DNA will be extracted for sequencing at this laboratory using 
automated extraction. Sequencing of the 16S regions will be performed in Dr. Kraft's 
laboratory. 
 
Plasma and urine samples will be collected from each patient at study visits as illustrated in 
the study procedures table, and will be barcoded and saved in locked freezers in Dr. Kraft's 
laboratory in the Woodruff Memorial Building until all the samples are collected. At such 
time, they will be transported to Dr. Dean Jones' laboratory in the Whitehead building for 
metabolomic profiling. 
 
Biological samples will not be collected on subjects who complete study visits via telephone 
follow-up. 
 
5. ADDITIONAL DATA COLLECTION 
 
Additional information will also be gathered from the patient's medical chart.  This will 
include demographic information including age, sex and race, as well as clinical information 
such as 
pre-existing medical conditions, allergies, medicines prescribed, diseases that run in the 
patient's family, any previous surgical procedures, and the results of any previous medical 
testing (including biopsy results). 
 
Subjects will be asked to complete a Food Recall Questionnaire at enrollment, week 4 and 
week 12 (Appendix 5). 
 
Any data obtained from the patient's medical record will have any and all identifiable 
information removed and will be kept in a password protected electronic file accessible only 

 
 
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by the authorized study team. 
 
6. REQUIRED NUMBER OF PARTICIPANTS 
 
A total of 11 patients with IPAA/UC related pouchitis will be enrolled over 12 months as 
part of this pilot study. 
 
7. PATIENT SAFETY 
 
The risks of this study are limited to those inherent with mucosal tissue biopsy and fecal 
microbial transplant with use of a flexible sigmoidoscopy. 
 
The primary risk associated with a mucosal tissue biopsy is bleeding from the area of biopsy. 
Significant bleeding from the biopsy site is uncommon, but possible (I in 1,000). Even more 
rarely (I in 3,000), a perforation can be made at the site of biopsy which would require surgery 
to repair. To minimize these risks, standard practice is to not take a biopsy of large vessel, not 
to repair.  
 
To minimize these risks, standard practice is to not take a biopsy of large vessel, not more than 
one biopsy from a given mucosal site and not to over distend the bowel lumen while taking 
biopsies. Furthermore, mucosal biopsies are not painful as the bowel lining does not have pain 
fibers to sense pain. In addition, all the above mentioned risks apply regardless if the biopsy 
is done for donating tissue to this study or for diagnostic purposes. Mucosal biopsy sampling 
will be performed by medical staff with expertise in performing these procedures. 
 
Research associated peripheral blood draws may result in some discomfort or risk of 
bruising at the site of the needle entry. There is a remote risk of fainting from a vasovagal 
response or local infection. These risks will be minimized using trained phlebotomists and 
aseptic technique. Sample collections will be performed with the patient seated or 
recumbent. 
 
There is not significant risk to urine donation. There is not significant risk to stool donation. 
 
The primary risks of fecal microbiota transplantation are transmission of infection and 
potential immune stimulation.  We will be using a standard donor who will be screened for 
transmittable infections through serologic and stool testing.  In addition, the donor will be 
screened clinically for illness in which there is potential for disruption of normal 
gastrointestinal flora such as irritable bowel syndrome.  The donor will be excluded from the 
study if he is found to have such an illness.  The risk associated with placement of the 
transplant enema through flexible sigmoidoscopy is discomfort. Small volume (100 mL-
200mL) enemas will be used to minimize this risk. 

 
 
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7.1 Women of Childbearing Potential (WOCBP) 
 
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive serum 
h u m a n  chorionic gonadotrophin laboratory test (>5 miU/mL) will be excluded from 
participation in this study. 
  
Women of child-bearing potential, defined as all women physiologically capable of becoming 
pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse 
with a male partner and women whose partners have been sterilized by vasectomy or other 
means must agree to use two birth control methods throughout their participation in the 
study. The two methods can be a double barrier method or a barrier method plus a hormonal 
method. 
Subjects will be counseled by the study team regarding adequate forms of contraception. 
 
• Adequate barrier methods of contraception include: diaphragm, condom (by the 
partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal 
contraceptives include any marketed contraceptive agent that includes an estrogen 
and/or a progestational agent. 
• Reliable contraception should be maintained throughout the study. 
Women are considered post-menopausal and not of child bearing potential if they 
have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile (e.g. age appropriate, history of vasomotor symptoms) or six months of 
spontaneous amenorrhea with serum FSH levels > 40 mlU/mL and estradiol < 20 
pg/mL] or have had surgical bilateral oophorectomy (with or without hysterectomy) 
at least six weeks prior to study enrollment. In the case of oophorectomy alone, only 
when the reproductive status of the woman has been confirmed by follow up hormone 
level assessment is she considered not of child bearing potential. 
 
8. ANTICIPATED BENEFITS  
 
Given that over 50% of patients will have a recurrent episode of pouchitis after an initial 
episode. Fecal microbiota transplant has the potential for preventing further episodes and 
obviate the need for repeated course of antibiotics if it proves to be effective. 
  
 
9. DATA ANALYSIS 
 
Patients will be identified by physicians on this protocol in The Emory Clinic or Emory 

 
 
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University Hospital. Patients will be consented using an IRB approved informed consent 
and undergo the procedure on their follow up visit. 
 
Since this is a pilot study, no formal power calculation is provided. Descriptive statistics 
and ANOVA will be used to detect differences between groups. One-sample t-test or 
Wilcoxon's signed rank-tests will be used to see if there were any significant changes in 
PDAI and QOL scores before and after transplant. A Simon's two stage design will be used 
to decide whether to enroll more patients in the future. 
 
Data relating to laboratory results will be obtained through the EMR computerized patient 
information systems EML microbiological reports. A dataset will be created in a secure file, 
with access given only to authorized study staff. 
 
A list of possible cases that have been reviewed for inclusion will be secured by study staff. 
This list will contain subject name, birth date, medical record number, and the number of the 
corresponding data abstraction sheet.  Such a list will be maintained so as not to duplicate 
the abstraction of a single subject.  Once the data from all included subjects is entered into a 
database, the list of identifiable patient information will be destroyed. 
 
Data analysis will be performed with Microsoft Excel, SAS Institute software, and 
SPSS software. 
 
10. 
END POINTS 
 
The primary endpoint of this study will be resolution of clinical pouchitis symptoms using 
the clinical component of the modified pouchitis disease activity index without relapse for 3 
months. Secondary endpoints include 16S ribosomal gene sequencing and metabolomic 
profiles that are more favorable (as defined by the donor microbiota). An additional secondary 
endpoint will be improvement of quality of life as determined by QOL questionnaires. 
 
11. 
DATA SAFETY MONITORING PLAN 
 
A committee consisting of two physicians, Dr Jay Varkey (Assistant Professor, Division of 
Infectious Diseases) and Dr Jenny Han MD, (Assistant Professor, Division of Pulmonary and 
Critical Care) has been created.  Dr. Varkey and Dr. Han have agreed to be part of the 
committee and will not have any direct participation or interests in the study. The committee 
will meet emergently in the event of the reported SAE and consider the future course based 
on the outcome of the event. If no SAE is reported, the committee will meet every 6 months 
to assess the safety and review the AEs. 
 
12.  CLINICAL ADVERSE EVENTS 

 
 
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An adverse event is any untoward medical occurrence in a subject administered the study 
procedure and which does not necessarily have a causal relationship with the study 
procedure. An adverse event can thus be any unfavorable and unintended sign, symptom, 
or disease temporally associated with the use of the study drug, whether or not considered 
related to the study drug. Pre-existing conditions that worsen during the study are 
considered adverse events. For the purposes of this study, AE's related to study procedures 
will be collected. 
 
12.1 Severity 
 
Severity of the adverse event will be defined as follows: 
Mild - Discomfort noticed but no disruption of normal daily 
activity Moderate - Discomfort sufficient to reduce or affect daily 
activity Severe - Inability to work or perform normal daily activity 
Life Threatening - Represents an immediate threat to life. 
 
12.2 Determination of Relationship of Adverse Event to FMT 
 
There will be four categories of possible relationship between the adverse event and FMT. 
Determination of drug-relatedness of the adverse event to FMT will be determined by the 
investigator. 
 
Category 1: Probable (must have first three) 
A probable relationship will be assigned to an adverse event that is considered, with a high 
degree of certainty, to be related to FMT. An adverse event may be considered probable if: 
1. It follows a reasonable temporal sequence from administration of the FMT. 
2. It cannot be reasonable explained by the known characteristics of the subject's clinical 
state, environmental or toxic factors, or other modes of therapy administered to the subject. 
4. It follows a known pattern of response to FMT 
 
Category 2: Possible (must have first two) 
A possible relationship will be assigned to an adverse event when the connection with FMT 
administration appears unlikely but cannot be ruled out with certainty. An adverse event will 
be considered possible if: 
1. It follows a reasonable temporal sequence from administration of FMT 
2. It may have been produced by the subject's clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject 
3. It follows a known pattern of response to FMT 
 
Category 3: Remote (must have first two) 

 
 
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An adverse event will be considered remote if: 
1. It does not follow a reasonable temporal sequence from administration of FMT 
2. It may readily have been produced by the subject's clinical state, environmental or 
toxic factors, or other modes of therapy administered to the subject. 
3. It does not follow a known pattern of response to FMT 
 
Category 4: Unrelated 
An adverse event will be considered unrelated if it is judged to be clearly and   
incontrovertibly due only to extraneous causes such as disease, environment, etc. while not 
meeting the criteria for drug relationship as listed above for remote, possible, or probable. 
 
12.3 Serious Adverse Event 
 
A serious adverse event is any experience that suggests a significant hazard, 
contraindication, side effect or precaution and meets at least one of the following 
criteria: 
• Is fatal (results in death); 
• Is life-threatening; 
• Requires in-patient hospitalization or prolongs existing hospitalization; 
• Results in persistent or significant disability/incapacity; 
• Results in a congenital anomaly/birth defect; 
• Is medically significant or requires intervention to prevent one or other of the 
outcomes listed above. 
 
The clinical judgment of the investigator shall be used in deciding whether a certain situation 
may warrant consideration as a serious adverse event but may not meet the above criteria. 
This medical event may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the subject or may require intervention to prevent one of 
the outcomes listed in the definitions above. 
 
12.4 Reporting of Serious Adverse Events 
 
All adverse events considered serious and unexpected shall be reported to 
• FDA (via form MedWatch 3500-see Appendix 3) within 10 calendar days (by fax) 
• Emory University IRB within 10 business days 
• DSMB within 7 days 
 
13. 
CONFIDENTIALITY 
 
The Investigator will take the following precautionary measures to protect the privacy and 

 
 
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confidentiality of the subject's research and/or medical records. 
• The donated blood and mucosal tissue collected through this study will be given a 
code (or number) that is not derived from or related to information about the 
individual and is not otherwise capable of being translated to identify an individual. 
• Access to medical and research records will be limited to clinical and research 
personnel assigned   to data collection and monitoring for this study.  Only those 
medical records pertaining to the study will be reviewed. 
 
• Research records will be de-identified and maintained in a secured location. 
• Dates recorded on research records will be limited to those essential to completion 
of the study. 
• No individual identifiers will be used in any publications or reports resulting from 
the study. 
 
PI and authorized study staff will have access to a secure file containing linkages of biological 
samples to subject identities. 
A copy of the consent form will be included in the subject's medical research record. 
 
13. 1 Compliance Statement 
 
The study will be conducted in accordance with the protocol, Good Clinical Practices, the 
relevant ICH guidelines, the applicable regulatory requirements, and the ethical principles 
that have their origins in the Declaration of Helsinki. As required by United States Food and 
Drug Administration (FDA) Code of Federal Regulations (CFR) (21 CFR 56) and the 
Declaration of Helsinki, the study protocol, amendments, and Informed Consent form will 
be reviewed and approved, according to 21 CFR §50 and §56, respectively, by IRB. 
 
13. 2 Subject Information and Consent 
 
The study will be explained to each subject, they will have the opportunity to read the 
informed consent document, ask questions and have their questions answered to their 
satisfaction. Alternatives to participation in this study will be explained. Patients will be 
informed that their participation in this study is voluntary and that their decision regarding 
participation will not affect their ability to receive care. Prior to any study procedures, the 
IRB approved Informed Consent form will be signed by each subject.   A copy of the consent 
form will be given to each patient approached for participation in the study. 
 
The Emory University IRB will review the written Informed Consent Form. These 
documents will meet requirements for subject information, as outlined in FDA regulations 
(21 CFR 50), ICH Guideline E6, and the Declaration of Helsinki. 

 
 
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14. 
COSTS 
 
14.1 Donor Activities Related Costs 
 
The cost of all donor serology and stool testing will be covered by the sponsor. Fecal sample 
preparation will also be covered by the sponsor.  
 
14.2. Research Participant Activities Related Costs 
. 
All physical exams will be covered by principal investigator and/or sub-investigator effort. Waist 
to hip circumference will be taken during the physical exam for each visit, therefore, they will also 
be considered as physician effort. Urine pregnancy kits used during for screening WOCBP will be 
covered by sponsor funds. All associated labs and specimen processing (i.e. stool collection, 
plasma collection, urine collection, and CBCs with differential and platelet count will also be 
covered. The flexible sigmoidoscopy with moderate sedation will be covered by the sponsor. 
Eligible research participants who enroll in the study will not be paid for their participation.  
 
15. 
REFERENCES 
 
1. Zelia GC, Hait EJ, Glavan T, Gevers D, Ward DV, Kitts CL, Korzenik JR; Distinct 
microbiome in pouchitis compared to healthy pouches in ulcerative colitis and 
familial adenomatous polyposis. lntlamm Bowel Dis. 2011 May; 17(5):1092-100 
 
2. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser 
CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf, MG, Keller JJ; 
Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl J 
Med.2013 Jan 31;368(5):407-15. 
 
3. Anderson JL, Edney RJ, Whelan K; Systematic review: faecal microbiota 
transplantation in the management of inflammatory bowel disease. Aliment 
Pharmacol Ther. 2012 Sep;36(6):503-16. 
 
4. Kunde S1, Pham A, Bonczyk S, Crumb T, Duba M, Conrad H Jr, Cloney D, 
Kugathasan S.;Safety, tolerability, and clinical response after fecal transplantation  in 
children and young adults with ulcerative colitis.J Pediatr Gastroenterol Nutr. 2013 
Jun;56(6):597-601. doi: 10.1097/MPG.ObO l3e318292fa0d. 
 
5. Shen B, Achkar JP, Connor JT, Ormsby AH, Remzi FH, Bevins CL, Brzezinski A, 
Bambrick ML, Fazio VW, Lashner BA.Modified pouchitis disease activity index: 
a simplified approach to the diagnosis of pouchitis. Diseases of Colon and Rectum. 

 
 
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2003 Jume 46(6): 748-53. 
 
6. Khalili H1, Ananthakrishnan AN, Konijeti GG, Higuchi LM, Fuchs CS, Richter JM, 
Chan AT. Measures of obesity and risk of Crohn's disease and ulcerative colitis. 
Inflamm Bowel Dis. 2015 Feb;21(2):361-8. 

 
 
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APPENDIX 1:  
MODIFIED POUCH DISEASE ACTIVITY INDEX (MPDAI) 
 
 

 
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APPENDIX 2:  
FECAL DONOR QUESTIONNAIRE 
 

 
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APPENDIX 3:  
MEDWATCH FORM 
 
   Please see attached US Food and Drug Administration Document entitled FDA 3500.  
 
 
 
APPENDIX 4:  
QUALITY OF LIFE SURVEY TOOLS 
 
 
 

 
 
 
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APPENDIX 5:  
FOOD RECALL QUESTIONNAIRE 
 
 
 

 
 
 
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