Fecal Microbiota Transplant National Registry
Conditions: Fecal Microbiota Transplantation, Clostridium Difficile Infection, Gut Microbiome
Sponsor: American Gastroenterological Association

 
 
Fecal Microbiota Transplant National Registry 
 
Protocol Date: June 20, 2017  
 
 
 
 
 
 
 
STEERING COMMITTEE 
Principal Investigators:  
Gary D. Wu, MD (Contact PI)  
Loren Laine, MD  
Colleen Kelly, MD  
 
Co-Investigators: 
Stacy Kahn, MD (NASPGHAN) 
Thomas Moore, MD (IDSA) 
David Rubin, MD (CCFA) 
James Lewis, MD (clinical epidemiology) 
Ashish Atreja, MD (information technology) 
 
 
 
 
AGA Administrative Contact:  
Sonya Serra, MSc 
Senior Director, Registry Development and Integrity 
AGA Institute  
 
Email: sserra@gastro.org  
Phone: 301-941-2616 
 

ii 
 
PROTOCOL SUMMARY 
This document complies with requirements of the Declaration of Helsinki, International Harmonized Standards: 
EN ISO 14155-1 and ISO 14155-2:2003(E) and with 21 CFR Parts 50, 54, 56, and 812.  
 
Title: 
Fecal Microbiota Transplantation National Registry 
Précis: 
A national data registry of patients receiving fecal microbiota 
transplantation (FMT) or other gut-related-microbiota products 
designed to prospectively assess short and long-term safety and 
effectiveness  
Mission: 
To expand knowledge and optimize practice in the 
transplantation of fecal microbiota or other gut-related-
microbiota products.  
Goals: 
To assess short-term and long-term safety  
To assess effectiveness 
To gather information on practice in North America.  
To promote scientific investigation 
To aid practitioners and sponsors in satisfying regulatory 
requirements 
 
Population: 
All patients receiving FMT or other gut-related-microbiota 
products and the donors providing specimens for the enrolled 
patients’ FMT. Patients will be enrolled regardless of race, 
gender, ethnicity, or age.  
Number of Sites: 
75 
Number of Patients 
4,000 
Subject 
Participation 
Duration: 
10 years 
 
 
 
 
 

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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the International Conference on Harmonisation 
guidelines for Good Clinical Practice (ICH E6), the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), and the NIDCR Clinical Terms of Award. All personnel involved in 
the conduct of this study have completed human subjects’ protection training.  
 
SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and provides the 
necessary assurances that this study will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and applicable US federal regulations and ICH guidelines. 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
20JUN2017 
 
Name: 
Gary D. Wu, MD 
 
Title: Co-Director, Penn-CHOP Microbiome Program 
Signed:  
 
Date: 
20JUN2017 
 
Name: 
Loren Laine, MD 
 
Title: Professor of Medicine and Director of Clinical Research, Section of Digestive 
Diseases, Yale School of Medicine 
Signed: 
 
Date: 
20JUN2017 
 
Name: 
Colleen Kelly, MD 
 
Title: Assistant Professor of Medicine, Division of Gastroenterology, Warren Alpert 
Medical School of Brown University 
 

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TABLE OF CONTENTS 
 
 
PAGE 
PROTOCOL SUMMARY .......................................................................................................................................................... II 
STATEMENT OF COMPLIANCE ......................................................................................................................................... III 
TABLE OF CONTENTS ............................................................................................................................................................. 1 
LIST OF ABBREVIATIONS ..................................................................................................................................................... 4 
1 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ............................. 5 
1.1 
Background Information ........................................................................................................................... 5 
1.2 
Prior Literature and Studies ..................................................................................................................... 5 
1.3 
Rationale ........................................................................................................................................................... 9 
1.4 
Potential Risks and Benefits ..................................................................................................................... 9 
1.4.1 
Potential Risks ................................................................................................................................ 9 
1.4.2 
Potential Benefits .......................................................................................................................... 9 
2 
OBJECTIVES.................................................................................................................................................................. 10 
2.1 
Study Objectives ......................................................................................................................................... 10 
2.2 
Rationale for Study Objectives Measures ........................................................................................ 10 
2.2.1 
To assess short-term and long-term safety ..................................................................... 10 
2.2.2 
To characterize effectiveness of FMT and other gut related microbiota 
products ......................................................................................................................................... 10 
2.2.3 
To gather information on practice in North America ................................................. 11 
2.2.4 
To promote scientific investigation .................................................................................... 11 
2.2.5 
To aid practitioners and sponsors in satisfying regulatory requirements ........ 11 
3 
STUDY DESIGN ............................................................................................................................................................ 11 
3.1 
Overview Study Design Summery ....................................................................................................... 11 
3.2 
Site Selection ................................................................................................................................................ 12 
4 
STUDY ENROLLMENT ............................................................................................................................................. 12 
4.1 
Subject Inclusion Criteria ....................................................................................................................... 12 
4.1.1 
Recipient Inclusion Criteria ................................................................................................... 12 
4.2 
Subject Exclusion Criteria ...................................................................................................................... 13 
4.3 
Strategies for Recruitment and Retention ....................................................................................... 13 
4.4 
Subject Withdrawal ................................................................................................................................... 13 
4.4.1 
Early Withdrawal of Participants ........................................................................................ 13 
4.4.2 
Data Collection and Follow-up of Withdrawn Participants ...................................... 13 
4.5 
Costs and Payments .................................................................................................................................. 13 
5 
STUDY PROCEDURES AND EVALUATIONS ..................................................................................................... 14 
5.1 
Data Elements.............................................................................................................................................. 14 
5.2 
Study Specific Biospecimens and Biorepository Sub-Study..................................................... 14 
6 
ASSESSMENT OF SAFETY ....................................................................................................................................... 14 
6.1 
Adverse Events ........................................................................................................................................... 14 
6.2 
Classification of Events ............................................................................................................................ 15 
6.2.1 
Relatedness ................................................................................................................................... 15 
6.2.2 
Expectedness ............................................................................................................................... 16 

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6.3 
Serious Adverse Events (SAE) .............................................................................................................. 16 
6.4 
Reporting Procedures .............................................................................................................................. 16 
7 
REGISTRY OVERSIGHT ............................................................................................................................................ 17 
7.1 
Steering Committee .................................................................................................................................. 17 
7.2 
Observational Study Monitoring Board ............................................................................................ 17 
7.3 
Data Access and Publication Committee .......................................................................................... 17 
7.4 
Funding Sources and Conflicts of Interest ....................................................................................... 18 
8 
STATISTICAL PLAN ................................................................................................................................................... 19 
8.1 
Sample Size Determination and Power ............................................................................................ 19 
8.2 
Interim Monitoring and Early Stopping ........................................................................................... 19 
8.3 
Statistical Methods .................................................................................................................................... 19 
9 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................................................................... 20 
9.1 
Confidentiality and Security .................................................................................................................. 20 
9.2 
Data Access ................................................................................................................................................... 21 
9.3 
Training .......................................................................................................................................................... 22 
9.4 
Records Retention ..................................................................................................................................... 22 
10 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................................... 22 
10.1 
Ethical Standard ......................................................................................................................................... 22 
10.2 
Institutional Review Board .................................................................................................................... 22 
10.3 
Informed Consent Process ..................................................................................................................... 22 
10.4 
Inclusion of Women, Minorities, and Children (Special Populations) ................................. 23 
11 
PUBLICATION POLICY ............................................................................................................................................. 23 
12 
REFERENCES ............................................................................................................................................................... 24 
Supplement 1.  Donor/Recipient Screening and FMT Technique Data Elements 
(characteristics to be collected once at initiation of site) ......................................................... 27 
Supplement 2. FMT Donor Questionnaire Data Elements ........................................................................ 31 
Supplement 3. FMT Treatment Indications and Baseline Donor/Recipient Characteristics ..... 33 
Supplement 4. FMT Effectiveness Outcomes ................................................................................................. 36 
Supplement 5. FMT Short-term Adverse Outcomes (within 30 days)................................................. 38 
Supplement 6. FMT Long-term Adverse Outcomes (up to 2 years by physician report and 
10 years by patient report) .................................................................................................................... 39 
APPENDIX A: BIOREPOSITORY SUB-STUDY PROTOCOL ...................................................................................... 40 
1. 
Facilities ......................................................................................................................................................... 40 
2. 
Estimated Duration of the Study ......................................................................................................... 40 
3. 
Specific Aims ................................................................................................................................................ 40 
4. 
Background and Significance ................................................................................................................ 40 
5. 
Research Design and Method ................................................................................................................ 41 
6. 
Human Subjects .......................................................................................................................................... 41 
7. 
Recruitment and Procedures Preparatory to Research ............................................................. 42 
8. 
Informed Consent ...................................................................................................................................... 42 
9. 
Alternatives to Study Participation .................................................................................................... 42 
10. 
Potential Risks ............................................................................................................................................. 42 
11. 
Risk Management Procedures and Adequacy of Resources .................................................... 42 

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12. 
Privacy and Confidentiality Considerations Including Data Access and 
Management................................................................................................................................................. 42 
13. 
Potential Benefits ....................................................................................................................................... 42 
14. 
Risk/Benefits Ratio ................................................................................................................................... 43 
15. 
Expense to Participate ............................................................................................................................. 43 
16. 
Compensation for Participation ........................................................................................................... 43 
17. 
Privileges/Certifications/Licenses and Research Team Responsibilities .......................... 43 
18. 
Bibliography ................................................................................................................................................. 43 
 
 
 

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LIST OF ABBREVIATIONS 
21 CFR 11 
Food and Drug Administration’s 21 Code of Federal Regulations Part 11, Electronic 
Records; Electronic Signatures 
ADaM 
Analysis Data Mode 
AE 
Adverse Event 
AGA 
American Gastroenterological Association 
CCFA 
Crohn’s &Colitis Foundation of America 
AHRQ 
Agency for Healthcare Research and Quality 
CDASH 
Clinical Data Acquisition Standards Harmonization 
CDC 
United States Center for Disease Control and Prevention 
CDI 
Clostridium difficile infection 
CDISC 
Clinical Data Interchange Standards Consortium 
CFR 
Code of Federal Regulations 
CRO 
Contract research organization 
CSUCI 
Computerized Systems Used in Clinical Trials 
DEFINE.Xml 
metadata model of SDTM, ADaM in extensible markup language 
eCRF 
Electronic Case Report Form 
eDC 
Electronic Data Capture 
ePRO 
Electronic Patient Reported Outcomes 
EU Annex 11 
EudraLex Volume 4 Annex 11 Computerised Systems (European rules for electronic 
records in clinical research)  
FDA 
United States Food and Drug Administration 
FMT 
Fecal Microbiome Transplantation  
GCP 
Good Clinical Practices 
HIPAA 
Health Information Portability and Accountability Act 
IBD 
Inflammatory Bowel Disease 
IBS 
Irritable Bowel Syndrome 
ICH 
International Conference on Harmonization 
IDSA 
Infectious Disease Society of America 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
NASPGHAN 
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 
PI 
Principal Investigator 
OSMB 
Observational Study Monitoring Board 
SAE 
Serious Adverse Event 
SDTM 
Standard Data Tabulation Mode 
SEND  
Standard for Exchange of Nonclinical Data 
 
 
 

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1 INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE  
1.1 Background Information  
The gut microbiome functions in a symbiotic relationship with the human body at a level of 
complexity akin to an organ or tissue. Recent advancements in genome sequencing technology have 
been used to identify the tremendous diversity of these microorganisms and the ability to analyze 
metadata has opened a new frontier for research into the role of the gut microbiome in health and 
disease. It is now well appreciated that intestinal microbiota constitute a microbial organ that is 
integral to overall host physiology, including pivotal roles in metabolism and immune system 
function1. Initial investigations have demonstrated that alterations in the gut microbiome 
(dysbiosis) may play a role in a number of gastrointestinal and non-gastrointestinal disorders (e.g., 
Clostridium difficile infection (CDI), inflammatory bowel disease (IBD) , irritable bowel syndrome 
(IBS), nonalcoholic fatty liver disease, obesity, diabetes, metabolic syndrome, cardiovascular 
disease, cancer)2.  
The first clinical therapeutic application of this knowledge has been the use of fecal microbiota 
transplantation (FMT). FMT involves administration of fecal material (containing intestinal 
microbiota) from a healthy individual (donor) to treat dysbiosis and restore beneficial intestinal 
flora and phylogenic diversity. The transfer of these highly complex whole communities of 
microorganisms has been shown to result in durable changes in the recipient3 and careful donor 
eligibility and screening protocols are recommended to minimize the risk of transmission of 
infectious disease or other conditions associated with dysbiosis. FMT has proven to be beneficial in 
the treatment of recurrent CDI in numerous case series4 and a recently published randomized 
controlled trial5. Because of recent trends in the incidence and severity of CDI and the growing body 
of literature, including current treatment guidelines, which support FMT, the number of physicians 
who perform FMT in the United States is growing. There are ongoing efforts to refine the process of 
FMT, with stool banks to supply donor material and commercially available encapsulated 
formulations both in the immediate future. Furthermore, investigations of FMT for the treatment of 
other conditions, such as IBD, are underway.  
1.2  Prior Literature and Studies 
The gut microbiota in health and disease: Human microbiomes are very distinctive amongst 
various body sites and are composed of bacteria and other microorganisms, including prokaryotic 
organisms such as Archaea, microeukaryotes such as fungi, and viruses (principally 
bacteriophages). In this protocol, the term “microbiota” will denote the compilation of bacterial 
microorganisms within a specific environment whereas the “microbiome” refers to the bacterial 
taxa and their collective genomes. The human gut microbiota is a densely populated bacterial 
community with approximately 1017 organisms per gram of fecal weight composed of over a 1000 
species, most of which are obligate anaerobes7,8, with a collective genome size 150-fold greater than 
that of its human host7. Although there are over 50 bacterial phyla on Earth, human-associated 

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bacteria largely belong to one of four phyla, Actinobacteria, Firmicutes, Proteobacteria, and 
Bacteroidetes. Mammalian hosts and their gut microbiota have coevolved to exist in a mutualistic 
relationship where the hosts provide a uniquely suited environment in return for physiological 
benefits provided by the gut microbiota3. Examples of the latter include the fermentation of 
indigestible carbohydrates to produce short chain fatty acids that are utilized by the host, 
biotransformation of conjugated bile acids, synthesis of certain vitamins, degradation of dietary 
oxalates, urease-mediated hydrolysis of urea that is important in host nitrogen balance, and 
education of the mucosal immune system9.  
Despite the importance of the gut microbiota in maintaining the health of the host, growing 
evidence suggests that it may also be an important factor in the pathogenesis of a variety of 
diseases, particularly those that have shown a rapid increase in incidence over the past few 
decades. These include type 1 and type 2 diabetes mellitus, atherosclerosis, asthma, colon cancer, 
inflammatory bowel disease (IBD), and autism10. Advances in genomic technology, principally DNA 
sequencing and SNP mapping used for genome-wide association studies, combined with 
biocomputational algorithms, have revealed the host genetic underpinnings of these complex 
disease processes. In most circumstances, the contribution of host genetics to disease development 
is well under 50%, implicating the importance of environmental influences11. The observation that 
these diseases have shown a steadily increasing incidence over the past several decades, the 
geographic distribution of disease clustering in industrialized nations, and immigration studies 
revealing the adoption of disease risk of the host country within 1 or 2 generations, emphasize the 
importance of environment in the pathogenesis of these diseases. The notion that an alteration in 
the composition of the gut microbiota as a possible etiologic factor in the predisposition to 
immunologically-mediated disease has been proposed as one of the environmental factors that may 
play a role in the increasing incidence of the diseases associated with the gut microbiota mentioned 
previously12.   
Dramatic advances in DNA sequencing technology as well as the development of ever more 
sophisticated biocomputational tools to analyze massive datasets continue to fuel research into the 
gut microbiome. The future challenge in this field of research will be to address a number of 
fundamental questions relevant to human health and disease including: 1) Is there a microbiome 
associated with human health—the “healthy gut microbiome”; 2) Are there causal relationships 
between the gut microbiome and human disease?; 3) Is there a role for non-bacterial gut microbes 
(i.e., microeukaryote (yeast), viruses, and Archaea) in human health and disease?; and 4) What is 
the optimal method to alter the gut microbiota in a way that is beneficial to humans with disease? 
The answers to these, and other fundamental questions in the field of gut microbial ecology await 
further studies in human subjects in whom clinical metadata is carefully collected together with 
continued investigation in animal models.  Rapidly advancing broad-based technologies in addition 
to DNA sequencing, such as transcriptomics, proteomics, and metabolomics, will allow assessment 
not only of the structure but also the function of the gut microbiome. Ultimately, the answers to 
these questions could lead to a fundamental shift in the way that we treat many common diseases. 
The clinical data collected in the FMT registry and its association with data generated from the 
analysis of fecal samples stored in a biorepository will provide one of the first opportunities to 
address some of these questions in a robust and systematic way, using CDI as a paradigm. 

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It is ironic that, juxtaposed to these technological advances and our rapidly increased 
understanding of the gut microbiome, is the re-emergence13 of FMT. FMT is the delivery of stool 
from a healthy pre-screened donor to an individual with disease with the goal of restoring a healthy 
gut microbiome and correcting the underlying dysbiosis14-16. This “shot-gun” approach has proven 
to be a highly effective therapeutic modality for recurrent CDI17. The use of FMT has highlighted a 
gap in our current knowledge base. The availability of the therapeutic substrate (feces), together 
with the ease of administration, has advanced the practice in the field of gut microbiota modulation 
much more rapidly than our scientific understanding in the field. In addition the early adoption and 
expansion of FMT in clinical practice has bypassed the standard investigatory pathway (e.g., large 
randomized trials) that typically contributes important short- and long-term safety data. From a 
scientific standpoint, the success of FMT in the treatment of CDI is an important proof-of-concept 
that dysbiosis can be modified to treat a human disease, a notion that might extend to other disease 
processes such as IBD18 and metabolic syndrome19. On the other hand, associations between the gut 
microbiota and a number of human diseases with cause-and-effect relationships demonstrated in 
animal models raise legitimate safety concerns about the use of FMT that extend beyond pathogen 
transmission20. We believe that our proposed FMT registry and its associated biobank will be of 
significant value in enhancing the scientific value of FMT to the gut microbiome research field while 
also helping to address safety concerns. Indeed, two of the four goals of the registry are: 1) To 
assess short-term and long-term safety and 2) To promote scientific investigation. 
FMT for the treatment of recurrent CDI: Since approximately 2000, there has been an alarming 
increase in the incidence and severity of CDI21,22. Cases of CDI nearly doubled from 98,000 in 1996 
to 178,000 in 200323, and the unadjusted case-fatality rate increased from 1.2% in 2000 to 2.3% in 
2004. It is estimated that 3 million cases of CDI occur each year, obligating annual excess hospital 
cost of 3.2 billion dollars24. Equally concerning has been the increased incidence of community-
associated CDI which now is being reported in populations previously believed to be at low risk, 
including children25-26, peripartum women, and healthy individuals without a history of antibiotic 
use21. C. difficile recurrence is a common management problem and occurs in up to 20% of patients 
after initial treatment27,28 . Patients who experience one recurrence have a 40% risk of an additional 
recurrence and those with 2 or more episodes face a 60% risk of another episode21,29. While the 
first recurrence is generally treated with a second course of metronidazole or vancomycin, current 
guidelines30 recommend a tapering course of oral vancomycin. Treatment options are limited for 
the significant number of patients who continue to experience additional CDI recurrences. 
Interventions that have been used, but with little or no data to support efficacy, include intravenous 
immunoglobulin, rifaximin, nitazoxanide, and probiotics15. FMT is performed to restore the 
phylogenetic diversity of normal stool and the associated “colonization resistance” that enables 
normal intestinal flora to resist overgrowth of C. difficile31. Numerous case reports and 
retrospective case series have demonstrated benefit of FMT in patients with severe or recurrent 
CDI with a mean cure rate of 89% for the approximately 300 cases reported in the world 
literature14,32-41. A randomized controlled trial published in 2013 confirmed the high efficacy of 
FMT40. Methods used to administer FMT include nasogastric and nasointestinal tubes, upper 
gastrointestinal (GI) tract endoscopy, retention enemas, sigmoidoscopy, and colonoscopy34-37,43,44.  

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The proof of concept regarding the role of the gut microbiota in human disease provided by the 
success of FMT for refractory CDI45 has catalyzed efforts to extend this approach to other conditions 
that appear to have strong microbial pathogenic mechanisms, including metabolic syndrome19 and 
IBD18. For example, in a double-blind, controlled trial, males 21-65 years old with BMI >30kg/m2 
and fasting plasma glucose >5.6 mmol/liter were randomized to receive FMT from either lean male 
volunteers or from themselves. Fecal transplantation from the lean donors improved peripheral 
insulin sensitivity during the short period in which this parameter was followed19.  Also, a recent 
randomized trial in 70 patients with ulcerative colitis showed a significant benefit of FMT in 
induction of remission18  
Actual and theoretical risks of FMT and the need for regulation46: There has been mounting 
demand from clinicians and patients to use FMT for many applications, including conditions where 
the role of the microbiota in disease pathogenesis is unclear. In the face of this demand, and 
motivated by concerns about safety, the U.S. Food and Drug Administration (FDA) initially ruled 
that FMT is both a drug and a biologic that has not currently received approval for any clinical 
indications. As a result, the FDA required an investigational new drug (IND) application for FMT to 
be used for any medical indication. More recently, however, the FDA decided to exercise 
“enforcement discretion” regarding INDs for the use of FMT in adults with CDI that is not 
responsive to standard therapies47. Importantly, FMT may not be used for any indication other than 
unresponsive CDI without an IND.  
While the value of FMT in treating recurrent CDI is clear, its potential long-term detrimental 
consequences are not known. The gut microbiota is a complex consortium with many components 
that have never been characterized. A priori knowledge is not available regarding the impact of 
transferring these complex communities from one individual to another, although many studies in 
mice indicate that the composition of the gut microbiota can affect host susceptibility to diseases. 
Recall the unexpected consequence of the hepatitis C virus epidemic from the transfusion of 
contaminated blood before its presence was recognized. Similarly, the transmission of HIV to 
thousands of hemophiliacs by contamination of a biologic produced from human materials serves 
as another illustration of how the ’precautionary principle’ needs to be applied to FMT46. Patients 
need to be informed of potential risks and consent to the procedure. Protocols need to be 
developed about donor sample preparation, characterization, archiving (so that follow-up analyses 
can be performed), and host preparation/administration/dosing. Registries need to be established 
for collection of data on donor and recipient characteristics, FMT techniques, and short-term and 
long-term outcomes. Best practices for FMT need to be established, and critically evaluated, 
clinically-relevant recipient responses to FMT, both beneficial and adverse, need to be defined and 
monitored.  
Current state of knowledge in the U.S. on the practice of FMT: Despite the safety concerns about 
transferring a complex and undefined microbial living microbial community from one human to 
another, there is very little current information about practice of FMT in the U.S. Critical 
methodologic data such as donor/recipient screening, fecal preparation, modality of delivery, and 
patient consent practices are lacking. Information about the effectiveness of FMT as well as both 
short- and long-term safety data are not systematically collected with the only available 

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information being case reports published in the literature. The only currently available modality to 
capture adverse outcome data for FMT is through the FDA Medwatch portal, a mechanism 
constrained by reporting bias. Remarkably, the number of FMT practitioners as well as number of 
patients being treated in the US are also unknown. Based on self-reporting, there are at least 90 
FMT sites but the number may be much greater. Based on this information void, national societies 
have attempted to provide guidance to practitioners through published guidelines and editorials48-
50 but the degree of adherence to these recommendations is unknown.   
1.3  Rationale 
FMT and future methods of providing gut-related microbiota for treatment of disease are in their 
infancy, and a great number of questions exist regarding technique, practice, safety, and efficacy. 
Currently, the FDA is exercising enforcement discretion for IND requirements for use of FMT to 
treat CDI not responding to standard therapies provided treating physicians obtain informed 
consent from the patient.  
As the practice of FMT and related therapeutic methods rapidly expands in the U.S., it is crucial to 
assess short-term and long-term safety, to determine the effectiveness in “real-world” settings, and 
to identify the techniques being used by practitioners in an attempt to standardize and optimize 
practice in the future. Perhaps the greatest concern is to determine if there may be long-term safety 
consequences of FMT that are not currently recognized. For example, can transfer of fecal 
microbiota lead to chronic diseases such as diabetes, obesity, or cardiovascular disease? Animal 
models have suggested such a possibility, as transfer of specific phenotypes (e.g., obesity) have 
been demonstrated after fecal transplant in mice52. 
1.4 Potential Risks and Benefits 
1.4.1 Potential Risks  
There are no risks of physical harm associated with participation in the data registry. Participation 
in the registry does involve the potential risk of breach of confidentiality of medical information 
and associated privacy of the participants.  
1.4.2 Potential Benefits  
There is no expected direct health benefit immediately associated with a patient’s participation in 
the registry. However, the use of the information from the registry may provide future benefit to 
healthcare providers and patients who require treatment for CDI and other conditions that may be 
associated with dysbiosis by expanding knowledge regarding FMT and other gut-related microbiota 
products with the goal of optimizing practice. The potential future benefits include determining if 
short-term and long-term safety issues exist, characterizing effectiveness, establishing best 
practices for FMT, providing a resource for investigators to conduct research related to FMT and 
the gut microbiome, and assisting practitioners and sponsors in satisfying regulatory requirements. 

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2 OBJECTIVES  
2.1 Study Objectives 
The overarching goal of the FMT registry is to expand knowledge and optimize practice in the 
transplantation of fecal microbiota or other gut-related-microbiota products. 
Primary Objective: To assess short-term and long-term safety of FMT and other gut-related-
microbiota products. 
Secondary Objectives:  
• 
To characterize effectiveness of FMT and other gut-related-microbiota products.  
• 
To gather information on FMT practice in North America 
• 
To promote scientific investigation. 
• 
To aid practitioners and sponsors in satisfying regulatory requirements. 
2.2 Rationale for Study Objectives Measures  
2.2.1 To assess short-term and long-term safety  
The safety of FMT is currently the greatest concern related to its use, and characterizing the safety 
of FMT and subsequent gut-related-microbiota products is the primary goal of the Registry. Short-
term adverse events (AEs) relate primarily to the method of delivery (e.g., colonoscopy) and to 
acute infections or other adverse events from the donor fecal material and should be readily 
definable and quantifiable. Of greater concern and uncertainty is the possibility of long-term AEs. 
The human-to-human transfer of feces may be associated with long-term health risks to the 
recipient because the gut microbiota is composed of many components that have not been 
characterized and can change over time in ways that cannot be currently predicted. It is imperative 
to determine if FMT leads to unintended development of serious conditions due to the transfer of 
gut microbiota. In addition to infections, the possibility that gut microbiota associated with a 
disease phenotype (e.g., obesity, diabetes, cardiovascular disease) will be transplanted and result in 
chronic disease in recipients must be assessed. A prospective registry in a large sample of patients 
with long-term follow-up is the only practical method to achieve this aim at present.  
2.2.2 To characterize effectiveness of FMT and other gut related microbiota products 
Current information on the efficacy of FMT in treating clinical disease is restricted to case reports, 
case series, and one randomized trial in recurrent CDI. Furthermore, only short-term follow-up is 
generally provided in these reports. Determining the short-term and long-term effectiveness in 
real-world practice is crucial and assessing variations in efficacy outcomes related to methodology 
will enable standardization and optimization of FMT practice.  

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2.2.3 To gather information on practice in North America  
FMT and future methods of providing gut-related microbiota for treatment of disease are in their 
infancy. Currently there is a lack of standardization in all aspects of FMT, and given a lack of current 
regulatory requirements for reporting, the methodology being employed (e.g., screening, 
preparation, delivery, indications, follow-up) is unclear. Obtaining information on current FMT 
methods in North America is an important first step in characterizing FMT practice with the future 
goal of standardizing and optimizing FMT.  
2.2.4 To promote scientific investigation 
A large FMT registry will provide an unprecedented and rich resource for investigators to advance 
the science of the gut microbiome in health and disease. The registry database will be available to 
investigators, with study proposals submitted for review by a Data Access and Publications 
Committee. Furthermore, this registry data will link to a biobank of fecal samples from the donor 
(one time) as well as recipient (before and after FMT). Together with the clinical metadata collected 
within the registry, information from analysis of specimens in the biobank will enhance short- and 
long-term safety surveillance as well as be a rich source of data to investigate modulation of the 
human gut microbiome. 
2.2.5 To aid practitioners and sponsors in satisfying regulatory requirements 
The FDA is currently determining the appropriate regulatory requirements for physicians 
performing FMT, exercising enforcement discretion regarding an IND requirements for use of FMT 
in treatment of CDI unresponsive to standard therapies. Participation in the FMT Registry provides 
an excellent method of oversight, helping to prevent marked departures in methodology from 
recommended practices, improve safety for patients, and gather data for quality improvement and 
future regulatory requirements. In addition, gut-related-microbiota products, from processed stool 
to defined microbiota consortia, require submission for regulatory approval. The Registry may 
function as an important vehicle for sponsors of gut-related microbiota products to satisfy pre-
approval and post-approval assessment of product safety and efficacy.  
3 STUDY DESIGN  
3.1 Overview Study Design Summery  
This registry will prospectively enroll 4,000 patients who undergo FMT at 75 sites throughout 
North America. Information on FMT methodology employed (e.g., screening of donor and recipient, 
preparation, FMT delivery) will be collected from each site. The indication for FMT as well as 
baseline information on recipient will also be collected. Following FMT, patients will be followed at 
regular intervals up to 10 years post FMT. This will include follow-up information from the 
patient’s healthcare provider at 1 month, 6 months, 1 year, and 2 years after FMT as well as direct 
communication with patients at least annually up to 10 years after FMT. Follow-up information 
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Anticipating changes in therapy from current FMT to use of other gut-related microbiota products 
in coming years, the Registry will be constructed with the flexibility to collect methodological and 
follow-up clinical information for all forms of gut-related-microbiota products and for a variety of 
indications besides CDI and IBD.  
3.2 Site Selection  
Sites currently performing FMTs will be allowed to participate in the FMT registry. Sites may utilize 
any method of FMT treatment or may provide other gut-related microbiota products.   
Sites selected to participate in the registry must demonstrate that all study staff have completed 
human subjects protection and HIPAA training prior to enrollment. Study staff must pass training 
on informed consent procedures, the electronic case report form (eCRF) system for data recording, 
and reporting procedure for unexpected events. Sites must demonstrate proper data protection 
procedures prior to participant enrollment.  All site Principal Investigators must sign an 
Investigators Agreement and confirm IRB approval prior to site activity starting.  
Sites will be chosen based on the following criteria: 1) FMT volume; 2) geographic location; 3) 
ability and willingness to comply with the requirements of registry participation; 4) have an IRB-
approved protocol.  In the initial phase, we will include the centers of the investigators on this 
proposal (n=5) and 20 centers from our listserv of 70 centers representing thought leaders in FMT 
with an interest in clinical investigation.  To enhance representation of a geographically diverse 
population in the registry, centers will be related to their location in population-based regions.  
Using the projected number of FMTs at each center, we will enroll the number of centers in each 
region required to achieve a proportion of FMTs in the registry from a region to approximately 
mirror the proportion of the U.S. population in that region. 
4 STUDY ENROLLMENT 
4.1 Subject Inclusion Criteria  
Participants will be eligible for participation regardless of age, race, ethnicity, or gender. Pediatric 
patients may participate if consent is given by a guardian.  
4.1.1 Recipient Inclusion Criteria  
• 
Ability to give informed consent  
• 
Receiving FMT or other gut-related microbiota product within 90 days after providing 
consent 
• 
Access to internet and/or telephone 
 
 
 

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4.1.1.1 Donor Inclusion   
• 
Ability to give informed consent 
• 
Providing stool sample for FMT 
4.2 Subject Exclusion Criteria  
• 
Incarceration 
4.3 Strategies for Recruitment and Retention 
Participants who are being seen in clinical practice as an FMT recipient (or FMT donor) or as a 
recipient of other gut-related-microbiota products will be approached in a private room to receive 
information about the registry protocol, the option to participate in a biorepository sub-study, 
review the informed consent documents, and to ask questions and review the risks and benefits of 
participation. Participants will have as much time as they would like to review the documents and 
ask questions regarding participation.  
4.4 Subject Withdrawal 
4.4.1 Early Withdrawal of Participants 
Participants may end their participation at any time by notifying the study staff of their desire to 
halt participation. This may be done in writing or by secure internet connection. Registry mailing 
address and electronic address will be provided to all participants.  
4.4.2 Data Collection and Follow-up of Withdrawn Participants 
When participants notify study staff that they no longer wish to participate, study staff will request 
final-visit information from the participant and their healthcare provider. If the participant informs 
the study staff that they wish to withdraw consent, no further data will be sought from them or 
their healthcare provider. Data that was previously collected when the patient was actively enrolled 
will be retained in the registry. 
4.5 Costs and Payments 
This is not a clinical treatment study and all costs associated with the care and treatment of patient 
receiving FMT and follow-up will be paid by the patient or their insurance provider. No costs will be 
incurred by participants related to participation in the Registry. Continued patient participation 
will be encouraged with a $10 gift card for providing health information each year beginning 1 year 
post-FMT. 

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5 STUDY PROCEDURES AND EVALUATIONS 
The only study procedure will be data collection regarding methodology of FMT, characteristics and 
health outcomes of recipients of FMT or other gut-related-microbiota products, and baseline 
characteristics of donors of stool for FMT.  
5.1 
Data Elements 
Data elements that may be collected for the FMT registry are shown in Supplements 1-6.  In order 
to make the data elements as broad and inclusive as possible, the FMT Registry Steering Committee 
developed the data elements based on current guidelines and published recommendations48-50, 
their own treatment protocols/experience, and feedback from 15 additional large FMT practice 
sites. Supplement 1 details the data elements related to FMT technique including donor and 
recipient screening.  For sites that employ a donor questionnaire, Supplement 2 provides potential 
questions used on a questionnaire, based on those used for blood transfusion.  Supplement 3 shows 
the data elements for baseline characteristics of donors and recipients and for FMT treatment 
indications, while Supplement 4 provides effectiveness outcomes data elements.  Finally, 
Supplements 5 and 6 detail data elements for short-term and long-term safety outcomes.  Patients 
will be followed at regular intervals for up to 10 years after FMT for pre-defined and spontaneously 
reported adverse events and for pre-defined outcomes of effectiveness.  Investigators will enter 
follow-up data at 1 month, 6 months, 1 year and 2 years post-FMT, and patients will then provide 
data annually up to 10 years.    
5.2 
Study Specific Biospecimens and Biorepository Sub-Study 
No biospecimens will be collected as part of this registry. However, participants have the option to 
enroll in a Biorepository Sub-Study and provide stool specimens to be stored in a biorepository that 
will be linked to their registry data.  The biorepository will be maintained by the American Gut 
Project at University of California at San Diego. Currently, we plan to link data from at least 1,000 
FMT procedures for participants in the registry to this biorepository, with 3 stool specimens for 
each FMT: a donor stool specimen and 2 recipient stool specimens (before and after FMT).  The 
Biorepository Sub-Study protocol is described in Appendix A. 
6 ASSESSMENT OF SAFETY 
Details about participant risk and potential benefits are detailed in informed consent. AEs 
experienced by participants involved in this registry will be reported to the site’s IRB in accordance 
with their procedures. 
6.1 Adverse Events  
Based on numerous case reports and small clinical studies in the literature, it appears that FMT for 
refractory CDI is generally well-tolerated and safe, although occasional adverse events (e.g., febrile 

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episodes) have been reported39,50. Importantly, a prospective systematic evaluation of both 
immediate and short-term predefined adverse outcomes in a large number of patients undergoing 
FMT is currently lacking. In the absence of any consensus guideline on practice standards for FMT 
in the U.S. and the lack of regulatory oversight for the treatment of refractory CDI, the committee 
has learned through polling of sites performing FMT that there is a wide variation in the practice of 
FMT. This variance in practice also raises potential concerns about risks for both short-term and 
long-term risks. As discussed in section 5.1, to broadly capture adverse outcomes in recipients of 
FMT that may be indicative of a safety concern, we have developed two data entry fields: 1) Short-
Term Adverse Outcomes (within 30 days)—Supplement 5, and 2) Long-term Adverse Outcomes 
(up to 2 years reported by the physician and 10 years reported by the patient)—Supplement 6. 
Adverse event information will be provided by the FMT provider site at four time points post-FMT: 
1 month, 6 months, 1 year, and 2 years. In addition, patients will be contacted directly by email and 
text at least annually for up to 10 years to provide follow-up information via a dedicated portal 
maintained by the Icahn School of Medicine at Mt. Sinai. 
6.2 Classification of Events 
6.2.1 Relatedness 
The site Investigator will assess the relationship of 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: 
• 
Possible alternative causes of the SAE, including the disease under treatment, pre-existing 
conditions, concomitant use of other drugs, and presence of environmental or genetic 
factors. 
• 
The temporal association between FMT exposure and onset of the SAE. 
• 
Whether the manifestations of the SAE are consistent with known actions or theoretical 
toxicity of FMT. 
 
The causal relationship between FMT and the SAE will be assessed using one of the following 
categories. 
1. 
Not Related:  
• 
Temporal relationship is lacking (e.g., the event occurred before FMT); or 
• 
Other causative factors explain the event (e.g. pre-existing condition, other concomitant 
treatment); 
2. 
Possibly Related:  
• 
Positive temporal relationship (e.g., the event occurred within a reasonable time frame 
following FMT); and 
• 
The SAE is possibly explained by FMT and/or, and there is a lack of other causal factors.  
3. 
Related:  
• 
Positive temporal relationship (e.g., the event occurred within a reasonable time frame 
following FMT); and 
• 
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6.2.2 Expectedness 
Related or possibly related SAEs will be assessed as to whether they were expected or unexpected 
based on current knowledge regarding the effects of FMT. Events known to be associated with FMT, 
CDI, or IBD include the following: 
o Diarrhea 
o Constipation 
o Abdominal pain 
o Fever 
o Sedation complication 
o Bleeding 
o Perforation 
o Bacterial infection 
o Viral infection 
o Fungal infection 
o Parasitic infection 
Events that are determined to be expected will be reported through the annual event summary report 
to the Sponsor and OSMB. 
6.3 Serious Adverse Events (SAE) 
The only type of adverse event that may occur related to participation in the FMT registry is breach 
of privacy/confidentiality.   
Clinical SAEs that are recorded in the registry will have the standard definition, which includes the 
following:  
• 
Death 
• 
Life-threatening (patient was at substantial risk of dying) 
• 
Hospitalization (initial or prolonged) 
• 
Disability or permanent damage 
• 
Congenital anomaly/birth defect 
• 
Other important event (may jeopardize patient and may require to prevent one of other 
outcomes) 
6.4 Reporting Procedures 
All spontaneous and pre-specified AEs reported by participants or healthcare providers will be 
recorded in the Registry database. Predefined short-term and long-term AEs are presented in 
Supplements 5 and 6.  Analyses of all AEs (including spontaneous and pre-defined AEs and SAEs) 
will be provided to the Registry Steering Committee and the OSMB at least twice yearly for their 
review. Summaries of AEs (including spontaneous and pre-defined AEs and SAEs) will be submitted 
to IRB and NIH during the annual review of the registry.  

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Breach of privacy and suspected unexpected SAEs will be reported to the Registry Steering 
Committee Chair and Co-Chair and the OSMB within 5 days of identification of the event. These 
events will also be reported to the local site IRB per local reporting criteria.  
All participants are given a toll-free number to contact the Investigators directly if they have any 
safety issues or concerns. 
7 Registry Oversight 
7.1 Steering Committee  
The FMT Registry Steering Committee will oversee the FMT Registry. This Steering Committee will 
report to the AGA Center for Microbiome Research and Education Scientific Advisory Board, which 
reports to the AGA Governing Board. The Steering Committee will be comprised of the individuals 
listed on the FMT Registry Protocol as Principal Investigators (PIs) and Co-Investigators. Two PIs, 
Drs. Laine and Kelly, will serve as the Chair and Co-Chair of the Steering Committee and will be 
responsible for the daily management of the registry and its associated activities (e.g., site selection, 
recruitment, IRB requirements, data management). The contact PI, Dr. Wu, as Chair of the AGA 
Center for Microbiome Research and Education Scientific Advisory Board will serve on the steering 
committee in an ex officio capacity. The other members of the steering committee, comprised of the 
co-investigators, include representatives of key organizations that have helped to develop the 
registry and have an interest in its execution (IDSA, NASPGHAN, CCFA) as well as experts in clinical 
epidemiology and information technology.  
7.2 Observational Study Monitoring Board  
An independent OSMB will be established to monitor the registry performance and data in order to 
protect the safety and privacy of participants and to ensure the integrity and credibility of the 
registry. OSMB members will have no involvement in the FMT registry and no vested scientific or 
financial interest in the registry. OSMB members will include a data scientist with experience in 
epidemiology and registries, and at least two other members with expertise in clinical investigation, 
FMT, and/or the gut microbiome. It is anticipated that the OSMB will meet at least twice yearly and 
will review information on the registry conduct and results, including recruitment and retention, 
deviations from registry protocol, breaches of confidentiality, characteristics of participants, and 
safety and effectiveness outcomes. The OSMB will produce minutes for each meeting and provide 
any comments or recommendations regarding registry conduct or participant safety/privacy to the 
FMT Registry Steering Committee. 
7.3 Data Access and Publication Committee  
A Data Access and Publication Committee will be established to review requests from investigators 
to access and perform analyses of registry data for purposes of scientific presentation and 
publication. This committee will ensure that the request is appropriate and within the scope of the 

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registry. It is anticipated that all appropriate requests for data will be granted. Once approved, data 
requests will be forwarded to ACI Clinical for processing. The investigators will be asked to adhere 
to the data sharing agreement, which includes credit to FMT Registry and the R24 as the source of 
the data on subsequent publications, abstracts, and other presentations. 
7.4 Funding Sources and Conflicts of Interest 
The FMT Registry is funded with a grant provided by the National Institute of Allergy and Infectious 
Diseases at the National Institutes of Health.  
All investigators are required to conduct themselves at all times in accordance with Good Clinical 
Practices. Investigators are expected to commit themselves to ethical and professional conduct of 
clinical research. Commitment to preserving the physician’s, medical community, and public’s trust 
is ensured by conducting research at the highest scientific and ethical standards. Disclosure of any 
potential conflict of interest strengthens this trust. The COI review process will be: 
  
• 
An AGA COI disclosure form and confidentiality statement is to be completed by all 
Investigators, including Steering Committee, OSMB members and Data Access and 
Publications Committee members, at the start of the project and updated at least 
annually thereafter, for 1 year post appointment/tenure. 
• 
The content of the disclosure is the responsibility of each Investigator. The 
Investigator is expected to complete the statement, sign and submit it in writing to 
the AGA prior to engaging in research. It will then be forwarded to the AGA Institute 
Ethics Committee, who will report the existence of a conflict, if present, to the 
subcommittee, committee or task force chair as appropriate.  
• 
The Ethics Committee is authorized to disqualify a candidate for Registry 
committees or the OSMB who fails to make a disclosure or who does not agree to 
resolve the conflict prior to assumption of their position. 
• 
The disclosure statement is required to be completed even if no conflict exists.  
• 
Disclosure and confidentiality statements will be held in a confidential file 
maintained by the national office. Access to the file will be available to appropriate 
AGA staff, the AGA Institute Ethics Committee, and the AGA Institute Governing 
Board only.  
• 
Members adversely affected by this policy may request the Ethics Committee review 
the issue and recommend to the Governing Board that application of the policy be 
waived for compelling reasons.  
• 
Reporting financial interest to the AGA Institute does not replace the need to comply 
with federal COI requirements. 

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8 Statistical Plan 
8.1 Sample Size Determination and Power 
As noted in the AHRQ’s Registry User’s Guide51, registries are used to provide precise estimates of 
outcomes in real-world practice and document that potential adverse events occur at less than a 
pre-specified incidence with a predefined level of confidence. Plans for the FMT registry include a 
sample size of approximately 4,000 patients, which will provide precise estimates of incidence rates 
for common and rare events. For example, if the incidence of an outcome after FMT in the Registry 
population is 5.0%, the 95% CI will be 4.4% to 5.7%, indicating a precise estimate of treatment 
effect. The planned sample size will also provide high confidence in ruling out rare adverse events. 
If an adverse event does not occur in the planned population of 4000 patients, we will have 95% 
confidence that the adverse event occurs at a rate of less than one in a thousand patients 
undergoing FMT.  
The FMT registry also will support comparative effectiveness studies focusing on different methods 
of delivery of FMT (e.g., colonoscopy, enema, upper GI endoscopy, nasogastric or nasointestinal 
tube). Statistical power for comparative effectiveness studies will depend upon the incidence of the 
outcome and the distribution of use of the different methods of delivering FMT. For example, 
assuming an outcome that occurs in one out of 1,000 FMT procedures using one delivery method, 
there would be 90% power to detect a difference between an incidence of 0.001 and 0.008 
assuming that 2,000 patients were exposed to each of the two delivery methods. For more common 
outcomes, the statistical power for specific relative risk estimate is greater. For example, with 2,000 
patients in each group there would be 90% power to detect a difference between two approaches 
for which the incidence rates of events were 3% and 5% (i.e., RR=1.67). 
8.2 Interim Monitoring and Early Stopping 
The Registry will have no formal interim analysis or early stopping plan. Regular monitoring of the 
safety and effectiveness data will be performed by the Registry Steering Committee and OSMB. 
Regular review of analyses of safety and effectiveness will occur twice yearly. In addition, breaches 
of privacy or suspected unexpected SAEs will be reported to the Registry Steering Committee Chair 
and Co-Chair and the OSMB within 5 business days after the event is identified.   
8.3 Statistical Methods 
The registry will be designed in a manner that will facilitate statistical analyses for the purpose of 
signal detection, generation of descriptive data, and the conduct of comparative effectiveness 
studies. There will be several major advantages of the registry design as opposed to a system of 
spontaneous reporting. Most importantly, a prospective cohort of patients who undergo FMT with 
collection of predefined outcomes will allow accurate estimation of incidence rates. In contrast, 
systems that rely on spontaneous reporting have incomplete numerator data and lack denominator 
data. The ability to calculate incidence rates greatly facilitates both descriptive epidemiology and 
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 As noted above, registries are used to provide precise estimates of outcomes in real-world practice 
and document that potential adverse events occur at less than a pre-specified incidence with a 
predefined level of confidence. Thus, descriptive statistics with 95% confidence intervals will be 
determined for the safety and effectiveness outcomes to provide precise estimates of incidences. As 
mentioned above, if an adverse event does not occur in the planned population of 4,000 patients, 
we will have 95% confidence that the adverse event occurs at a rate of less than one in a thousand 
patients undergoing FMT. 
To increase our ability to study unanticipated adverse events, we will include a retrospective 
control group of patients with recurrent CDI identified from insurance claims using Optum Insight 
Life Sciences, Inc data.  Using these data, we can determine the incidence of relevant outcomes in a 
group of patients with recurrent CDI treated with antibiotics rather than FMT. The incidence of 
relevant outcomes in this group can be compared to the patients treated with FMT in the registry. 
To assure the feasibility of this approach, we have conducted a preliminary analysis of these data to 
identify the number of patients who will be included in the control cohort. Recurrent CDI was 
defined as having a physician-made diagnosis of CDI (ICD-9 008.45) treated with 3 separate courses 
of antibiotics with metronidazole, vancomycin, or fidaxomicin (at least one of which were 
vancomycin or fidaxomicin).  The 3 antibiotic prescriptions had to be at least 10 days apart and the 
third course needed to be started within the 90 days following the CDI diagnosis. We identified 
4,313 patients meeting this definition with mean follow-up of 1.70 years.  The sample size should 
be sufficient to address questions on relatively rare outcomes. For example, at age 68 years (the 
median age in our control cohort), the probability of death in the next 12 months is 1.75% and the 
expected survival is 18.8 years (CDC lifetables). With an average follow-up time of 1.70 years, 
assuming equal number of subjects undergoing FMT and equal follow-up time, we would have 90% 
power to detect a hazard ratio of 0.77 for a difference in survival rates between FMT and antibiotic 
treated patients. 
As mentioned above, the FMT registry also will support comparative effectiveness studies focusing 
on different methods of delivery of FMT. Comparative effectiveness studies rely on the ability to 
adequately account for differences between the treatment groups. The FMT registry will facilitate 
this by collecting robust data on the indications for therapy and other covariates that describe the 
recipients and the methods of delivery. Such data will support standard statistical methods 
including logistic, Cox, and other regression methods, and the development of propensity scores 
and risk scores for risk adjustment.  
9 QUALITY CONTROL AND QUALITY ASSURANCE 
9.1 Confidentiality and Security 
The registry will collect only clinical data and test results. There is a theoretical risk of breach of 
confidentiality or a data security loss although exhaustive efforts will be made to minimize this 
inherent risk. All sites must demonstrate proper physical and electronic security measures in order 
to participate in the registry.  

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To protect the confidentiality of the participants it is required:  
1. Separate all direct participant identifiers (i.e., names, social security numbers, medical 
record numbers, etc.) from outcome information stored in the registry 
2. Securing in a separate location and limiting access to information linking codes assigned to 
the registry information with direct participant identifiers  
3. Limiting access to information contained within the registry to investigators and approved 
study staff 
All data from healthcare providers will be entered into the registry through the eCRF system 
maintained by Viedoc™.  The electronic data capture system is 21 CFR Part 11 compliant. All 
computers will be used to collect and send data during implementation of the study or to receive or 
store data at the central location will be password protected. A password will be required to open 
Windows® and a second, different password will be required to open the electronic data capture 
system, Viedoc™. This closed system requires a unique identification for each user.  
Electronic forms will be stored on a secure dedicated server with appropriate firewalls. The system 
will use 128- bit encryption (SSL certificate). This technology is the same as that used for online e-
commerce applications to protect consumer information such as name, address, and credit card 
details. The system has a secure login along with audit control mechanisms to meet HIPAA 
standards. Servers are scanned for viruses and systems are in place to detect attempts at 
unauthorized entry. The data base server is backed up daily internally. All transactions to the 
database are stored in archive logs as re-do data and are accessible to enable quick recovery of all 
data should the need arise. Backup files are written nightly to back up servers. Weekly, a monthly 
backup copy is stored off-site in perpetuity.  
For follow-up beyond 2 years, the ePRO system allows the registry staff to automatically contact the 
patient for follow-up information. For example, patients can receive an automatic text message or 
email that opens to a follow-up electronic questionnaire for long-term follow-up. The link to the 
ePRO also will be embedded in the patient education app that will include content (videos and 
written information) approved by the steering committee related to FMT indications, pre-
procedure checklist, potential adverse events, and post-procedure follow-up. The app will be 
maintained at Sinai AppLab, Icahn School of Medicine at Mount Sinai and will be made available to 
all FMT patients enrolled in the registry.   
9.2 Data Access 
The AGA will create a dedicated landing page for the FMT registry on its Web site, through which data 
access requests can be made. Interested investigators will be asked to submit a brief application 
including their research question(s) and requested criteria and variables. The Data Access and 
Publication Committee will review these requests to solely ensure that the request is appropriate 
and within the scope of the registry. It is anticipated that all appropriate requests for data will be 
granted. Once approved, data requests will be forwarded to ACI Clinical for processing. The 
investigators will be asked to adhere to the data sharing agreement, which includes credit to FMT 
Registry and the R24 as the source of the data on subsequent publications, abstracts, and other 
presentations. We will transmit (PHI) de-identified and aggregate data to approved applicants via 

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the web portal, along with appropriate documentation that describes the study methods and 
procedures used to collect the data, details about the codes, definitions of variables and metadata, 
variable field locations and other information relevant to the data use. Payment solely to cover the 
costs of data retrieval will be required.   
 
Data from the eDC deployed FMT registry database will receive secure data transfers from the Mt. 
Sinai ePRO application per a data transfer agreement with the data processing center and Mt. Sinai 
to assure no PHI is transferred. Upon termination of the grant, all data and in an agreed format (SAS, 
ASCII) will be electronically transferred by ACI Clinical to AGA via the secure website.  
9.3 Training 
Each site will receive training on the data collection procedures and entry of data into the electronic 
registry. Each site will need to provide documentation of receiving and passing a training course in 
human subject’s protections.  
9.4 Records Retention 
In accordance with federal law all records will be kept for a minimum of three years after the study 
has closed.  
10 Ethics/Protection of Human Subjects 
10.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the principles set 
forth in The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects 
of Research, as drafted by the US National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research (April 18, 1979) and codified in 45 CFR Part 46 and/or the ICH 
E6; 62 Federal Regulations 25691 (1997).  
10.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials and all participant materials will be 
submitted for IRB 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 IRB 
review and approval before the changes are implemented in the study.  
10.3 Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the 
study and continues throughout study participation. Extensive discussion of risks and possible 
benefits of study participation will be provided to participants and their families, if applicable. A 
consent form describing in detail the study procedures and risks will be given to the participant. 
Consent forms will be IRB-approved, and the participant is required to read and review the 

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document or have the document read to him or her. The investigator or designee will explain the 
research study to the participant and answer any questions that may arise. The participant will sign 
the informed consent document prior to any study-related assessments or procedures. Participants 
will be given the opportunity to discuss the study with their surrogates or think about it prior to 
agreeing to participate. They may withdraw consent at any time throughout the course of the study. 
A copy of the signed informed consent document will be given to participants for their records. The 
rights and welfare of the participants will be protected by emphasizing to them that the quality of 
their clinical care will not be adversely affected if they decline to participate in this study.  
Minors may participate in the FMT registry. The minors and their legal guardians will undergo the 
consent process. Written consent must be provided by at least one guardian and, to the best of their 
ability, assent will be obtained from the minor.  
The consent process will be documented in the clinical or research record.  
10.4 Inclusion of Women, Minorities, and Children (Special Populations) 
Due to the complexity of state and federal requirements governing the participation of prisoners in 
research, prisoner-patients shall not be approached for participation in the research registry. All 
other participants regardless of age, gender, race, or ethnicity will be approached to participate in 
this observational study. Due to the nature of observational research, AGA will monitor the 
progress of the study for gender and minority inclusion.  
Due to the research activities, data collection, being no greater than minimum risk, children will be 
asked to participate. Consent for participation will be given by the child and at least one legal 
guardian. If the child reaches legal age, the participant will be consented again at the next patient 
interaction. There are only limited case reports and small studies of children who have received 
FMT for recurrent CDI with and without underlying IBD.40,41 To date FMT appears both safe and 
effective in children with recurrent or refractory CDI. Although age-specific rates and patterns of 
disease associated with CDI in children is poorly characterized, there has been a marked increase in 
CDI-associated hospitalizations from 7.24 per 10,000 in 1997, to 12.8 in 200653. Another large 
database analysis revealed a median age of diagnosis was 4 years and found that the 7% had one or 
more underlying complex chronic condition. Even with advances in medical care over the past 
several decades, the mortality rate in children with CDI remains stable at 4%.54 The experience of 
FMT as a primary treatment for IBD is also quite limited with mixed results.55,56 Despite limited 
data, FMT remains a potential therapeutic option for children with FMT and IBD. Sites that enroll 
minors will provide appropriate informed consent and assent per IRB protocols. 
11 PUBLICATION POLICY 
 
The Data Access and Publications Committee will establish requirements for publication of 
abstracts and research papers derived from FMT Registry data (e.g., acknowledgment of the FMT 
Registry and R24 support).  

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12 References 
 
1. 
Backhed, F., et al., Host-bacterial mutualism in the human intestine. Science, 2005. 
307(5717): p. 1915-20. 
2. 
Guinane, C.M. and P.D. Cotter, Role of the gut microbiota in health and chronic gastrointestinal 
disease: understanding a hidden metabolic organ. Therap Adv Gastroenterol, 2013. 6(4): p. 
295-308. 
3. 
Hamilton, M.J., et al., High-throughput DNA sequence analysis reveals stable engraftment of 
gut microbiota following transplantation of previously frozen fecal bacteria. Gut Microbes, 
2013. 4(2): p. 125-35. 
4. 
Kassam, Z., et al., Fecal microbiota transplantation for Clostridium difficile infection: 
systematic review and meta-analysis. Am J Gastroenterol, 2013. 108(4): p. 500-8. 
5. 
van Nood, E., et al., Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl 
J Med, 2013. 368(5): p. 407-15. 
6. 
Ridaura, V.K., et al., Gut microbiota from twins discordant for obesity modulate metabolism 
in mice. Science, 2013. 341(6150): p. 1241214. 
7. 
Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic 
sequencing. Nature 2010;464:59-65. 
8. 
Lozupone CA, Knight R. Species divergence and the measurement of microbial diversity. 
FEMS Microbiol Rev 2008;32:557-78. 
9. 
Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science 
2001;292:1115-8. 
10. 
Kelsen JR, Wu GD. The gut microbiota, environment and diseases of modern society. Gut 
Microbes 2012;3:374-82. 
11. 
Baker M. Genomics: The search for association. Nature 2010;467:1135-8. 
12. 
Virgin HW, Todd JA. Metagenomics and personalized medicine. Cell 2011;147:44-56. 
13. 
Zhang F, Luo W, Shi Y, et al. Should we standardize the 1,700-year-old fecal microbiota 
transplantation? Am J Gastroenterol 2012;107:1755. 
14. 
Khoruts A, Dicksved J, Jansson JK, et al. Changes in the Composition of the Human Fecal 
Microbiome After Bacteriotherapy for Recurrent Clostridium difficile-associated Diarrhea. 
Journal of Clinical Gastroenterology 2010;44:354-360 10.1097/MCG.0b013e3181c87e02. 
15. 
Chang JY, Antonopoulos DA, Kalra A, et al. Decreased Diversity of the Fecal Microbiome in 
Recurrent Clostridium difficile Associated Diarrhea. Journal of Infectious Diseases 
2008;197:435-438. 
16. 
Sartor RB. Therapeutic correction of bacterial dysbiosis discovered by molecular techniques. 
Proceedings of the National Academy of Sciences 2008;105:16413-16414. 
17. 
Kassam Z, Lee CH, Yuan Y, et al. Fecal microbiota transplantation for Clostridium difficile 
infection: systematic review and meta-analysis. Am J Gastroenterol 2013;108:500-8. 
18. 
Moayyedi, P., Surette, M.G., Kim, P.T. et al, Fecal microbiota transplantation induces remission 
in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology. 
2015;149:102–10913.19. 
 
19. 
Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors 
increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 
2012;143:913-6 e7. 
20. 
El-Matary W, Simpson R, Ricketts-Burns N. Fecal microbiota transplantation: are we opening 
a can of worms? Gastroenterology 2012;143:e19; author reply e19-20. 

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21. 
Kelly CP. A 76-year-old man with recurrent Clostridium difficile-associated diarrhea: review 
of C. difficile infection. Jama 2009;301:954-62. 
22. 
Zilberberg MD, Shorr AF, Kollef MH. Increase in adult Clostridium difficile-related 
hospitalizations and case-fatality rate, United States, 2000-2005. Emerg Infect Dis 
2008;14:929-31. 
23. 
Claud EC, Zhang X, Petrof EO, et al. Developmentally regulated tumor necrosis factor-alpha 
induced nuclear factor-kappaB activation in intestinal epithelium. Am J Physiol Gastrointest 
Liver Physiol 2007;292:G1411-9. 
24. 
Yoshino T, Ichimura K, Mannami T, et al. Multiple organ mucosa-associated lymphoid tissue 
lymphomas often involve the intestine. Cancer 2001;91:346-53. 
25. 
Petrof EO, Claud EC, Gloor GB, et al. Microbial ecosystems therapeutics: a new paradigm in 
medicine? Benef Microbes 2013;4:53-65. 
26. 
Sammons JS, Localio R, Xiao R, et al. Clostridium difficile infection is associated with increased 
risk of death and prolonged hospitalization in children. Clin Infect Dis 2013;57:1-8. 
27. 
O'Hara AM, Shanahan F. Gut microbiota: mining for therapeutic potential. Clin Gastroenterol 
Hepatol 2007;5:274-84. 
28. 
O'Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO reports 2006;7:688-693. 
29. 
McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases 
of recurrent Clostridium difficile disease. Am J Gastroenterol 2002;97:1769-75. 
30. 
Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile 
infection in adults: 2010 update by the Society for Healthcare Epidemiology of America 
(SHEA) and the Infectious Diseases Society of America (IDSA). infection control and hospital 
epidemiology 2010;31:431-455. 
31. 
Borody TJ, Warren EF, Leis SM, et al. Bacteriotherapy using fecal flora: toying with human 
motions. J Clin Gastroenterol 2004;38:475-83. 
32. 
Blaser MJ. The Jeremiah Metzger Lecture: Global warming redux: the disappearing 
microbiota and epidemic obesity. Trans Am Clin Climatol Assoc 2012;123:230-8; discussion 
239-41. 
33. 
Aas J, Gessert CE, Bakken JS. Recurrent Clostridium difficile Colitis: Case Series Involving 18 
Patients Treated with Donor Stool Administered via a Nasogastric Tube. Clinical Infectious 
Diseases 2003;36:580-585. 
34. 
Yoon SS, Brandt LJ. Treatment of refractory/recurrent C. difficile-associated disease by 
donated stool transplanted via colonoscopy: a case series of 12 patients. J Clin Gastroenterol 
2010;44:562-6. 
35. 
Silverman MS, Davis I, Pillai DR. Success of self-administered home fecal transplantation for 
chronic Clostridium difficile infection. Clin Gastroenterol Hepatol 2010;8:471-3. 
36. 
Brandt LJ, Aroniadis OC, Mellow M, et al. Long-term follow-up of colonoscopic fecal 
microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol 
2012;107:1079-87. 
37. 
Kelly CR, de Leon L, Jasutkar N. Fecal microbiota transplantation for relapsing Clostridium 
difficile infection in 26 patients: methodology and results. J Clin Gastroenterol 2012;46:145-
9. 
38. 
Neemann K, Eichele D, Smith P, et al. Fecal microbiota transplantation for fulminant 
Clostridium difficile infection in an allogeneic stem cell transplant patient. Transplant 
Infectious Disease 2012;14:E161-E165. 
39. 
Russell G, Kaplan J, Ferraro M, et al. Fecal bacteriotherapy for relapsing Clostridium difficile 
infection in a child: a proposed treatment protocol. Pediatrics 2010;126:e239-42. 
40. 
Kahn SA, Young S, Rubin DT. Colonoscopic fecal microbiota transplant for recurrent 
Clostridium difficile infection in a child. Am J Gastroenterol 2012;107:1930-1. 

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41. 
Russell GH, Kaplan JL, Youngster I, et al. Fecal transplant for recurrent Clostridium difficile 
infection in children with and without inflammatory bowel disease. J Pediatr Gastroenterol 
Nutr 2014;58:588-92. 
43. 
van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent 
Clostridium difficile. N Engl J Med 2013;368:407-15. 
44. 
Youngster I, Sauk J, Pindar C, et al. Fecal microbiota transplant for relapsing Clostridium 
difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, 
controlled pilot study. Clin Infect Dis 2014;58:1515-22. 
45. 
Dupont HL. Diagnosis and Management of Clostridium difficile Infection. Clin Gastroenterol 
Hepatol 2013;11:1216-23. 
46. 
Hecht GA, Blaser MJ, Gordon J, et al. What Is the Value of a Food and Drug Administration 
Investigational New Drug for Fecal Microbiota Transplantation in Clostridium difficile 
Infection? Clin Gastroenterol Hepatol 2013. 
47. 
Food and Drug Administration. Guidance for Industry: Enforcement Policy Regarding 
Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to 
Treat Clostridium difficile Infection Not Responsive to Standard Therapies, 2013. 
48. 
Bakken JS, Borody T, Brandt LJ, et al. Treating Clostridium difficile infection with fecal 
microbiota transplantation. Clin Gastroenterol Hepatol 2011;9:1044-9. 
49. 
Kelly CR, Kunde SS, Khoruts A. Guidance on preparing an investigational new drug application 
for fecal microbiota transplantation studies. Clin Gastroenterol Hepatol 2014;12:283-8. 
50. 
Moore T, Rodriguez A, Bakken JS. Fecal Microbiota Transplantation: A Practical Update for 
the Infectious Disease Specialist. Clinical Infectious Diseases 2014;58:541-545. 
51. 
Registries for Evaluating Patient Outcomes: A User’s Guide. In: Gliklich RE DN, ed. Rockville, 
MD: AHRQ, 2010. 
52. 
Tang WH, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine 
and cardiovascular risk. N Engl J Med 2013;368:1575-84. 
53. 
Zilberberg MD, Tillotson GS, McDonald LC. Clostridium difficile Infections among 
Hospitalized Children, United.  2010. 
54 
Kim J, Smathers SA, Prasad P, et al. Epidemiological features of Clostridium difficile-
associated disease among inpatients at children's hospitals in the United States, 2001–2006. 
Pediatrics 2008;122:1266-1270. 
55. 
Vandenplas Y, Veereman G, van der Werff Ten Bosch J, et al. Fecal Microbial Transplantation 
in a One-Year-Old Girl with Early Onset Colitis - Caution Advised. J Pediatr Gastroenterol Nutr 
2014. 
56. 
Kunde S, Pham A, Bonczyk S, et al. Safety, tolerability, and clinical response after fecal 
transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol 
Nutr 2013;56:597-601. 
 
 

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Supplement 1.  Donor/Recipient Screening and FMT Technique Data 
Elements (characteristics to be collected once at initiation of site) 
A. Transplant material 
• 
Donor Stool (full spectrum) 
▪ 
Fresh 
• 
Time from donation to delivery 
▪ 
Frozen 
• 
Time from donation to freezing 
o Source 
▪ 
Directed donor (known to recipient) 
• 
Related  
o Household versus non-household 
• 
Unrelated 
o Household versus non-household 
▪ 
Volunteer donor 
o Age-matched : yes, no, or unknown 
o Gender-matched: yes, no, or unknown  
• 
Modified human stool (filtered/processed and/or enhanced) 
o OpenBiome 
▪ 
 Batch/Lot number 
o Other stool bank 
o  
Specify bank 
o  
Batch/Lot number 
• 
 “Commercial” stool product 
o e.g. RBX2660, SER-109 
▪ 
Batch/Lot number 
o Other 
• 
Cultured bacterial product derived from stool 
o e.g. RePOOPulate 
• 
Microbial consortia not derived from stool 
B. Donor Screening (check all that apply) 
• 
Donor Selection 
o Donor screening Questionnaire (see Supplement 2) 
▪ 
AABB DHQ or AABB DHQ modified/derived 
▪ 
Other 
o Donor interview 
▪ 
Physician 
▪ 
Nurse Practitioner 
▪ 
Physician Assistant 
▪ 
Nurse 
▪ 
Research coordinator or assistant 
o Donor physical examination 
▪ 
Physician 
▪ 
Nurse 
▪ 
Research coordinator or assistant 
▪ 
Research Nurse 
• 
Laboratory  

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o No laboratory screening done 
o Screening laboratories unknown (FMT product) 
o Stool 
▪ 
Clostridium difficile toxin by PCR 
▪ 
C. difficile toxin EIA 
▪ 
C. difficile culture (anaerobic culture for toxigenic C. difficile) 
▪ 
Direct stool cytotoxin with tissue culture 
▪ 
C. difficile by glutamate dehydrogenase (GDH) testing  
▪ 
Routine bacterial culture for enteric pathogens (E coli, Salmonella, Shigella, 
Yersinia, Campylobacter) 
▪ 
Culture for Listeria monocytogenes  
▪ 
Culture for Vibrio (parahaemolyticus and cholerae) 
▪ 
Fecal Giardia antigen or DFA 
▪ 
Fecal Cryptosporidium antigen or DFA 
▪ 
Acid-fast stain for Cyclospora and Isospora  
▪ 
Trichrome Ova and parasites exam (O&P) 
▪ 
Rotavirus via EIA  
▪ 
Norovirus PCR 
▪ 
VRE culture 
▪ 
MRSA 
▪ 
New Delhi-Metallo-beta-lactamase-1 (NDM-1) 
▪ 
Carbapenem-resistant Enterobacteriaceae 
▪ 
Helicobacter pylori fecal antigen 
▪ 
Adenovirus EIA 
▪ 
Fecal calprotectin 
▪ 
Fecal lactoferrin  
▪ 
Luminex xTAG® Gastrointestinal Pathogen Panel (xTAG GPP) 
▪ 
BioCode GI panel 
▪ 
RIDA®GENE Bacterial Stool Panel 
▪ 
FilmArray® GI Panel 
▪ 
Other_____ 
o Serology 
▪ 
Norovirus 
▪ 
Helicobacter pylori serology (IgG, IgM or IgA) 
▪ 
JC Virus Ab 
▪ 
Strongyloides stercoralis Ab (IgG) 
▪ 
Schistosoma Ab (IgG) 
▪ 
Entamoeba histolytica Ab (IgG) 
▪ 
HIV, type 1 and 2 (Ab) 
▪ 
HIV, type 1 & 2 (qualitative PCR) 
▪ 
HIV p24 Ag test 
▪ 
HAV total Ab 
▪ 
HAV IgM 
▪ 
HBsAg 
▪ 
HBsAb 
▪ 
anti-HBc (IgG and IgM) 
▪ 
HCV Ab 
▪ 
RPR 
▪ 
Syphilis (TP) Ab test 
▪ 
FTA-ABS 

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▪ 
EBV Ab panel 
▪ 
EBV PCR 
▪ 
CMV IgG 
▪ 
CMV PCR 
▪ 
HSV 1 & 2 IgG 
▪ 
Human T cell lymphoma virus 1 & 2 
▪ 
Trypanosoma antibody 
▪ 
Other_____ 
C. Recipient Screening  
• 
Site specific exclusion criteria (check if site protocol excludes patients with any of the 
following) 
o Age <__ 
o Age >__ 
o BMI 
o Medical conditions 
▪ 
List conditions 
o Pregnancy/lactation 
o Recent or ongoing antibiotic use 
o Allergy  
o Malignancy 
o Immunosuppression 
o Other___ 
• 
Laboratory (baseline screening of recipient)-check any which apply 
o HIV 1 & 2 
o Hepatitis A  
o Hepatitis B surface Ag 
o Hepatitis B surface Ab  
o Hepatitis B core Ab 
o Hepatitis C Ab 
o RPR 
o Other 
   D. Transplant material preparation 
• 
Location of material preparation 
o Laboratory (research) 
o Laboratory (clinical) 
o Endoscopy unit 
o Pharmacy 
o Clinic/office 
o Other Patient care area (hospital room, infusion center) 
• 
Approximate weight (grams) or volume (mL) of stool used in preparation 
• 
Diluents 
o None/NA 
o Water  
▪ 
Volume___ 
o Saline 
▪ 
Volume___ 
o Glycerol 
▪ 
Percent___ 
o Other 

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• 
Processing 
o Blender 
▪ 
Household 
▪ 
Commercial 
▪ 
Laboratory mixer 
o Manual mixing 
• 
Filtration 
o None 
o Coffee filter 
o Medical gauze 
o Metal/disposable sieve 
o Laboratory microfilter 
• 
Material Storage 
o Stool 
▪ 
Fresh (used within ____hours of passage) 
▪ 
Frozen stool (used within ____months) 
• 
-20°C 
• 
≤-70°C 
o Other material (specify Openbiome, SER-109, RBX2660, etc.) 
▪ 
Room temperature 
▪ 
Refrigerated 
▪ 
Frozen 
• 
Amount of material delivered 
o Volume (ml) 
o Number of capsules 
o Contents/dose (CFU) if non-stool product 
E. Method of delivery 
• 
Oral ingestion: capsule 
o Fresh capsule 
o Frozen capsule 
o Lyophilized capsule 
o Number of capsules used 
• 
Oral ingestion: liquid 
• 
Nasogastric tube 
• 
Naso-intestinal tube 
• 
Upper endoscopy 
• 
Sigmoidoscopy 
• 
Colonoscopy 
• 
Enema 
F. Delivery schedule 
▪ 
Single dose delivery/ingestion 
▪ 
Multiple dose  
• 
Number of doses____ 
• 
Dosing Schedule 
o Daily  
o Weekly  
o Monthly  
▪ 
Maintenance (chronic therapy) 
• 
Schedule 

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Supplement 2. FMT Donor Questionnaire Data Elements 
 
Are you: 
1. Feeling healthy and well today?  
Yes  
No 
2. Currently taking any medication for infection?  
Yes  
No 
 
Have you: 
3. Taken any antibiotics within the past 6 months?  
Yes  
No 
4. Had any fevers, vomiting, diarrhea or other symptoms of infection within the past 4 weeks?  
 
Yes  
No 
In the past 8 weeks have you 
5. Had any vaccinations or other shots?  
Yes 
No 
6. Had contact with someone who has had the Smallpox vaccine? 
Yes  
No  
 
In the past 12 months have you: 
7. Had a blood transfusion?  
Yes  
No 
8. Had a transplant (organ, tissue, bone marrow, dura mater- brain covering)?  
Yes  
No 
9. Had a skin or bone graft?  
Yes  
No 
10. Come into contact with someone else’s blood?  
Yes  
No 
11. Had an accidental needle stick?  
Yes  
No 
12. Had sexual contact with anyone who has HIV/AIDS?  
Yes  
No 
13. Had sexual contact with a prostitute or anyone else who takes money or drugs as payment for 
sex?  
Yes  
No 
14. Had sexual contact with anyone who has ever used needles to take drugs or steroids, or 
anything NOT prescribed by their doctor?  
Yes  
No 
15. Had sexual contact with anyone who has hemophilia or has used clotting factor concentrates? 
 
Yes  
No  
16. Female donors: Had sexual contact with a male who has ever had sexual contact with another 
male (male donors circle “I am male)?  
Yes  
No  
 
I am male 
17. Had sexual contact with a person who has hepatitis?  
Yes  
No 
18. Lived with a person who has hepatitis?  
Yes  
No 
19. Had a tattoo?  
Yes  
No 
20. Had an ear or body piercing?  
Yes  
No 
21. Been treated for syphilis or gonorrhea?  
Yes  
No 
22. Been in lockup, jail or prison for >72 hours?  
Yes  
No 
 
In the past three years have you 
23. Been outside the United States or Canada?  
Yes  
No 
List location/time spent:_______________________ 
From 1980 through 1996, 
24. Did you spend time that adds up to three (3) months or more in the United Kingdom? Yes  
No 

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25. Were you a member of the U.S. military, a civilian military employee or a dependent member of 
the U.S. military?  
Yes  
No 
From 1980 to the present, 
26. Did you spend time that adds up to five (5) or more years in Europe? 
Yes 
No  
27.. Receive a blood transfusion in the United Kingdom or France?  
Yes  
No 
From 1977 to the present, have you 
28. Received money, drugs, or other payment for sex?  
Yes  
No 
29. Male donors: had sexual contact with another male, even once (female donors circle “I am 
female”)?  
Yes  
No 
 
I am female 
Have you EVER 
30. tested positive for HIV/AIDS virus?  
Yes  
No 
31. used needles to take drugs or steroids or anything NOT prescribed by your doctor? Yes  
No 
32. used clotting factor concentrates?  
Yes  
No 
33. had viral hepatitis?  
Yes  
No 
34. had any type of cancer (including leukemia)?  
Yes  
No 
35. had sexual contact with anyone who was born or lived in Africa?  
Yes  
No 
36. been in Africa?  
Yes  
No 
37. had sex for drugs or money?  
Yes  
No 
38. had any of the following gastrointestinal diseasesor problems? 
a. Irritable bowel syndrome?  
Yes  
No 
b. Crohn’s disease?  
Yes  
No 
c. Ulcerative Colitis?  
Yes  
No 
d. Chronic diarrhea?  
Yes  
No 
e. Gastrointestinal cancers?  
Yes  
No 
f. 
Celiac disease?  
Yes  
No 
39. received growth hormone made from human Pituitary glands?  
Yes  
No 
40. Have any of your relatives had Creutzfeldt-Jakob disease?  
Yes  
No 
 
General Medical History 
41. Do you have any autoimmune diseases (for example: Rheumatoid arthritis, Multiple Sclerosis, 
Lupus)  
Yes  
No 
If yes, please list:_________________________ 
42. Do you have any neurologic diseases (for example: Parkinson’s, Autism, ALS)?  
Yes  
No 
If yes, please list: _________________________ 
 

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Supplement 3. FMT Treatment Indications and Baseline 
Donor/Recipient Characteristics  
 
A. FMT Indication 
• 
C. difficile 
o Refractory 
o Recurrent 
o Severe 
• 
Inflammatory Bowel Disease 
o Ulcerative colitis 
o Crohn’s disease 
o IBD-U 
o Pouchitis 
• 
Irritable bowel syndrome 
o IBS-D 
o IBS-C 
o IBS-M 
o Other functional disorder 
• 
Chronic constipation 
• 
Obesity 
• 
Diabetes 
• 
Metabolic syndrome 
• 
NAFLD/NASH 
• 
Neurologic or Neurodevelopmental disorder 
• 
Other 
B. Baseline Characteristics 
• 
Donor (if known) 
o Age 
o Race/Ethnicity 
o Gender 
o Height 
o Weight 
o Donor medical conditions (check any which apply) 
▪ 
No significant medical or surgical history  
▪ 
BMI ≥30 
▪ 
Hypertension 
▪ 
Hyperlipidemia 
▪ 
Diabetes type II 
▪ 
Depression/anxiety 
▪ 
CAD 
▪ 
Cerebrovascular disease 
▪ 
Asthma 
▪ 
Other____ 
 
• 
Recipient characteristics (baseline) 
o Age 
o Race/Ethnicity 
o Gender 

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o Height 
o Weight 
o Medical co-morbidities 
▪ 
Metabolic (hypertension, diabetes II, hyperlipidemia) 
▪ 
Autoimmune (hypothyroid, RA, SLE) 
▪ 
Asthma/Allergic-Atopic conditions 
▪ 
Cardiovascular 
▪ 
Neurological conditions (MS, Parkinson, Alzheimer’s, autism) 
▪ 
Psychological (depression, anxiety, eating disorder) 
▪ 
IBS 
▪ 
IBD 
▪ 
Immunocompromised from medical condition or medication 
▪ 
Other 
o Labs (glucose, cholesterol, HDL, LDL, triglycerides, ALT, alkaline phosphatase, 
bilirubin, albumin, BUN, creatinine) 
• 
CDI baseline characteristics  
• 
Disease characteristics (pre-FMT) 
o Mild illness (recurrent) 
o Moderate (more severe but uncomplicated disease) 
o Severe  
o Severe complicated  
• 
Duration of C. difficile infection (weeks between initial diagnosis and FMT) 
• 
Number of CDI episodes 
• 
C. difficile strain  
o Nap-1 
o Non Nap-A 
o Unknown 
• 
Other treatments courses received (and number of courses of each, if known) for CDI 
prior to FMT  
o Metronidazole 
o Vancomycyin 
o Vancomycin taper/pulse dose 
o Fidaxomicin  
o Nitazoxanide 
o Rifaximin 
o IVIG 
o Saccharomyces. boulardii 
o Lactobacillus GG 
o Other probiotic 
o Other___ 
• 
Immediate Pre-FMT treatment(s) 
o Antisecretory therapy? 
▪ 
No 
▪ 
Yes 
• 
H2 blocker 
• 
Proton Pump inhibotor 
o Probiotics? 
▪ 
No  
▪ 
Yes 

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• 
list 
o Antibiotics? 
▪ 
No 
▪ 
Yes 
• 
Metronidazole 
• 
Vancomycin 
• 
Other 
o If yes, were antibiotics stopped? (yes/no) 
o Number of days off antibiotics prior to FMT 
• 
IBD Baseline characteristics 
o Type of IBD 
▪ 
CD 
▪ 
UC 
▪ 
IBD-U 
▪ 
Pouchitis 
o Disease location/extent  
▪ 
Montreal classification for adults >18 y/o 
▪ 
Paris classification for children <18 y/o 
o IBD treatment pre-FMT 
▪ 
Antibiotics 
• 
IV 
• 
Oral 
▪ 
Probiotics 
▪ 
Diet 
• 
Type of diet 
▪ 
Mesalamine 
• 
Oral 
• 
Rectal 
▪ 
Thiopurines 
▪ 
Methotrexate 
▪ 
Steroids 
• 
Oral 
• 
Rectal  
• 
IV 
▪ 
Biologics 
• 
Anti-TNF 
• 
Anti-Integrin 
• 
Ustekinumab 
• 
Other 
▪ 
Cyclosporin or tacrolimus 
▪ 
Other 
o IBD history 
▪ 
Number of years since initial diagnosis 
▪ 
Bowel surgery (ever) 
▪ 
IBD-related hospitalizations (within 12 months prior to FMT) 
o Severity of IBD at time of FMT (quiescent, mild, moderate, severe) 
o Disease activity scores (if available) 

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Supplement 4. FMT Effectiveness Outcomes 
A. Clostridium Difficile Infection 
• 
Post-FMT treatment(s) 
o Probiotics? 
▪ 
No  
▪ 
Yes 
• 
list 
o Antibiotics? 
▪ 
No 
▪ 
Yes 
• 
Metronidazole 
• 
Vancomycin 
• 
Fidaxomicin 
• 
Other 
o Days post-FMT antibiotic stopped 
• 
Cure (Resolution of diarrhea without need for further anti-CDI therapy) 
o Cured with single FMT 
o Cured with >1 FMT 
• 
Failure/Recurrence 
o How recurrence was diagnosed 
▪ 
Symptoms only  
▪ 
Stool testing only 
▪ 
Symptoms and +stool testing (EIA) 
▪ 
Symptoms and + stool testing (PCR) 
o Time of recurrence (weeks post-FMT) 
• 
Antibiotics received post-FMT for treatment of other infections  
o Agent 
o Indication 
o Months post-FMT 
B. Inflammatory Bowel Disease  
o IBD severity at time point post-FMT 
▪ 
Quiescent, mild, moderate, severe 
▪ 
Disease activity scores (if available) 
o IBD related hospitalizations post-FMT 
o IBD surgeries post-FMT 
▪ 
Number of days or weeks post-FMT 
o IBD-related medications post-FMT 
▪ 
Antibiotics 
• 
IV 
• 
Oral 
▪ 
Probiotics 
▪ 
Diet 
• 
Type of diet 
▪ 
Mesalamine 
• 
Oral 
• 
Rectal 
▪ 
Thiopurines 
▪ 
Methotrexate 

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▪ 
Steroids 
• 
Oral 
• 
Rectal  
• 
IV 
▪ 
Biologics 
• 
Anti-TNF 
• 
Anti-Integrin 
• 
Other 
▪ 
Cyclosporin or tacrolimus 
▪ 
Other 
o Other complications 
▪ 
Reclassification of disease type 
▪ 
Change in disease distribution 
▪ 
Abscess 
▪ 
Fistula  
▪ 
Perforation 
 

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Supplement 5. FMT Short-term Adverse Outcomes (within 30 days)  
 
• 
Procedure-related 
o Sedation complication 
o Bleeding 
o Perforation 
o Other 
 
• 
Symptoms post-FMT (within 30 days) 
o Diarrhea 
o Constipation 
o Nausea and/or vomiting 
o Bloating 
o Abdominal pain 
o Fever 
o Headache 
o Rash 
o Weight gain or loss 
o Other___ 
 
• 
Surgeries or other Procedures 
o Describe 
• 
Documented Infection (any) 
o Specify site/organism 
o FMT related (related, possibly related, unrelated) 
 
• 
Hospitalization 
o Reason for hospitalization 
o FMT related (related, possibly related, unrelated) 
 
• 
Life-threatening experience 
o Describe/diagnosis 
o FMT related (related, possibly related, unrelated) 
 
• 
Death 
o Cause of death 
o FMT related (related, possibly related, unrelated) 
o Site of death 
▪ 
Hospital 
▪ 
Home 
▪ 
Convalescent or skilled nursing facility 
 

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Supplement 6. FMT Long-term Adverse Outcomes (up to 2 years by 
physician report and 10 years by patient report)  
 
• 
Characteristics 
o Height 
o Weight 
• 
Serious Infection (HIV, viral hepatitis, prion, etc) 
• Use of new drugs 
o Describe 
• Surgeries or other Procedures 
o Describe 
• 
Diagnosis of any new condition 
o Autoimmune (hypothyroid, ITP, RA, SLE, MS, celiac, Type I diabetes, Sjogrens) 
o Asthma 
o Allergy/atopy 
o Metabolic disease 
▪ 
Diabetes II  
▪ 
Obesity 
o Psychiatric disorder 
o Neurologic disease 
▪ 
Parkinson’s disease 
▪ 
Amyotrophic lateral sclerosis (ALS) 
▪ 
Autism spectrum diagnosis 
o Cardiovascular disease 
▪ 
Myocardial infarction 
▪ 
Coronary artery revascularization 
▪ 
Cerebrovascular accident 
▪ 
Hypertension 
o Colon cancer 
o Other malignancy 
o Inflammatory bowel disease 
▪ 
Crohn’s  
▪ 
Ulcerative colitis 
▪ 
IBD-U 
o IBS 
▪ 
IBS-C 
▪ 
IBS-D 
▪ 
IBS-M 
o Other 
• 
 Hospitalization 
o Reason for hospitalization 
o FMT related (related, possibly related, unrelated) 
• 
Life-threatening illness 
o Describe/diagnosis 
o FMT related (related, possibly related, unrelated) 
• 
Death 
o Cause of death 
o FMT related (related, possibly related, unrelated) 

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APPENDIX A: Biorepository Sub-Study Protocol 
Title: Fecal Microbiota Transplant National Registry Biorepository  
 
Principal Investigator: Rob Knight, PhD, Professor, Departments of Pediatrics and Computer 
Science & Engineering, University of California San Diego 
1. 
Facilities  
Samples will be received and stored at the Knight Lab BRF2 Room 1220D, Bay D on the University 
of California San Diego Medical School campus. The American Gastrointestinal Association’s (AGA) 
administrative offices (Sonya Serra, 4930 Del Ray Ave, Bethesda, MD 20814) will track a 
deidentified list of participants in the FMT National Registry and the American Gut Project (AGP) 
barcodes assigned to those who consent to be part of the Biorepository. 
2. 
Estimated Duration of the Study 
10 years 
3. 
Specific Aims 
By collecting and characterizing the microbiomes of these samples, we aim to expand knowledge to 
help optimize practice in the transplantation of fecal microbiota or other gut‐related microbiota 
products. Specific aims characterizing the FMT National Registry-AGP biobank partnership include 
assessing the short and long-term safety of FMT and other gut-related microbiota products, to 
characterize the effectiveness of FMT and other gut-related microbiota products, and to gather 
information and promote scientific investigation on the practice in North America. 
4. 
Background and Significance  
The gut microbiome functions in a symbiotic relationship with the human body at a level of 
complexity akin to an organ or tissue. Recent advancements in genome sequencing technology have 
been used to identify the tremendous diversity of these microorganisms, opening a new frontier for 
research into the role of the gut microbiome in health and disease. It is now well appreciated that 
intestinal microbiota constitute a microbial “organ” that is integral to overall host physiology, 
including pivotal roles in metabolism and immune system function. Initial investigations have 
demonstrated that alterations in the gut microbiome (dysbiosis) may play a role in a number of 
gastrointestinal and non‐gastrointestinal disorders (e.g., Clostridium difficile infection (CDI), 
inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), nonalcoholic fatty liver disease, 
obesity, diabetes, metabolic syndrome, cardiovascular disease, cancer, and many others). 
 
The first clinical therapeutic application of this knowledge has been the use of fecal microbiota 
transplantation (FMT) to treat CDI. FMT involves administration of fecal material (containing 
intestinal microbiota) from a healthy individual (donor) to treat dysbiosis and restore beneficial 
intestinal flora and phylogenic diversity. FMT, which transfers highly complex microbial 

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communities, has proven to be beneficial in the treatment of recurrent CDI in numerous case series 
and a recently published randomized controlled trial. Because of recent trends in the incidence and 
severity of CDI and the growing body of literature, including current treatment guidelines, which 
support FMT, the number of physicians who perform FMT in the United States is growing. There are 
ongoing efforts to refine the process of FMT, with stool banks to supply carefully screened donor 
material and commercially available encapsulated formulations. Furthermore, investigations of 
FMT for the treatment of other conditions, such as IBD, are underway. 
 
A biorepository will facilitate analysis of stool specimens and linkage of these analyses to clinical 
data from the FMT National Registry, thereby allowing assessment of the association of clinical 
effectiveness and safety outcomes with the biological characteristics of stool specimens or other gut 
microbiota-based products. 
 
 
5. 
Research Design and Method  
This biorepository will prospectively enroll at least 1,000 patients who undergo fecal microbiota 
transplantation (FMT) at 75 sites throughout North America and their corresponding stool donors. 
All of these participants will first be enrolled in the FMT National Registry, administered by the 
AGA. Upon consenting to enroll in the registry, individuals will be given the opportunity to also 
enroll in this biorepository sub-study, after explanation of the biorepository and providing an 
additional signature on the registry informed consent. If individuals enroll in the biorepository, 
they will be provided an AGP sampling kit. The AGP barcode will be linked to the participant’s FMT 
registry code (which contains no personal health identifiers).  The stool samples will be mailed to 
the Knight Lab BRF2 Room 1220D, Bay D on the University of California San Diego Medical School 
campus. 
 
For patients enrolled in the biorepository sub-study, stool samples will be collected from the 
recipients before FMT and at 1 month after FMT. For stool donors enrolled in the biobank, samples 
will be collected from the stool they have donated for FMT procedures. The Knight lab at University 
of California San Diego will perform microbiome data analysis in accordance with the methods of 
the American Gut Project which may include amplicon sequencing, metagenomics, metabolomics, 
and proteomics.  The clinical data obtained as part of the FMT National Registry can then be linked 
to the analysis performed on stool specimens for investigations related to the aims outlined above 
for the FMT National Registry.  The Knight lab will also house the biobank in BRF2 on the University 
of California San Diego Medical School campus. 
6. 
Human Subjects 
Participation in the Biorepository will be limited to individuals in the FMT National Registry; 
therefore, the same restrictions on participation apply as in the FMT National Registry Protocol. 

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7. 
Recruitment and Procedures Preparatory to Research 
At the time of consenting to participate in the FMT National Registry, individuals will be given the 
opportunity to also enroll in the biorepository, after explanation of the biorepository and providing 
written informed consent. Participation is entirely voluntary. 
8. 
Informed Consent 
Informed consent to the Biorepository will be obtained at the time of consent to the FMT National 
Registry. Minors may participate in the Biorepository. The minors and their legal guardians will 
undergo the consent process. Written consent must be provided by at least one guardian and, to the 
best of their ability, assent will be obtained from the minor. The signed Biorepository consent forms 
will be retained with the FMT National Registry consent forms. The consent process will be 
documented in the clinical or research record. 
 
9. 
Alternatives to Study Participation 
The study is entirely voluntary and the only alternative is not to participate.  Not participating will 
confer no disadvantage to the participant. 
10. Potential Risks 
There are no risks of physical harm associated with participation in the biorepository. Participation 
in the biorepository does involve the potential risk of breach of confidentiality and associated 
privacy of the participants. 
 
11. Risk Management Procedures and Adequacy of Resources 
The biorepository will not hold confidential data. The samples will all be de-identified. Linked 
clinical data will be held only in the FMT National Registry as described in the FMT National 
Registry protocol. 
12. Privacy and Confidentiality Considerations Including Data Access and 
Management 
The biorepository will not hold confidential data. The samples will all be de-identified. Linked 
clinical data will be held only in the FMT National Registry as described in the FMT National 
Registry protocol. 
13. Potential Benefits 
There is no expected direct health benefit immediately associated with a patient’s participation in 
the FMT National Registry or biorepository. The biorepository samples may provide a valuable 

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resource for future research into FMT and related gut-microbiota products.  
 
14. Risk/Benefits Ratio 
There is no significant risk and no direct benefit to the participant.  
15. Expense to Participate 
This is not a clinical treatment study and all costs associated with the care and treatment of patient 
receiving FMT and follow‐up will be paid by the patient or their insurance provider. No costs will be 
incurred by participants related to participation in the biorepository. 
16. Compensation for Participation 
No compensation. 
17. Privileges/Certifications/Licenses and Research Team Responsibilities 
PI: Rob Knight, PhD  
American Gut Project Manager: Embriette Hyde, PhD 
Project sample coordinator - Greg Humphrey, BS 
IRB consultants: Brent Erickson, BA and Gail Ackermann, DDS  
 
All individuals have completed CITI training and have collectively over a decade of experience in 
protecting patient privacy and information. 
18. Bibliography 
Hallmans, G., & Vaught, J. B. (2011). Best practices for establishing a biobank. Methods in 
Biobanking, 241-260. 
Vaught, J., & Lockhart, N. C. (2012). The evolution of biobanking best practices. Clinica Chimica Acta, 
413(19), 1569-1575. 
Vaught, J., Rogers, J., Myers, K., Lim, M. D., Lockhart, N., Moore, H., ... & Compton, C. (2011). An NCI 
perspective on creating sustainable biospecimen resources. Monographs-Journal of the National 
Cancer Institute, (42), 1.