Prospective, Open-label Trial to Evaluate Efficacy of Fecal Microbiota Transplantation for Treatment of Chronic Gastrointestinal Dysbiosis or Clearance of Antimicrobial Resistant Organism.
Phase: NA
Conditions: Dysbiosis, Antimicrobial Resistant Organism
Sponsor: Vancouver Island Health Authority

 
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Title 
Prospective, open-label trial to evaluate efficacy of fecal 
microbiota transplantation for treatment of chronic
gastrointestinal dysbiosis or clearance of antimicrobial
resistant organism.  
Protocol  
Version Date 
GID.FMT.1     
April 06, 2020 Version 8 

Protocol No GID.FMT.1   Version 8 
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Table of Contents 
 
1. Rationale and Background….. .............................................................................................4 
2. Study Objectives and Outcome Measures ............................................................................ 5 
4. The Design of the Trial ...................................................................................................... 7 
5. Inclusion/exclusion criteria for patients and donors .............................................................. 9 
6. Trial steering and the data safety and monitoring committee ............................................... 12 
7. Enrollment stopping rules ................................................................................................ 12 
8. Trial Organization ........................................................................................................... 12 
10. Reference ...................................................................................................................... 13 
 
 
 
 
 

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ABBREVIATIONS 
 
 
CD 
 
CDAI 
 
CDI 
Crohn's Disease 
 
Crohn's Disease Activity Index 
 
Clostridioides difficile infection 
DSMC 
Data Safety Monitoring Committee 
FMT 
Fecal Microbiota Transplantation 
IBD 
 
IBS 
 
IBS-SSS 
Inflammatory Bowel Disease 
 
Irritable Bowel Syndrome 
 
Irritable Bowel Syndrome Severity Scoring 
System 
LYO-FMT 
 
MC 
Lyophilized Fecal Microbiota Transplant 
 
Microscopic Colitis 
PROM 
Patient Reported Outcome Measure 
UC 
Ulcerative Colitis 
 

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Study Rationale and Background 
Fecal Microbiota Transplantation (FMT), which had been predominantly utilized by the 
veterinarians until late 1990’s has generated a significant interest for its potential use in various 
gastrointestinal, psychiatric, neurologic and metabolic disorders within the past few years.  Since 
2010, there has been an explosion of research, publications and media coverage related to the 
high efficacy range, 80 – 90% for treatment of recurrent Clostridioides (Clostridium) difficile 
infection (rCDI). The exact mechanisms of its success in curing CDI are yet to be discovered. 
However, growing evidence suggests that it likely is a synergistic interaction of metabolites,  
bacteriophages, glycoproteins and bacterial, fungal components of microbiome, which mediate 
the effects of FMT.  Metagenomic studies have shown that patients with rCDI lack protective 
and diverse colonic microbiome and remain in a state of chronic dysbiosis.  Following a 
successful FMT, the microbiome of a patient with rCDI resembles that of the donor’s and 
remains as such overtime. There is no precise and agreed definition of dysbiosis.  For the purpose 
of this study, dysbiosis is defined as perturbation of host-microbial interactions which results in 
compositional changes in the fecal microbiota as determined by clinical criteria of constellation 
of symptoms, including change in the bowel function (diarrhea, constipation or bloating) in 
which an alteration of the microbiota is either known based on molecular or culture-based 
profiling or suspected according to the history, which includes but is not limited to repeated or 
prolonged use of antibiotics or gastrointestinal infection.   
The cause of inflammatory bowel disease (IBD) is unknown but studies have shown that IBD is a 
chronic inflammatory disease with altered and decreased microbiota diversity of the 
gastrointestinal tract when compared to the healthy individuals.  Canada has the highest incidence 
of IBD in the world.  The annual total (direct and indirect) health costs is estimated to $2.8 billion 
or $11,900 per person per year.17 IBD includes Crohn's Disease (CD) and Ulcerative Colitis (UC). 
While these diseases are collectively referred as IBD, there are distinct differences - most notably 
the area of the intestinal tract affected and the extent of the inflammation. UC typically affects the 
colon; the disease usually starts at the anus and may progress upward, and may even involve the 
entire colon.  While in CD, the inflammation tends to occur in patches and may involve any area 
throughout the entire intestinal tract; however, it most often affects the terminal ileum of the small 
intestine. Inflammation due to UC involves only the inner intestinal mucosa, while the 
inflammation in CD disease can extend through the entire thickness of the bowel wall.   
The management of CD is challenging due to extra-intestinal manifestations and overlapping 
symptomology with other inflammatory disorders. Treatment typically targets symptom relief, but 
and patients' ability to tolerate therapy also plays a key role. UC is characterized by lifelong 
relapsing and remitting colorectal inflammation. The cause of UC is unknown, but is thought to 
result from an aberrant immune response to environmental factors in genetically predisposed 
individuals. Metagenomic studies have shown that both patients with UC and recurrent 
Clostridiodes difficile infection (rCDI) lack diversity and richness of their colonic microbiota and 
remain in a state of chronic dysbiosis. While current drug treatments and surgery to remove the 
colon and rectum can reduce symptoms, they are costly, associated with adverse effects, and do 
not promote the restoration of healthy gut bacteria. Recent studies have shown that fecal 
microbiota transplant (FMT) is effective in treating IBD.  Recent case series in CD and clinical 
trials in UC patients have shown FMT to be a potential therapy to induce and maintain clinical 
remission in subset of IBD patients.  

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Microscopic colitis (MC) is a chronic inflammatory disease of the colon as manifested by chronic, 
watery, non-bloody diarrhea. MC usually occurs in middle-aged individuals with a female 
preponderance. Currently, there are limited treatment options for MC; budesonide may be effective 
for short-term treatment of MC and can improve quality of life. However, up to 80% will 
experience symptomatic relapse following cessation of budesonide.  Routine maintenance 
treatment with budesonide is controversial as long-term treatment may increase the risk of steroid-
related side effects.   
 
IBS is characterized by chronic, relapsing abdominal discomfort and altered bowel movements – 
constipation, diarrhea or mixed (diarrhea and constipation). IBS affects approximately 15-20% of 
Canadians and its economic and social burden is estimated to be over $6.5 billion per year in 
healthcare costs, work productivity losses, and reduced quality of life (QoL). The etiology and 
pathophysiology of IBS are not yet established, but appear to be a complex interplay between the 
host and environment factors.  Currently, there are no evidence-based therapies available to cure 
IBS.  Studies have shown that fecal microbiota transplantation (FMT) may be an effective IBS 
treatment.  Given the lack of safe and effective treatment for IBD and IBS which are thought to be 
due to gastronintestinal dysbiosis, this study was conducted.   
 
There is also some  evidence in the literature showing efficacy of FMT in clearance of 
antimicrobial resistant organism (ARO) such as extended-spectrum of beta-lactamases (ESBLs), 
carbapenem resistant or vancomycin resistant enterococci from the gastrointestinal tract of 
colonized patients.11-13 There have been requests from clinicians to utlize FMT for eradication of 
ARO in rectally colonized patients admitted to an acute care facility in order to facilitate their 
discharge to a longterm care facility as they were otherwise eligible to be transferred.      
Study Objectives and Outcome Measures 
The objective of this study is to assess the efficacy of FMTs via enema for 1) symptom 
improvement in individuals with a formal diagnosis of dysbiosis due to active inflammatory bowel 
disease (CD, UC),  microscopic colitis or irritable bowel syndrome; 2) clearance of antimicrobial 
resistant organism from the gastrointestinal tract.  
 
Primary Outcome Measurements: 
For the participants with chronic GI dysbiosis, the efficacy of FMT treatment will be based on 
improvement in participant’s symptom score from baseline (pre-transplant) to intervention (post-
transplant) 4 weeks, 12 weeks and 1 year following FMT.  For participants with ARO colonization, 
determination of clearance of ARO based on stool culture for ARO at baseline, day 7, day 30 and 
3 months following last FMT.  
 
Secondary Outcome Measurements for participants with IBD, MC or IBS:   
1. Evaluate efficacy and safety of FMT in patients with chronic gastrointestinal dysbiosis 
and antimicrobial resistant organism in the gut 

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2. Evaluate the Ulcerative Colitis Disease Activity Index from baseline and following each 
FMT using partial-MAYO score.    
3. Evaluate Crohn’s Diseases Activity Index (CDAI) change from baseline 4 weeks, 12 
weeks and 1 year post-FMT. 
4. Evaluate Microscopic colitis response to FMT using physician’s global assessment and 
number of unformed bowel movements per 24 hours 
5. Evaluate Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) grade assessment 
change from baseline, 4 weeks, 12 weeks and 1 year post-FMT. 
 
Ulcerative Colitis  
The efficacy of FMT for UC will be determined based on changes to partial-MAYO score 
from baseline and at weeks 4, 12 and year 1, following the treatment.    Partial-MAYO is 
a validated scoring system to determine the activity of UC.  It uses the three non-invasive 
components of the full Mayo Score (stool frequency, rectal bleeding and Physician’s global 
assessment) as perceived by the patient, to score ulcerative colitis patient’s disease severity 
score. The index considers these three clinical parameters, each of which is assigned a score 
from 0 to 3 according to the clinical evaluation, with a total possible score of 9.  Higher the 
score, more severe the disease; score of 0 to 1 is considered in remission; 2 – 4 mild; 5 – 
7; moderate; > 7 severe colitis. 
 
Crohn’s Disease 
CDAI is a validated instrument used in adults with active Crohn’s disease. The index 
consists of eight factors, 2 of which are subjective: stool habits; pain; general well being; 
features of extra intestinal disease; use of opiates for diarrhea; abdominal mass; hematocrit 
(hct); and percentage of body weight below standard. Scores range from 0 to ~ 600: > 450 
is severe disease; 220 – 450 moderately active disease; 150 – 219 mildly active disease.  
Clinical remission is defined as a CDAI score <150, clinical response is either a CDAI 
score <150 or a CDAI reduction of ≥100 from baseline. 
 
Microscopic Colitis 
Physician’s global assessment and number of unformed bowel movements per 24 hours 
were employed to assess response to FMT as these parameters used to determine MC 
treatment in clinical trials and care.  
 
Irritable Bowel Syndrome 
The Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) is a validated 
instrument with a scoring system which produces  a  meaningful  value  that  is both 
reproducible  and  sensitive  to  change. The instrument contains five questions across the 
following domains: pain; distension; bowel score and quality of life. Each question can 
generate a maximum score of 100  using prompted  visual  analogue  scales; the maximum 
achievable score is 500.  IBS-SSS is mild for scores 75 – 175; moderate 176 – 300 and 
severe if > 300. 
 

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The Proposed Trial 
The proposed design of the study  
The design of this research is a prospective open-label trial using lyophilized or frozen FMT to 
evaluate efficacy of fecal microbiota transplantation for treatment of chronic gastrointestinal (GI) 
dysbiosis and clearance of antimicrobial resistant organism (ARO) from the GI tract of the ARO 
colonized individuals.  
The planned trial interventions 
 
Recruitment 
The research coordinator will be responsible for coordinating the recruitment, screening of 
potential participants using the inclusion/exclusion criteria and reviewing with the PI.  The PI 
will make the final determination of a potential participants’ eligibility. Fifty participants with 
chronic GI dysbiosis will be recruited. Twenty patients with confirmed ARO will be recruited to 
take part in this study; the ARO study results will be used to determine the feasibility of further 
study. 
 
Study Population 
 
The participants will consist of patients over the age of 18 years who or their legally authorized 
representative consent and comply with study procedures.  Participants will be required to have a 
formal diagnosis of chronic gastrointestinal dysbiosis by a referring gastroenterologist or known 
to be colonized with ARO based on positive rectal cultures for same organism on 2 separate 
occasions (each culture 1 month apart) and must have a positive culture within 14 days of 
enrollment.  
 
ARO Participants 
 
Following informed consent and prior to receiving FMT, enrolled ARO participants will have 
their blood collected for Hepatitis BsAg, Hepatitis C Ab, HIV, Syphilis serologies. Blood is 
collected for  these pathogens to determine their serostatus at the time of study enrollment. 
Participants are advised through the study consent that if their blood tests positive for any of 
these diseases, the researchers are required to notify the public health department and that the 
public health department may contact them. 
 
At baseline, ARO participants will have medical history, physical exam done by the physician-
researcher, and information on concomitant medications will be collected. The participants will 
receive a total of two lyophilized FMT (LYO-FMT) or frozen FMT enemas using stool samples 
collected from healthy, screened donor(s); the participant will receive the first FMT treatment 
week 1 and a second FMT will be administered within three weeks of first treatment.  Participant’s 
stool will be retested one week, one month and 3 months following the second FMT to determine 
whether the ARO has been eradicated. 

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GI Dysbiosis Participants 
 
Following informed consent and pre-transplant, enrolled participants will have their blood 
collected for Hepatitis BsAg, Hepatitis C Ab, HIV, Syphilis serologies unless these serologies 
were performed within 3 months of enrollment. Blood is collected for these pathogens to determine 
their serostatus at the time of study enrollment and prior to receiving FMT.  
All participants will be assessed at day 1 by the physician-investigator. A medical history and 
physical examination will be performed. In addition, optional blood and stool samples may be 
collected from IBD/IBS participants who consented for these samples prior to the FMT and at 
weeks 4, 12 and 6 months from FMT.   
The participants will receive lyophilized FMT (LYO-FMT) or frozen FMT enemas using stool 
collected from healthy, screened donor(s).  Participants with will receive FMT treatment via 
retention enema(s) twice weekly for 4 weeks. If there is symptom improvement after 4 weeks of 
treatment, then the participants will receive FMT treatment once weekly for 4 additional weeks.  
If the participant does not experience symptom improvement after the initial 4 weeks of 
treatment, the physician-investigator will discuss options with the participant and a mutual 
decision will be reached to pursue an additional 4 weeks of FMT treatment or withdraw from the 
study and pursue usual care. When continued improvement is seen then the participants will 
receive FMT maintenance; the frequency of FMT treatment is participant dependent and is at the 
discretion of the physician-investigator and is based upon clinical exam and symptomatic 
improvement. If no improvement is seen after the 8th FMT, then the participant will be 
withdrawn from the study and s/he reverts to usual care for his/her condition. Participants can opt 
to receive maintenance FMT in the clinic or be trained by study staff for home administration.  
At the time of each study visit and follow up, participants will be assessed for clinical response, 
including bowel movements and adverse reactions.  Any participant who reports worsening 
symptoms or AE/SAE will return to the clinic for assessment by the physician investigator. At 
that time, the participant will undergo a physical exam. Additional tests may be ordered (i.e 
blood work) at the discretion of the treating physician investigator.  
From the previous UC FMT trial, it was discovered that the participants who responded to the 
initial series of FMT, required ongoing maintenance FMT to remain UC symptom-free.  Following 
the completion of 6-month FMTs, participants will have the option of continuing with the 
maintenance FMT which can range from one FMT every 2 weeks to every 6 months depends on 
the individual.   In the event that it is not possible for the participant to return to the clinic or 
requires significant time/travel commitments to receive the FMTs, either the participant or a 
household member will be trained to store and to administer the lyophilized FMT at home, if the 
participant is willing to do so.  
The home maintenance FMT will be offered only when all the following conditions are met: 
1. 
There is clinical evidence of improvement following the initial FMT series. 
2. 
Participant agrees to continue with maintenance FMT 
3. 
Participant or a household can safely administer FMT at home as assessed by the research 
staff. 
4. 
There is availability of lyophilized FMT for distribution 

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5. 
The participant or delegate is willing to notify the research staff of the progress and 
request for lyophilized FMT to be available either by picking them up or be shipped 3 
weeks prior to needing additional lyophilized FMT.   
6. 
Participant agrees to pay for the shipping supplies and the  shipment of FMTS 
 
Inclusion/exclusion criteria for patients and donors  
 
Participant inclusion criteria 
 Age 18 years or older. 
 Able to provide informed consent.  
 Willing and able to comply with all the required study procedures. 
 Must have at least one of the following conditions 
o Underlying inflammatory bowel disease (ulcerative colitis, Crohn’s disease), or 
microscopic colitis diagnosed by a gastroenterologist 
o Irritable bowel syndrome as defined by Rome IV diagnostic criteria*: 
  Recurrent abdominal pain or discomfort** at least 3 days/month in last 3 
months associated with two or more of the following: 
 Improvement with defecation  
 Onset associated with a change in frequency of stool  
 Onset associated with a change in form (appearance) of stool 
* Criterion fulfilled for the last 3 months with symptom onset at least 6 
months prior to diagnosis  
** “Discomfort” means an uncomfortable sensation not described as 
pain. 
o Chronic severe constipations/dysbiosis as diagnosed by a gastroenterologist 
 Colonized with ARO based on positive rectal cultures for same organism on 2 separate 
occasions (each culture 1 month apart) and must have a positive culture within 14 days of 
enrollment.  
 
Particpant exclusion criteria 
 Planned or actively taking another investigational product 
 Patients with neutropenia with absolute neutrophil count <0.5 x 109/L 
 Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray 
 Peripheral white blood cell count > 30.0 x 109/L AND temperature > 38.0 ºC 
 Active gastroenteritis due to Salmonella, Shigella, shiga toxin-producing E. coli, Yersinia 
or Campylobacter. 
 Unable to tolerate FMT or enema for any reason. 
 Requiring systemic antibiotic therapy at the time of FMT. 
 Actively taking Saccharomyces boulardii or other probiotic; yogurt is allowed 
 Severe underlying disease such that the patient is not expected to survive for at least 30 
days. 
 History of severe allergy to any food 
 

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Donor inclusion  
 Able to provide and sign informed consent. 
 Able to complete and sign the donor questionnaire 
 Able to adhere to fecal transplantation stool collection standard operating procedure.   
 
Donor exclusion 
 Tested positive for any of the following: Human Immunodeficiency virus (HIV) 1/2, 
hepatitis IgM, hepatitis B (HBsAg), hepatitis C antibody, syphilis, human T- 
lymphotrophic virus (HTLV) 1/II and COVID-19 Detection of vancomycin resistant 
Enterococcus (VRE),  methicillin resistant S. aureus (MRSA), Extended-spectrum beta-
lactamase (ESBL) or carbapenem-resistant enterobacteriaceae (CRE); Salmonella, 
Shigella, shiga toxin-producing E.coli, Yersinia and Campylobacter, ova, parasites, C. 
difficile toxin, norovirus, adenovirus, rotavirus on stool examination 
 
Physical contact with COVID-19 positive individual within 14 days of stool donation 
 History of any type of active cancer or autoimmune disease  
 History of risk factors for acquisition of antibiotic resistant organisms (MRSA, VRE, 
ESBL, CRE) HIV, syphilis, Hepatitis B, Hepatitis C, prion or any neurological disease as 
determined by the donor questionnaire, appendix A.  
 History of gastrointestinal comorbidites, e.g., inflammatory bowel disease, irritable bowel 
syndrome, chronic constipation or diarrhea 
 Receipt of blood transfusion from a country other than Canada in preceding 6 months 
 Antibiotic use or any systemic immunosuppressive agents in the 3 months prior to stool 
donation 
 Receipt of any type of live vaccine within 3 months prior to stool donation 
  *(participant with history of severe allergy to any food is excluded)History of 
depression, anxiety or panic disorder 
 History of any type of active cancer or autoimmune disease  
 Body mass index > 29 
 Failed any one of the donor screening questionnaire at the time of donor screening 
 Any current or previous medical or psychosocial condition or behaviours which in the 
opinion of the investigator may pose risk to the recipients or the donor 
 
Adverse Event Reporting 
 
All adverse drug event (ADE) and serious adverse events (SAE) will be tracked in the 
participant’s study file and REDCap and reported to Island Health’s Clinical Research Ethics 
Board (CREB). As per Health Canada, a SAE is defined as “an adverse drug reaction that 
requires inpatient hospitalization or prolongation of existing hospitalization, that causes 
congenital malformation, that results in persistent or significant disability or incapacity, that is 
life threatening or that results in death”. Each SAE that is attributed to FMT is subject to 
expedited reporting to Health Canada and should be reported individually in accordance with the 
data element(s) specified in the Health Canada/ICH Guidance Document E2A: "Clinical Safety 
Data Management: Definitions and Standards for Expedited Reporting". Expedited reports are 
required for events that meet all of these three criteria:  serious, unexpected and a suspected 
causal relationship; this is defined as any untoward medical occurrence that at any dose results in 

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any one of the following: results in death; is life-threatening; requires inpatient hospitalization or 
prolongation of existing hospitalisation; results in persistent or significant disability/incapacity or 
is a congenital anomaly/birth defect. An event reaction causality scoring system will be used to 
determine the probability of the relationship of the event to study intervention. Source documents 
will be used to capture AEs and SAEs.  All AEs will be reported to the CREB within 24 hours of 
the PI being aware of the event.  
 
Known side effects of FMT are described in table 6.0; these potential effects are listed in the 
informed consent and participants are advised to report these and any other effects that they feel 
is relevant or causing concern. 
 
FMT Side Effects 
Possible FMT Side Effects 
Frequency that the side effect 
has been reported 
Hard stool 
10% 
Increase in flatulence or passing gas 
10% 
Stomach discomfort 
8% 
Increase appetite 
3% 
Nausea 
2% 
Minor temporary pressure or discomfort in the rectum 
1% 
There has been a report of transmission of multi-drug resistant organism (MDRO) to patients 
who received FMT from a donor, whose stool was not screened for the MDRO.   
There may be a small risk of transmission and infection due to MDRO.  However, the donor’s 
stool samples used at Vancouver Island Health Authority routinely undergo screening for 
MDRO.  The donor’s blood and stool are regularly tested for transmissible infectious organisms 
that may cause disease.  If a donor and/or their stool sample shows abnormal result(s), such stool 
samples will not be considered for FMT processing. 
 
Proposed sample size and the justification for the assumptions  
 
Fifty participants will be recruited for the chronic GI dysbiosis component of the study based on 
the 5% response in placebo group and 24% in FMT arm with significance level 5% and power of 
80% in the FMT trial of ulcerative colitis. For the ARO participants, the sample size will be 20 as 
this will be a pilot project to determine the feasibility of further study.  
 
The proposed type of statistical analyses 
The clinical response rate will be determined using standard binary outcome protocols. Also, 
logistic regression and survival analysis methods will be performed. The primary endpoints of 
clinical response, and treatment failure will be analyzed by logistical regression.  

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The proposed frequency of analyses 
The analyses will be conducted following the data collection stage at the end study.  An interim 
analysis will be performed after 15 patients have been recruited to assess safety and ongoing trial 
feasibility for the dysbiosis group.    
 
Trial steering and the data safety and monitoring committee 
An independent data monitoring committee (DMC) will be constituted prior to the conduct of the 
trial and this committee will continue to serve to oversee until the completion of the trial.  
 
The DSMC will convene on a periodic basis; normally, after data on the first 20% of participants 
have been enrolled into a study, and at the conclusion of enrollment.  The committee will be 
advised on a regular basis of participant enrollment; receive (verbatim) each report of a serious 
adverse event (SAE), with an investigator assessment of causality/attributability of at least 
possibly related to study that is provided from the investigator and follow-up SAE reports will be 
promptly forwarded to the Chair. 
 
Enrollment stopping rules 
If the DMC decided that there were a pattern consistent with an important increase in frequency 
of the occurrence of one or more types of SAEs then a review by the DMC Chair will be requested. 
The DMC, upon review of the participant-specific reported SAEs, will: Convene a meeting of the 
full DMC for the purpose of providing a recommendation to the investigator regarding cessation 
or continuation of enrollment in the study. Such recommendation will be formally provided within 
24 hours of such meeting and will not be influenced by actions or opinion of the any of the 
investigators; Recommend that enrollment in the study be halted if as many as three (3) participants 
that received treatment with FMT were reported to experience the same or substantially similar 
types of SAE and the DMC concluded that such SAEs could be reasonably related to treatment 
with FMT; Recommend that enrollment in the study be halted if any one participant who received 
treatment with FMT were reported to experience an SAE that had fatal or life-threatening outcome 
and the DMC concluded that such SAE could be reasonably related to FMT. 
 
Trial Organization 
Data Management, Treatment Allocation and Analysis Centre 
Vancouver Island Health Authority (VIHA) 
Royal Jubilee Hospital 
Trial Training 
Prior to patient recruitment, all research laboratory staff will be trained and provided with 
manufacturing of FMT suspension and the lyophilization and reconstitution for delivery of 
FMT by enema to patients.  Copies of delegation logs documenting site staff responsibilities 
and training dates will be retained at VIHA.  

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References 
1. 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.  
2. Lee Ch, Belanger JE, Kassam Z, et al.  The outcome and long-term follow-up of 94 
patients with recurrent and refractory Clostridium difficile infection using single to 
multiple fecal microbiota transplantation via retention enema.  Eur J Clin Microbiol 
Infect Dis 2014;33;1425-1428. 
3. Kassam Z, Lee CH, Yuan Y. et al.  Fecal microbiota transplantation for Clostridium 
difficile infection:  systematic review and meta-analysis.  Am J Gastroenterol 
2013;108:500-508. 
4. Song Y, Garg S, Girotra M, et al. Microbiota dynamics in patients treated with fecal 
microbiota transplantation for recurrent Clostridium difficile infection. Plos ONE 
2013;8:e81330.  
5. Hamilton M, Weingarden A, Unno T, Khoruts A, Sadowsky M. High-throughput DNA 
sequence analysis reveals stable engraftment of gut microbiota following transplantation 
of previously frozen fecal bacteria. Gut Microbes 2013;4:125–133.  
6. Weingarden A, Chen C, Bobr A, et al. Microbiota trans- plantation restores normal fecal 
bile acid composition in recurrent Clostridium difficile infection. Gastronint Liver Physiol 
2014;306:310–9.  
7. Borody TJ, Warren EF, Leis S. et al.  Treatment of ulcerative colitis using fecal 
bacteriotherapy.  J Clin Gastroenterol 2003;27:42-47. 
8. Moayyedi P, Surette MG, Kim PT, et al.  Fecal microbiota transplantation induces 
remission in patients with active ulcerative colitis in a randomized, controlled trial.  
Gastroenterology 2015; 149:102-109. 
9. Rossen NG, Fuentes S, van der Spek MJ, et al.  Findings from a randomized controlled 
trial of fecal transplantation for patients with ulcerative colitis.  Gastroenterology 
2015;149:110-118.   
10. http://thepowerofpoop.com/epatients/fecal-transplant-instructions/ 
11. Singh R, Nieuwdorp IJ, Berge JM, Bemelman FJ, Geerlings SE.  The potential beneficial 
role of faecal microbiota transplantation in diseases other than Clostridium difficile 
infection.  Clin Microbio Inf  2014;20:1119-1125. 
12. Lagier JC, Million M, Fournier PE, et. al.     Faecal microbiota transplantation for stool 
decolonization of OXA-48 carbapenemase-producing Kelbsiella pneumonia.  J Hosp 
Infect 2015;90:171-174. 
13. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-
safety-alert-regarding-use-fecal-microbiota-transplantation-and-risk-serious-adverse.