Optimal Fecal Microbiota Transplant Dosing for Mild to Moderate Ulcerative Colitis

Study Overview
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Brief Summary
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This is a prospective unblinded, randomized trial for the use of Fecal Microbiota Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or without antibiotic pretreatment.

Detailed Description
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This is a prospective open-label, randomized trial for the use of Fecal Microbiota Transplantation (FMT) for the treatment of Ulcerative Colitis (UC), in combination with or without antibiotic pretreatment. This trial involves 11 study visits at UCSF in San Francisco, CA. The routes of administration will be via colonoscopy for all subjects with maintenance therapy administered orally (i.e. using encapsulated FMT) for half of the subjects and per rectum by enema in the other half of the subjects. Additionally, the utility of pretreatment antibiotics will be assessed.

Official Title
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Optimal Fecal Microbiota Transplant Dosing for Mild to Moderate Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Biological: Fecal Microbiota Transplantation (FMT), OpenBiome
* Other: pretreatment antibiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with history of mild to moderate Ulcerative Colitis confirmed by endoscopy and pathology. Total Mayo score 4-9, endoscopic subscore ≥1; patients who have not had endoscopic evaluation within one year of enrollment will have flexible sigmoidoscopy for evaluation. Age 18 - 64 and deemed otherwise healthy at the discretion of the investigator. Concurrent therapies with mesalamine (stable x 4 weeks), immunomodulators (stable x 3 months), and biologic agents (stable x 3 months) will be allowed to continue during study. If patient is on prednisone, the dose must be ≤ 10mg/day at the time of treatment and will be weaned by 2.5mg/week during the study period. Exclusion Criteria: Severe or refractory UC defined as Mayo score ≥10, endoscopic disease activity score 3 Untreated enteric infection (positive stool test for any of the following: Clostridium difficile, Salmonella, Shigella, Yersinia, Campylobacter, enteropathogenic E. coli or other enteric infection at the discretion of the investigator. History of colectomy Disease limited to distal proctitis Patients taking probiotics within 6 weeks of planned FMT therapy. Severe immunodeficiency, inherited or acquired (e.g. HIV, chemotherapy or radiation therapy) Patients with the following laboratory abnormalities: absolute neutrophil count (ANC) < 1000 / µl, platelets <50 x 10^9 /L,, hemoglobin <6.5 g/dL.. History of anaphylaxis (severe allergic reaction) to food allergens (e.g. tree nuts, shellfish) Dysphagia (oropharyngeal, esophageal, functional, neuromuscular) History of recurrent aspiration episodes Documented severe gastroparesis Active intestinal obstruction Patients with renal insufficiency (GFR < 50ml/min) Allergy to the following generally regarded as safe ingredients (GRAS): glycerol, acid resistant HPMC, gellan gum, cocoa butter, titanium dioxide Adverse event attributable to any previous FMT Allergy/intolerance to proton pump inhibitor therapy Allergy/intolerance to vancomycin, metronidazole, or neomycin. Non-steroidal inflammatory medications (NSAIDs) as long-term treatment, defined as use for at least 4 days a week each month. Cholestyramine use Any condition in which the investigator thinks the FMT treatment may pose a health risk (e.g. severely immunocompromised) Simultaneous participation in another interventional clinical trial Patients who are pregnant, breast feeding or planning pregnancy during study trial period. During the trial period until one week after the trial end: Non-use of appropriate contraceptives in females of childbearing potential (e.g. condoms, intrauterine device (IUD), hormonal contraception, or other means considered adequate by the responsible investigator) or in males with a child-fathering potential (condoms, or other means considered adequate by the responsible investigator during treatment) or well-founded doubt about the patient's cooperation Patients with any other significant medical condition that could confound or interfere with evaluation of safety, tolerability or prevent compliance with the study protocol at the discretion of the investigator Life expectancy <6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>pretreatment antibiotics + FMT delivered by colonoscopy + FMT capsules per week x 6 weeks | Biological: Fecal Microbiota Transplantation (FMT), OpenBiome<br>* Delivered by colonoscopy, enema or orally (as capsules)<br>Other: pretreatment antibiotics<br>* 5 day course (vancomycin PO 500mg bid, metronidazole PO 500mg bid, and neomycin PO 500mg bid) starting 6 days prior FMT<br>* Other names: vancomycin, metronidazole, neomycin;|
| Experimental: 2<br>no antibiotics, FMT delivered by colonoscopy + FMT capsules per week x 6 weeks | Biological: Fecal Microbiota Transplantation (FMT), OpenBiome<br>* Delivered by colonoscopy, enema or orally (as capsules)<br>|
| Experimental: 3<br>pretreatment antibiotics + FMT delivered by colonoscopy + FMT delivered by enema once per week x 6 weeks | Biological: Fecal Microbiota Transplantation (FMT), OpenBiome<br>* Delivered by colonoscopy, enema or orally (as capsules)<br>Other: pretreatment antibiotics<br>* 5 day course (vancomycin PO 500mg bid, metronidazole PO 500mg bid, and neomycin PO 500mg bid) starting 6 days prior FMT<br>* Other names: vancomycin, metronidazole, neomycin;|
| Experimental: 4<br>no antibiotics, FMT delivered by colonoscopy + FMT delivered by enema once per week x 6 weeks | Biological: Fecal Microbiota Transplantation (FMT), OpenBiome<br>* Delivered by colonoscopy, enema or orally (as capsules)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of a Serious Adverse event (SAE), solicited and unsolicited AE, new gastrointestinal medical condition and diagnoses from FMT treatment or new infection from FMT treatment | safety endpoint | up to 1 year | 
| Steroid-free Clinical Remission at week 9 + endoscopic remission or response defined as total Mayo score ≤ 2 with all four sub-scores ≤ 1 and a ≥ 1 point reduction in endoscopy sub-score |  | 8 weeks post initial treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in microbiome with FMT therapy. Changes in the microbiome: assessed by frequent stool sampling for 16S rRNA analysis prior to each FMT therapy and after the last capsule/enema dose |  | up to 1 year | 
| Clinical Response: decrease in Mayo score by ≥ 3 points, decrease in bleeding subscore by ≥ 1, or absolute subscore of 0-1 |  | 8 weeks post initial treatment | 
| Progression of disease defined by initiation of anti-TNF agents or Corticosteroids: Initiation of anti-TNF agents (such as infliximab, adalimumab, certolizumab, vedolizumab and steroids). Includes time gap until additional agents are started. |  | 2, 4 and 8 weeks post initial FMT | 
| Progression of disease defined by increase in dosages of current UC medications |  | 2, 4 and 8 weeks post initial FMT | 
| Progression of disease defined by time to colectomy |  | up to one year post initial FMT | 
| Time to death secondary to UC |  | up to one year post initial FMT | 
| Progression of disease defined by clinical flare (Time to next flare) |  | 2, 4 and 8 weeks post initial FMT | 
| Increase in Quality of Life (based on RAND SF-36 survey and score) |  | 8 weeks post initial FMT | 
| Changes in Mood/Depression Score (based on PHQ-9 survey and score) |  | 8 weeks post initial FMT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative colitis, FMT, fecal transplant