LFMT vs Placebo in New Biologic Start for Ulcerative Colitis

Study Overview
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Brief Summary
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To compare the safety and efficacy of concomitant LFMT versus placebo in UC patients who are starting vedolizumab or ustekinumab.

Detailed Description
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This is dual-center, randomized, double-blind, placebo-controlled pilot trial for UC patients with active disease who are being initiated on treatment with vedolizumab or ustekinumab. The study will recruit 40 outpatients at 2 Canadian healthcare centres at the University of Alberta Hospital (University of Alberta), and the Hamilton Health Sciences (McMaster University).

Official Title
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A Dual-center, Double Blind, Randomized Placebo-controlled Pilot Trial of Concomitant Lyophilized Fecal Microbiota Transplantation (LFMT) and Biologic Therapy (Vedolizumab or Ustekinumab) for the Induction of Remission in Ulcerative Colitis (UC)

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Lyophilized fecal microbiota (LFMT)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older but less than 75 years of age Able to provide informed consent Established ulcerative colitis diagnosis determined by a physician through standard endoscopic and histologic criteria Active UC defined as total Mayo score between 6-12 AND Mayo endoscopic sub-score >1 with disease that extends 15 cm or more from the anal verge Selected by treating physician for initiation of biologic treatment with either vedolizumab or ustekinumab. Patients must be: Biologic naive; OR Have failed anti-TNF, anti-integrin, anti IL12/23 or oral small molecules Use of effective contraception method for women of childbearing potential for at least 4 weeks prior to receiving study treatment and for the duration of the trial Willing and able to comply with all required study procedures Exclusion Criteria: Severe UC requiring hospitalization Indeterminate colitis Evidence of or treatment for C difficile infection or other intestinal pathogen, including CMV, within 4 weeks prior to enrollment Evidence of toxic megacolon or gastrointestinal perforation on imaging Abdominal surgery within the past 60 days Neutropenia with absolute neutrophil count <0.5 x 109/L Peripheral white blood cell count > 35.0 x 109/L and fever (>38 degrees Celsius) Planned or actively taking another investigational product Uncontrolled medical conditions such as psychiatric disorders or substance abuse Severe underlying disease such that the patient is not expected to survive for at least 30 days Pregnant or lactating Unwilling to discontinue non-dietary probiotic Antibiotic use in the past 30 days or anticipated need for systemic antibiotic use during study FMT within 3 months prior to enrollment Use of the following medications: rectal/topical therapy within 2 weeks of screening cyclosporine, tacrolimus or thalidomide within 4 weeks of screening tofacitinib within 4 weeks of screening adalimumab or infliximab within 8 weeks of screening vedolizumab within 8 weeks of screening ustekinumab within 12 weeks of screening prednisone > 30 mg/d Investigator deems enrolment in the study is not in the best interest of the patient

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LFMT capsules + vedolizumab<br>The initial loading dose is 15 capsules, administered on day 0, in the clinic under direct observation, followed by 5 capsules daily starting on day 1 for 8 weeks at home. All subsequent doses will be dispensed to participants. | Drug: Lyophilized fecal microbiota (LFMT)<br>* vedolizumab or ustekinumab + FMT vs placebo<br>|
| Placebo Comparator: Placebo capsules + vedolizumab<br>The placebo capsules will appear identical to the LFMT capsules; however, the capsules will contain 2 ingredients: trehalose and neusilin, which are components in LFMT capsules. | Other: Placebo<br>* Placebo<br>|
| Experimental: LFMT capsules + ustekinumab<br>The initial loading dose is 15 capsules, administered on day 0, in the clinic under direct observation, followed by 5 capsules daily starting on day 1 for 8 weeks at home. All subsequent doses will be dispensed to participants. | Drug: Lyophilized fecal microbiota (LFMT)<br>* vedolizumab or ustekinumab + FMT vs placebo<br>|
| Placebo Comparator: Placebo capsules + ustekinumab<br>The placebo capsules will appear identical to the LFMT capsules; however, the capsules will contain 2 ingredients: trehalose and neusilin, which are components in LFMT capsules. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with serious adverse events (SAEs) of interest up to week 8 in each group (ie vedolizumab with or without LFMT, ustekinumab with or without LFMT). | SAE of interest is defined as one of the following: An infection attributable to FMT Worsening UC, defined as requiring rescue therapy such as increase in steroid dose or change in biologic or colectomy Hospitalization due to UC or an infection attributable to FMT Mortality due to UC or an infection attributable to FMT SAE of interest is defined as one of the following: An infection attributable to FMT Worsening UC, defined as requiring rescue therapy such as increase in steroid dose or change in biologic or colectomy Hospitalization due to UC or an infection attributable to FMT Mortality due to UC or an infection attributable to FMT | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants in each group with adverse events during the study up to week 24, including nausea, vomiting, abdominal pain, worsening diarrhea, constipation or fevers |  | 24 weeks | 
| Proportion of participants who achieve clinical remission, defined as total Mayo score ≤ 2 with no individual subscore > 1, at week 8 and 24 in each group. |  | 24 weeks | 
| Proportion of participants who achieve clinical response | Defined as a reduction in the Mayo clinic score of ≥ 3 points and/ or ≥ 30% from baseline, with a decrease in the rectal bleeding subscore of ≥ 1 point or a subscore ≤ 1 at week 8 and 24 in each group | 24 weeks | 
| Proportion of participants who achieve symptom remission, defined as partial Mayo score < 2 with no individual subscore > 1, at week 8 and 24 in each group |  | 24 weeks | 
| Proportion of participants who achieve symptom response, defined as reduction in partial Mayo score ≥ 2 points from baseline and ≥ 30% from baseline and decrease in rectal bleeding score of ≥ 1point from baseline, at week 8 and 24 in each group |  | 24 weeks | 
| Proportion of participants who achieve endoscopic improvement, defined as Mayo endoscopic subscore ≤1, at week 8 and 24 in each group |  | 24 weeks | 
| Changes in partial Mayo score over time up to week 24 relative to baseline in each group |  | 24 weeks | 
| Changes in quality of life, assessed by short IBD Questionnaire (sIBDQ), and work productivity, assessed by Work Productivity and Activity Impairment Questionnaire (WPAIQ), at week 8 and 24 relative to baseline in each group |  | 24 weeks | 
| Changes in inflammatory markers (serum c-reactive protein (CRP) and fecal calprotectin) over time up to week 24 in each group |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FMT, Microbiome