Clinical trial NCT05327790: LFMT vs Placebo in New Biologic Start for Ulcerative Colitis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: FMT
Microbiome
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2022-04-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. 18 years of age or older but less than 75 years of age
2. Able to provide informed consent
3. Established ulcerative colitis diagnosis determined by a physician through standard endoscopic and histologic criteria
4. 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
5. 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
6. 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
7. Willing and able to comply with all required study procedures

Exclusion Criteria:

1. Severe UC requiring hospitalization
2. Indeterminate colitis
3. Evidence of or treatment for C difficile infection or other intestinal pathogen, including CMV, within 4 weeks prior to enrollment
4. Evidence of toxic megacolon or gastrointestinal perforation on imaging
5. 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
6. Pregnant or lactating
7. Unwilling to discontinue non-dietary probiotic
8. Antibiotic use in the past 30 days or anticipated need for systemic antibiotic use during study
9. FMT within 3 months prior to enrollment
10. Use of the following medications:

    1. rectal/topical therapy within 2 weeks of screening
    2. cyclosporine, tacrolimus or thalidomide within 4 weeks of screening
    3. tofacitinib within 4 weeks of screening
    4. adalimumab or infliximab within 8 weeks of screening
    5. vedolizumab within 8 weeks of screening
    6. ustekinumab within 12 weeks of screening
    7. prednisone \> 30 mg/d
11. Investigator deems enrolment in the study is not in the best interest of the patient

Primary outcomes:
measure: 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).
timeFrame: 24 weeks
Secondary outcomes:
measure: 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
timeFrame: 24 weeks
measure: 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.
timeFrame: 24 weeks
measure: Proportion of participants who achieve clinical response
timeFrame: 24 weeks
measure: 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
timeFrame: 24 weeks
measure: 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
timeFrame: 24 weeks
measure: Proportion of participants who achieve endoscopic improvement, defined as Mayo endoscopic subscore ≤1, at week 8 and 24 in each group
timeFrame: 24 weeks
measure: Changes in partial Mayo score over time up to week 24 relative to baseline in each group
timeFrame: 24 weeks
measure: 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
timeFrame: 24 weeks
measure: Changes in inflammatory markers (serum c-reactive protein (CRP) and fecal calprotectin) over time up to week 24 in each group
timeFrame: 24 weeks
Other outcomes:
measure: Proportion of participants with Corticosteroid-free remission at week 8 and 24
timeFrame: 24 weeks
measure: Time to clinical remission, clinical response, symptom remission and symptom response in each group
timeFrame: 24 weeks
measure: Changes in stool microbiome at week 8 and 24 relative to baseline in each group
timeFrame: 24 weeks
measure: Changes in stool microbiome at time of remission relative to baseline in each group
timeFrame: 24 weeks
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
Study officials:
References: