Fecal Microbiota Transplant (FMT) in Pediatric Active Ulcerative Colitis and Pediatric Active Crohn's Colitis

Phase 1

Completed

Conditions: Inflammatory Bowel Diseases
Crohn Disease
Ulcerative Colitis

Interventions: Biological: Fecal Microbiota Transplant (FMT)
Biological: Placebo

Registration Number: NCT02330653

Lead Sponsor: Stacy A. Kahn

Brief Summary: The primary aims of this phase I/II, randomized, placebo controlled study are the assessment of safety and tolerability of universal donor FMT compared to placebo in pediatric and young adult subjects (ages 5 years through 30 years) with active ulcerative colitis (UC) or active Crohn's colitis (CD) who have failed, are intolerant to, or have refused traditional first-line maintenance therapy. Secondary objectives include the identification biomarkers in both donor and recipient that may confer a clinical response and to establish whether or not ongoing FMT maintenance therapy is required for maintenance of clinical benefit in pediatric UC or pediatric CD.

Detailed Description: This is a single-center pilot, phase I/II, randomized, prospective, double-blinded, placebo-controlled study of FMT in the treatment of active pediatric UC and active pediatric CD. The primary aim is to assess safety and feasibility of a weekly FMT maintenance therapy. A total of 10 patients with active UC (as defined by PUCAI score of \>9) and 10 patients with active CD (as defined by PDCAI score of \>10) will be enrolled and randomized to receive FMT or placebo-FMT (study treatment) by retention enema for 1 week and oral, frozen encapsulated inocula/placebo for 7 weeks. After the first 8 weeks, subjects on FMT who improve or subjects on placebo-FMT who do not improve will have the option to continue on study treatment or switch to open-label FMT until the end of 4 months from study initiation. Subjects will be followed by telephone to assess adverse events for a total of 6 months after their last FMT dose.

An initial subset of no more than 20 subjects will be enrolled in the study (will be limited to only those patients 12 years of age or older and to those who have mild to moderate disease) and randomized to receive FMT or placebo. We'd expect short term adverse events to occur within 7 days of FMT administration. Individual subject safety data will be reviewed by the PI to assess whether FMT appears to be safe in the subject before continuing the subject towards open-label use of FMT.

Patient metadata and stool samples will be collected at key time points. The patient-reported metadata collection technique will allow for numerous clinical correlations to be parsed out using the random forest machine learning capabilities of synthetic learning in microbial ecology (SLiME) to identify taxonomic features associated with important clinical parameters.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

Inclusion Criteria

Not provided

Exclusion Criteria

Subjects who fall into any of the following exclusion criteria at the time of screening are not eligible for enrollment into the study.

Patients with extensive and/or severe CD (i.e. fistulizing disease, abscess, small bowel obstruction, fevers).
Patients in a clinical remission (PUCAI < 9) or (PCDAI <10).
Patients with recent (within 4 weeks) dose change of biologics, 5-ASA, steroids or immunomodulators
Patients considered to have toxic megacolon.
Patients with a known drug allergy to vancomycin, metronidazole or polymyxin.
Patients with a history of aspiration, gastroparesis, surgery involving the upper gastrointestinal tract (that might affect upper gastrointestinal motility) or unable to swallow pills.
Patients with esophageal dysmotility or swallowing dysfunction.
Patients with known food allergies.
Patients with positive test results for HBV, HCV, or HIV.
Female patients with a positive test result on a urine hCG test.
Patients unwilling or unable to give consent or participate in all study requirements.
Patients unable or unwilling to receive a retention enema for purposes of induction therapy.
Patients with recent (within 6 weeks) systemic antibiotic use.
Patients who have testing consistent with active clostridium difficile.
Patients with known prior experience with donor FMT.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fecal Microbiota Transplant (FMT)	Fecal Microbiota Transplant (FMT)	Induction retention enema for the first week of treatment followed by once weekly administration of 15 capsules of study treatment (the equivalent of 7.5 grams of human stool) will be (administered within 60 minutes of thawing once weekly) for 7 weeks. After completing 8 weeks of blinded study treatment, study subjects on FMT who have shown improvement will be given the option to receive open-label maintenance FMT weekly for an additional 8 weeks of once weekly FMT capsule administration.
Placebo	Placebo	Induction placebo enema for the first week of treatment followed by once weekly administration of 15 capsules of study placebo (administered within 60 minutes of thawing once weekly) for 7 weeks. After completing 8 weeks of blinded study placebo, study subjects on placebo who DO NOT demonstrate improvement will be given the option to receive open-label maintenance FMT weekly for an additional 8 weeks, beginning with a FMT induction enema followed by 7 weeks of weekly FMT capsule administration.

Primary Outcome Measures

Name	Time	Method
1. Safety and Tolerability of Universal Donor FMT Compared to Placebo: FMT-related Adverse Events Grade 2 or Above	At 8 weeks after start of FMT up to 6 months post treatment, an average of 10 months	Number of participants with FMT-related adverse events grade 2 or above experienced in each arm.

Secondary Outcome Measures

Name	Time	Method
Remission of Disease	At all intermediate timepoints until 6 month follow up post intervention, an average of 10 months	Remission as defined by a PUCAI score of less than 9 (for UC) or by a PCDAI score of less than 10 (for CD)
Percentage of Donor Microbiome Present in Transplant Recipient	At two weeks and seven weeks post induction enema	We will assess changes in microbial composition and the extent of microbial engraftment from the donor in the recipient by comparing the similarity of the microbiomes at two weeks at seven weeks after the induction enema.
Improvement in Inflammatory Biomarkers	At End of Treatment (8 weeks) and at 6 month post treatment	Improvement in inflammatory biomarkers (stool calprotectin, serum ESR, CRP, albumin, hematocrit) compared to baseline.
Number of Participants With Improvement in Disease Activity	At 8 weeks after start of FMT	5a. For UC - Improvement of Pediatric Ulcerative Colitis Activity Index (PUCAI) by 20 points or more. Improvement in disease status as measured by improvement of PUCAI score by 20 points or more. 5b. For CD - Improvement of Pediatric Crohn's Disease Activity Index (PCDAI) by 12.5 points or more. Improvement of disease status as measured by improvement of PCDAI score by 12.5 points or more.