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

NCT ID: NCT02330653

Last Updated: 2023-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2019-04-08

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.

Conditions

Inflammatory Bowel Diseases; Ulcerative Colitis; Crohn Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Fecal Microbiota Transplant (FMT)

Intervention Type: BIOLOGICAL

The study intervention consists of frozen, bottled or encapsulated fecal microbiota preparations that have been screened and prepared to a uniform and rigorous standard by OpenBiome. FMT is performed by patients receiving a retention enema and swallowing capsules, introducing stool from a healthy donor into their intestinal tract.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo administration will consist of both a placebo retention enema and placebo capsules.

Interventions

Fecal Microbiota Transplant (FMT)

The study intervention consists of frozen, bottled or encapsulated fecal microbiota preparations that have been screened and prepared to a uniform and rigorous standard by OpenBiome. FMT is performed by patients receiving a retention enema and swallowing capsules, introducing stool from a healthy donor into their intestinal tract.

Intervention Type: BIOLOGICAL

Placebo

Placebo administration will consist of both a placebo retention enema and placebo capsules.

Intervention Type: BIOLOGICAL

Other Intervention Names

Screened, healthy human donor stool

Eligibility Criteria

Inclusion Criteria

Two initial subsets will be created: an initial subset of 20 subjects limited to patients greater than or equal to 12 years of age with mild to moderate ulcerative colitis (i.e., PUCAI < 65) patients with mild to moderate Crohn's disease (i.e., PDCAI less than or equal to 30).

All patients must satisfy below criteria:

1. Have UC (PUCAI >9) or CD (PDCAI >10) and have failed, are intolerant to, or have refused first-line maintenance therapy.

2. Have had visual or histologic evidence of inflammation confirmed through colonoscopy no more than 105 days prior to randomization.

3. Have negative test results for Hepatitis B (HBV), Hepatitis C (HCV), and Human Immunodeficiency Virus (HIV).

4. Have a negative urine hCG test if female of childbearing potential.

5. Able to swallow antibiotic, FMT or placebo capsules.

6. Able to give informed consent and/or assent as appropriate (patients 12-17 will be asked to provide written assent, patients 5-11 will be observed for assent or dissent behaviorally, or with verbal/written communication)

7. Willing and able to participate in the study requirements, including serial stool collection, survey completion and clinic visits.

8. Willing to undergo telephone follow-up to assess for safety and adverse events.

9. Must be free of any known food allergy.

10. Agrees and willing to have an enema for purposes of induction therapy.

Patients who have disease that has required other medications (including steroids, immunosuppressives, and biologics) will be included.

Exclusion Criteria

1. Patients with extensive and/or severe CD (i.e. fistulizing disease, abscess, small bowel obstruction, fevers).

2. Patients in a clinical remission (PUCAI < 9) or (PCDAI <10).

3. Patients with recent (within 4 weeks) dose change of biologics, 5-ASA, steroids or immunomodulators

4. Patients considered to have toxic megacolon.

5. Patients with a known drug allergy to vancomycin, metronidazole or polymyxin.

6. Patients with a history of aspiration, gastroparesis, surgery involving the upper gastrointestinal tract (that might affect upper gastrointestinal motility) or unable to swallow pills.

7. Patients with esophageal dysmotility or swallowing dysfunction.

8. Patients with known food allergies.

9. Patients with positive test results for HBV, HCV, or HIV.

10. Female patients with a positive test result on a urine hCG test.

11. Patients unwilling or unable to give consent or participate in all study requirements.

12. Patients unable or unwilling to receive a retention enema for purposes of induction therapy.

13. Patients with recent (within 6 weeks) systemic antibiotic use.

14. Patients who have testing consistent with active clostridium difficile.

15. Patients with known prior experience with donor FMT.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stacy A. Kahn

OTHER

Sponsor Role: lead

Responsible Party

Stacy A. Kahn

Associate Director of the Inflammatory Bowel Disease Center

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Stacy A Kahn, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Childrens Hospital - GI & Nutrition

Locations

Boston Children's Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P00014876

Identifier Type: -

Identifier Source: org_study_id

NCT02330211

Identifier Type: -

Identifier Source: nct_alias