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Fecal Microbiota Transplant (FMT) in Pediatric Active Ulcerative Colitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Boston Children’s Hospital
Sponsor:
Information provided by (Responsible Party):
Stacy A. Kahn, Boston Children's Hospital
ClinicalTrials.gov Identifier:
NCT02330653
First received: December 29, 2014
Last updated: March 16, 2017
Last verified: March 2017
  Purpose
The primary aim of this phase I/II, randomized, placebo controlled study is 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) who have previously failed traditional, first-line maintenance therapy (aminosalicylates) or are intolerant to 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.

Condition Intervention Phase
Inflammatory Bowel Diseases
Ulcerative Colitis
Biological: Fecal Microbiota Transplant
Biological: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Phase I/II, Double Blinded, Placebo Controlled, Single-center Study of Fecal Microbiota Transplant (FMT) for the Treatment of Active Pediatric Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by Boston Children’s Hospital:

Primary Outcome Measures:
  • Safety and tolerability of universal donor FMT compared to placebo: FMT-related adverse events grade 2 or above [ Time Frame: At 8 weeks after start of FMT ]
    Proportion of FMT-related adverse events grade 2 or above experienced in each arm.

  • Improvement in the Pediatric Ulcerative Colitis Activity Index (PUCAI) by 20 points or more. [ Time Frame: At 8 weeks after start of FMT ]
    Improvement in disease status as measured by improvement in PUCAI score by 20 points or more.


Secondary Outcome Measures:
  • Remission of disease [ Time Frame: At 8 weeks and 1 year after start of FMT ]
    Remission as defined by a PUCAI score of less than 9

  • Improvement in inflammatory biomarkers [ Time Frame: At 8 weeks and 1 year after start of FMT ]
    Improvement in inflammatory biomarkers (stool calprotectin, stool lactoferrin, serum ESR/CRP, albumin, Hematocrit) compared to baseline.

  • Safety and tolerability of universal donor FMT compared to placebo: FMT-related adverse events grade 2 or above [ Time Frame: At 1 year after start of FMT ]
    Proportion of FMT-related adverse events grade 2 or above experienced in each arm.

  • Improvement in the Pediatric Ulcerative Colitis Activity Index (PUCAI) by 20 points or more. [ Time Frame: at 1 year after start of FMT ]
    Improvement in disease status as measured by improvement in PUCAI score by 20 points or more.


Estimated Enrollment: 60
Study Start Date: March 2016
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fecal Microbiota Transplant
Induction retention enema for the first week of treatment followed by 10 capsules of study treatment (the equivalent of 30 grams of human stool) will be (administered within 60 minutes of thawing once weekly for a total of 7 weeks) for a total of 8 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 the remainder of the 6 month duration of the study (16 week).
Biological: Fecal Microbiota Transplant
The study intervention consists of frozen, bottled or encapsulated fecal microbiota preparations that have been screened and prepared to a uniform and rigorous standards by the Microbiome Health Research Institute Inc. FMT is performed by patients receiving a retention enema and swallowing capsules, introducing stool from a healthy donor into their intestinal tract.
Other Name: Screened, healthy human donor stool
Placebo Comparator: Placebo
Induction placebo enema for the first week of treatment followed by 10 capsules of study placebo (administered within 60 minutes of thawing once weekly for a total of 7 weeks) for a total of 8 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 the remainder of the 6 month duration of the study (16 week).
Biological: Placebo
Placebo administration will consist of both a placebo retention enema and placebo capsules.

Detailed Description:

This is a single-center, phase I/II, randomized, prospective, double-blinded, placebo-controlled study of FMT in the treatment of active pediatric UC. The primary aim is to assess safety and feasibility of a weekly FMT maintenance therapy. A total of 60 patients with active UC (as defined by PUCAI score of >9) 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 6 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 10 subjects will be enrolled and randomized to receive FMT or placebo. We'd expect short term adverse events to occur within 7 days of FMT administration. Subject safety data will be reviewed completely 7 days after all subjects have received at least 2 doses of study drug prior to continuing enrollment or 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.

  Eligibility

Ages Eligible for Study:   5 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 1. Have UC (PUCAI >9) and have failed traditional first-line maintenance therapy (aminosalicylates) or are intolerant to therapy.
  2. Have had visual or histologic evidence of inflammation confirmed through colonoscopy no more than 90 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.
  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. Patients with a history of CDI or have CDI at the time of enrollment will be included

Exclusion Criteria:

  1. Patients in a clinical remission (PUCAI < 9).
  2. Patients considered to have toxic megacolon.
  3. Treatment naïve patients, i.e., patients must be intolerant to or not have responded to aminosalicylates.
  4. Patients with a known drug allergy to vancomycin, metronidazole or polymyxin.
  5. Patients with a history of aspiration, gastroparesis, surgery involving the upper gastrointestinal tract (that might affect upper gastrointestinal motility) or unable to swallow pills.
  6. Patients with esophageal dysmotility or swallowing dysfunction.
  7. Patients with known food allergies.
  8. Patients with positive test results for HBV, HCV, or HIV.
  9. Female patients with a positive test result on a urine hCG test.
  10. Patients unwilling or unable to give consent or participate in all study requirements.
  11. Patients unable or unwilling to receive a retention enema for purposes of induction therapy
  12. Children with recent (within 4 weeks) dose change of biologics, 5-ASA, steroids or immunomodulators
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02330653

Contacts
Contact: Sean T Murphy 617-919-4609 fmt@childrens.harvard.edu

Locations
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Sean T Murphy       fmt@childrens.harvard.edu   
Sponsors and Collaborators
Stacy A. Kahn
Investigators
Principal Investigator: Stacy A Kahn, MD Boston Childrens Hospital - GI & Nutrition
  More Information

Responsible Party: Stacy A. Kahn, Associate Director of the Inflammatory Bowel Disease Center, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT02330653     History of Changes
Other Study ID Numbers: P00014876
Study First Received: December 29, 2014
Last Updated: March 16, 2017

Keywords provided by Boston Children’s Hospital:
Colitis
Fecal Microbiota Transplant
Ulcerative colitis
inflammatory bowel disease

Additional relevant MeSH terms:
Colitis
Ulcer
Colitis, Ulcerative
Intestinal Diseases
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on March 28, 2017