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

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ClinicalTrials.gov Identifier: NCT02330211
Recruitment Status : Recruiting
First Posted : January 1, 2015
Last Update Posted : November 14, 2017
Sponsor:
Information provided by (Responsible Party):
Stacy A. Kahn, Boston Children’s Hospital

Brief Summary:
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 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 CD.

Condition or disease Intervention/treatment Phase
Inflammatory Bowel Diseases Crohn Disease Biological: Fecal Microbiota Transplant Biological: Placebo Phase 1 Phase 2

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 CD. The primary aim is to assess safety and feasibility of a weekly FMT maintenance therapy. A total of 60 patients with active CD (as defined by PCDAI 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 10 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 Crohn's 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 PIto 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (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 Crohn's Colitis
Actual Study Start Date : July 17, 2017
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Fecal Microbiota Transplant
Induction retention enema for the first week of treatment followed by 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 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 an additional 8 weeks.
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 15 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 an additional 8 weeks.
Biological: Placebo
Placebo administration will consist of both a placebo retention enema and placebo capsules.




Primary Outcome Measures :
  1. Safety and tolerability of universal donor FMT compared to placebo: FMT-related adverse events of grade 2 or above [ Time Frame: At 8 weeks after start of FMT ]
    Proportion of subjects with any FMT-related adverse events of grade 2 or above.

  2. Improvement Pediatric Crohn's Disease Activity Index (PCDAI) by 12.5 points or more [ Time Frame: At 8 weeks after start of FMT ]
    Improvement of disease status as measured by improvement of PCDAI score of 12.5 points or more.


Secondary Outcome Measures :
  1. Remission of disease [ Time Frame: At 8 weeks and 1 year after start of FMT ]
    Remission of disease as defined by PCDAI score of 10 or less

  2. Identify biomarkers that may confer a clinical response [ 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.

  3. Safety and tolerability of universal donor FMT compared to placebo: FMT-related adverse events of grade 2 or above [ Time Frame: At 1 year after start of FMT ]
    Proportion of subjects with any FMT-related adverse events of grade 2 or above.

  4. Improvement Pediatric Crohn's Disease Activity Index (PCDAI) by 12.5 points or more [ Time Frame: At 1 year after start of FMT ]
    Improvement of disease status as measured by improvement of PCDAI score of 12.5 points or more.



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

Inclusion Criteria:

Male and female children and young adults, aged 5 years to 30 years, who meet the following inclusion criteria, will be enrolled in the study.

An initial subset of 10 subjects will be limited to patients with mild to moderate Crohn's disease (i.e., PCDAI < 30) and to individuals > 12 years of age. If FMT appears to be safe in this subset of patients after 8 weeks in the study (to be assessed by a Data Safety Monitoring Board), expanded enrollment as is described above will occur.

All patients must satisfy below criteria:

  1. Have Crohn's colitis (PCDAI >10) and have failed, are intolerant to, or have refused traditional first-line maintenance 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 (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:

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

  1. Patients with extensive and/or severe CD (i.e. fistulizing disease, abscess, small bowel obstruction, fevers).
  2. Patients in a clinical remission (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 polymixin.
  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

Research personnel and care providers will be educated about inclusion/exclusion criteria so that only appropriate patients are approached for informed consent. This will reduce the burden of worry for families and patients as to whether they are suitable candidates for the study. Subjects who are found to have no evidence of active disease by colonoscopy will be excluded from the study.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02330211


Contacts
Contact: McKenzie M Leier 617-919-4609 fmt@childrens.harvard.edu

Locations
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: McKenzie M Leier    617-919-4609    fmt@childrens.harvard.edu   
Sponsors and Collaborators
Stacy A. Kahn
Investigators
Principal Investigator: Stacy A Kahn, MD Boston Childrens Hospital - GI & Nutrition

Responsible Party: Stacy A. Kahn, Associate Chief of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT02330211     History of Changes
Other Study ID Numbers: P00014880
First Posted: January 1, 2015    Key Record Dates
Last Update Posted: November 14, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Stacy A. Kahn, Boston Children’s Hospital:
Colitis
Fecal Microbiota Transplant
Crohn's Disease
inflammatory bowel disease

Additional relevant MeSH terms:
Crohn Disease
Colitis
Intestinal Diseases
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases