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

Crohn Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02330211
• Other study ID #: P00014880
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 17, 2017
• Est. completion date: August 30, 2018

Study information

• Verified date: January 2019
• Source: Boston Children’s Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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 information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: August 30, 2018
• Est. primary completion date: August 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 30 Years

Eligibility

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 less than or equal to 30) and to individuals greater than or equal to 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 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:

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.

Related Conditions & MeSH terms

• Colitis
• Crohn Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

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 OpenBiome. FMT is performed by patients receiving a retention enema and swallowing capsules, introducing stool from a healthy donor into their intestinal tract.
• Placebo
Placebo administration will consist of both a placebo retention enema and placebo capsules.

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Stacy A. Kahn

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of universal donor FMT compared to placebo: FMT-related adverse events of grade 2 or above	Proportion of subjects with any FMT-related adverse events of grade 2 or above.	At 8 weeks after start of FMT
Primary	Improvement Pediatric Crohn's Disease Activity Index (PCDAI) by 12.5 points or more	Improvement of disease status as measured by improvement of PCDAI score of 12.5 points or more.	At 8 weeks after start of FMT
Secondary	Remission of disease	Remission of disease as defined by PCDAI score of 10 or less	At 8 weeks and 1 year after start of FMT
Secondary	Identify biomarkers that may confer a clinical response	Improvement in inflammatory biomarkers (stool calprotectin, stool lactoferrin, serum ESR/CRP, albumin, Hematocrit) compared to baseline.	At 8 weeks and 1 year after start of FMT
Secondary	Safety and tolerability of universal donor FMT compared to placebo: FMT-related adverse events of grade 2 or above	Proportion of subjects with any FMT-related adverse events of grade 2 or above.	At 1 year after start of FMT
Secondary	Improvement Pediatric Crohn's Disease Activity Index (PCDAI) by 12.5 points or more	Improvement of disease status as measured by improvement of PCDAI score of 12.5 points or more.	At 1 year after start of FMT