Back to results

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

Primary Purpose

Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Fecal Microbiota Transplant (FMT)

Placebo

About this trial

This is an interventional treatment trial for Inflammatory Bowel Diseases focused on measuring Colitis, Fecal Microbiota Transplant, Ulcerative colitis, inflammatory bowel disease, Crohn's Disease

Eligibility Criteria

5 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

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:

Have UC (PUCAI >9) or CD (PDCAI >10) and have failed, are intolerant to, or have refused first-line maintenance therapy.
Have had visual or histologic evidence of inflammation confirmed through colonoscopy no more than 105 days prior to randomization.
Have negative test results for Hepatitis B (HBV), Hepatitis C (HCV), and Human Immunodeficiency Virus (HIV).
Have a negative urine hCG test if female of childbearing potential.
Able to swallow antibiotic, FMT or placebo capsules.
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)
Willing and able to participate in the study requirements, including serial stool collection, survey completion and clinic visits.
Willing to undergo telephone follow-up to assess for safety and adverse events.
Must be free of any known food allergy.
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.

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.

Sites / Locations

Boston Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Fecal Microbiota Transplant (FMT)

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

1. Safety and Tolerability of Universal Donor FMT Compared to Placebo: FMT-related Adverse Events Grade 2 or Above

Number of participants with FMT-related adverse events grade 2 or above experienced in each arm.

Secondary Outcome Measures

Remission of Disease

Remission as defined by a PUCAI score of less than 9 (for UC) or by a PCDAI score of less than 10 (for CD)

Improvement in Inflammatory Biomarkers

Improvement in inflammatory biomarkers (stool calprotectin, serum ESR, CRP, albumin, hematocrit) compared to baseline.

Percentage of Donor Microbiome Present in Transplant Recipient

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.

Number of Participants With Improvement in Disease Activity

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.

Full Information

NCT ID

NCT02330653

First Posted

December 29, 2014

Last Updated

October 12, 2023

Sponsor

Stacy A. Kahn

1. Study Identification

Unique Protocol Identification Number

NCT02330653

Brief Title

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

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 and Pediatric Active Crohn's Colitis

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Completed

Study Start Date

November 2015 (Actual)

Primary Completion Date

April 8, 2019 (Actual)

Study Completion Date

April 8, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Stacy A. Kahn

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn Disease

Keywords

Colitis, Fecal Microbiota Transplant, Ulcerative colitis, inflammatory bowel disease, Crohn's Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fecal Microbiota Transplant (FMT)

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Fecal Microbiota Transplant (FMT)

Other Intervention Name(s)

Screened, healthy human donor stool

Intervention Description

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

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

1. Safety and Tolerability of Universal Donor FMT Compared to Placebo: FMT-related Adverse Events Grade 2 or Above

Description

Number of participants with FMT-related adverse events grade 2 or above experienced in each arm.

Time Frame

At 8 weeks after start of FMT up to 6 months post treatment, an average of 10 months

Secondary Outcome Measure Information:

Title

Remission of Disease

Description

Remission as defined by a PUCAI score of less than 9 (for UC) or by a PCDAI score of less than 10 (for CD)

Time Frame

At all intermediate timepoints until 6 month follow up post intervention, an average of 10 months

Title

Improvement in Inflammatory Biomarkers

Description

Improvement in inflammatory biomarkers (stool calprotectin, serum ESR, CRP, albumin, hematocrit) compared to baseline.

Time Frame

At End of Treatment (8 weeks) and at 6 month post treatment

Title

Percentage of Donor Microbiome Present in Transplant Recipient

Description

Time Frame

At two weeks and seven weeks post induction enema

Title

Number of Participants With Improvement in Disease Activity

Description

Time Frame

At 8 weeks after start of FMT

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility 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. 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: Have UC (PUCAI >9) or CD (PDCAI >10) and have failed, are intolerant to, or have refused first-line maintenance therapy. Have had visual or histologic evidence of inflammation confirmed through colonoscopy no more than 105 days prior to randomization. Have negative test results for Hepatitis B (HBV), Hepatitis C (HCV), and Human Immunodeficiency Virus (HIV). Have a negative urine hCG test if female of childbearing potential. Able to swallow antibiotic, FMT or placebo capsules. 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) Willing and able to participate in the study requirements, including serial stool collection, survey completion and clinic visits. Willing to undergo telephone follow-up to assess for safety and adverse events. Must be free of any known food allergy. 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stacy A Kahn, MD

Organizational Affiliation

Boston Childrens Hospital - GI & Nutrition

Official's Role

Principal Investigator

Facility Information:

Facility Name

Boston Children's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs