Fecal Microbiota Transplantation for Chronic Granulomatous Disease-Associated Colitis

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT05333471

Collaborator

(none)

Enrollment

Location

Arm

30.8

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

Chronic granulomatous disease (CGD) weakens the body's defense against germs. CGD can also damage the colon. It can cause inflammation (colitis) that disrupts the good bacteria. Placing good bacteria from donor stool into the intestine of a person with CGD (called fecal microbiota transplantation, or FMT) may help.

Objective:

To see if FMT can reduce inflammation in the colon.

Eligibility:

People aged 10-60 who have CGD and colitis, and the treatments they have tried are not helping or have side effects.

Design:

Participants will have a telehealth screening visit. They will have a medical record review and medical history. They will collect stool samples at home and mail them to NIH.

Participants will stay at the NIH hospital for 3-5 days. Each day, they will have the following:

Physical exam

Medical history and medicine review

Surveys about CGD and how it affects their life

Blood, stool, and urine tests

Participants will have a colonoscopy. They will be sedated. A long, flexible tube will be inserted into their rectum. The tube will deliver the FMT material to their colon. Small samples of intestinal tissue will be collected.

Participants may have an optional MRI of the digestive tract.

Participants will have 9 follow-up telehealth visits over 6 months. They will be asked about their symptoms and side effects. They will fill out short surveys. They will collect stool and urine samples at home. Up to 2 visits can be done in person. At these visits, they may have the option to have an MRI and another colonoscopy to get more tissue samples.

Participation will last for 6-7 months.

Condition or Disease	Intervention/Treatment	Phase
Chronic Granulomatous Disease-associated Colitis	Drug: OpenBiome FMT product FMP250	Phase 1/Phase 2

Detailed Description

Study Description:

This is a prospective, single-site, single-arm, open-label pilot trial to evaluate the use of fecal microbiota transplantation (FMT) delivered by colonoscopy as a treatment for chronic granulomatous disease (CGD)-associated colitis (AC). Participants will be evaluated for changes in intestinal inflammation, the microbiome, and symptoms associated with CGD-AC. It is hypothesized that FMT will reduce intestinal inflammation as measured by fecal calprotectin within 1 month compared to baseline (pre-FMT); there will be associated changes in the underlying stool microbiome and improvement in clinical symptoms.

Primary Objective:

To evaluate the change in intestinal inflammation pre-FMT vs post-FMT.

Secondary Objectives:

To evaluate the change in the stool microbiome pre-FMT vs post-FMT.
To evaluate changes in clinical symptoms pre-FMT and post-FMT.
Preliminary evaluation of the safety of FMT in CGD-AC.

Tertiary/Exploratory Objectives:

To evaluate other markers of intestinal and systemic inflammation pre-FMT and post-FMT.
To evaluate a washout period for beneficial effects of FMT on fecal calprotectin and the microbiome.
To evaluate the effect of FMT on antibiotic resistance in CGD-AC.

Primary Endpoint:

Difference in fecal calprotectin pre-FMT within 1 month post-FMT.

Secondary Endpoints:

Differences in alpha diversity, beta diversity, and relative abundance of taxa pre-FMT and within 1 month post-FMT. Assessment of engraftment of donor microbiome.
Difference in Patient Reported Outcome-2 (PRO-2) pre-FMT and within 1 month post-FMT.
Treatment-emergent adverse events (TEAEs).

Tertiary/Exploratory Endpoints:

Changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) pre-FMT and post-FMT; changes in Simple Endoscopic Score for Crohn s Disease (SES-CD) pre-FMT and post-FMT in those who undergo a second colonoscopy; changes in magnetic resonance (MR) enterography findings in those who undergo a second MR enterography.
Changes in fecal calprotectin and microbiome indices over 6 months post-FMT.
Changes in antibiotic resistance genes in stool microbiome pre-FMT and post-FMT.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study of Fecal Microbiota Transplantation for Chronic Granulomatous Disease-Associated Colitis

Actual Study Start Date :

Aug 8, 2022

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Interventional As this is a single arm study, this arm includes all participants. Participants will receive fecal microbiota transplantation (FMT) delivered by colonoscopy as a treatment for chronic granulomatous disease (CGD)-associated colitis (AC).	Drug: OpenBiome FMT product FMP250 Participants who weigh equal 20 kg will be instilled with 230 mL of the OpenBiome lower GI FMT product via colonoscopy. Participants who weigh <20 kg will be instilled with 10 mL/kg. The product will be delivered in the cecum is possible. If a full colonoscopy is not possible, then the product may be delivered more distally in the colon.

Arm

Intervention/Treatment

Experimental: Interventional

As this is a single arm study, this arm includes all participants. Participants will receive fecal microbiota transplantation (FMT) delivered by colonoscopy as a treatment for chronic granulomatous disease (CGD)-associated colitis (AC).

Drug: OpenBiome FMT product FMP250

Participants who weigh equal 20 kg will be instilled with 230 mL of the OpenBiome lower GI FMT product via colonoscopy. Participants who weigh <20 kg will be instilled with 10 mL/kg. The product will be delivered in the cecum is possible. If a full colonoscopy is not possible, then the product may be delivered more distally in the colon.

Outcome Measures

Primary Outcome Measures

Difference in fecal calprotectin pre FMT and within 1 month post FMT. [Within 1 month]
To evaluate the change in intestinal inflammation pre-FMT vs post FMT

Secondary Outcome Measures

Difference in PRO-2 pre-FMT and within 1 month post-FMT. [Within 1 month]
To evaluate changes in clinical symptoms pre-FMT and post FMT.
Differences in alpha diversity, beta diversity, and relative abundance of taxa pre-FMT within 1 month post-FMT and assessment of engraftment of donor microbiome and Assessment of engraftment of donor microbiome. [Within 1 month]
To evaluate the change in the stool microbiome pre-FMT vs post-FMT.

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Aged >=10 to <=60 years.
Able to provide informed consent (for ages >=18 years) or has a parent or guardian who can provide informed consent on their behalf (for ages <18 years).
Have confirmed prior diagnoses of CGD and CGD-AC (or CGD-IBD with evidence of colitis on colonoscopy).
Fecal calprotectin level >=200 microgram/g.
No planned change in systemic antibiotic regimen for CGD for 1 month preceding FMT.
No planned escalation in CGD-IBD treatment for 1 month preceding FMT.
Participants who can become pregnant must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy, starting at screening until the end of study participation. Highly effective methods include a barrier (eg, condom, diaphragm, cervical cap), intrauterine device, or hormonal contraception.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

Evidence of acute GI infection, including active GI abscesses.
Presence of C difficile toxin gene in stool, as identified by PCR, in screening period.
History of intestinal obstruction.
History of fistulizing CGD-IBD or CGD-IBD intra-abdominal abscesses.
History of CGD-IBD related non-transversable intestinal strictures.
History of AEs attributable to previous FMT.
History of significant liver disease (eg, biopsy-proven nodular regenerative hyperplasia), including portal hypertension or cirrhosis.
Use of monoclonal antibodies within the last 3 months.
Pregnant or breastfeeding.
History of severe food allergy.
Any contraindication to having colonoscopy under anesthesia.
Any condition that, in the opinion of the investigator, contraindicates participation in this study.