Fecal Microbiota Transplant for Autobrewery Syndrome

The goal of this clinical trial is to study fecal microbiota transplantation(FMT) by oral capsule in people already diagnosed with auto-brewery syndrome (ABS, also known as gut fermentation syndrome). The main question it aims to answer: Is FMT safe and feasible in this syndrome?

Participants will

1. have a "gut cleanout" with oral antibiotics and a colon cleanse, similar to that administered before colonoscopy
2. receive five oral doses of fecal transplant capsules over a week
3. be followed for six months for safety and research samples

Study Overview

• Status: Not yet recruiting
• Conditions: Auto-Brewery Syndrome; Gut Fermentation Syndrome
• Intervention / Treatment: Biological: Fecal microbiota transplantation capsules

Detailed Description

The study is a single arm, open label pilot safety and feasibility study. Subjects will provide medical information related to their diagnosis of ABS. All subjects will have a baseline assessment (medical history, exam, blood and stool samples ) at Massachusetts General Hospital in Boston. Those enrolled will receive a gut clean out procedure and 5 doses of FMT capsules in the 7 days after the clean out. Each individual ABS patient will receive capsules generated from a single donor, to minimize the risk of transmission of infectious agents. All subjects receive active treatment; there is no placebo.

The primary objective of this study is to evaluate the safety and feasibility of the proposed procedures (antibiotic pretreatment, "clean out" and microbial restoration via capsule FMT), thus the primary endpoints will be collection of data regarding any FMT-related adverse events. Feasibility will be defined as taking 3 doses of FMT capsules which we believe can fully reconstitute a healthy microbiome based upon our and others work.

Safety will be assessed daily for 7 days after FMT, and the intermitently over the 6 months after FMT, using standardized patient report scales and interviews as well as by clinical laboratories (at baseline and 2 weeks 2 months, and 6 months). Feasibility is defined as all subjects completing at least 3/5 planned doses of FMT capsules.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Elizabeth Hohmann, MD; Phone Number: 617-724-7532; Email: ehohmann@partners.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-70 with documented ABS symptoms for at least one year, including supervised ethanol testing or a positive glucose challenge test in a supervised setting.
• Active ABS including at least 3 flares by either serum or breath alcohol levels in the past year (blood or breath samples)
• Subject's microbiome produces alcohol ex vivo in bioreactor (Schnabl laboratory)
• Willing and able to travel to Boston for in person assessment (modest reimbursement available)
• Willing to stop antifungals, and any other complimentary therapies for ABS, if taking
• Medically able to withstand clean out. If participants are over 60, the subject must have previously tolerated a prior colonoscopic "prep" as part of prior routine care.
• Local physician contact available

Exclusion Criteria:

• Unwilling/unable to swallow large capsules (e.g.esophageal stricture or hiatal hernia)
• Delayed gastric emptying syndrome
• Known chronic aspiration, or chronic nausea/vomiting
• Pregnant (pregnancy testing will be performed in women of childbearing potential; women over 52 with no menses for 12 months will not require testing)
• Patients with an acute active illness or acute exacerbation of underlying comorbid condition.
• Patients on unstable, or increasing immunosuppressive agents including high dose corticosteroids(40 mg prednisone daily or more), calcineurin inhibitors, escalating immunosuppression for organ rejection, active chemotherapy with expected neutropenia, current or neutropenia (ANC <1000) within the last year.
• Patients with decompensated cirrhosis, advanced HIV/AIDS, recent bone marrow transplant, or other severe immunodeficiency.
• Severe food allergy or intolerance (donors are omnivores and do not maintain dietary restrictions)
• Cannot document at least 2 COVID vaccinations. Those refusing all COVID vaccination are not eligible for FMT.
• Ulcerative colitis or Crohn's disease (microbiome manipulation may precipitate a flare of these illnesses).
• Active HIV, hepatitis B or C infection (subjects with prior treated hepatitis C must have undetectable viral load; HIV positive subjects must be receiving anti-retroviral therapy with undetectable viral loads x 1 year minimum, Hepatitis B core antibody positive subjects are allowed if negative HepB surface antigen and antibody)
• Taking warfarin (known to be affected by dietary and microbiome changes). NOACs do not exclude.
• On suppressive antibacterial agents, or expected to receive prophylactic antibacterials within the year, for example a patient with a prosthetic heart valve who routinely receives dental prophylaxis, or patient with chronic UTIs anticipated to need treatment frequently
• Known biliary structural abnormalities.
• Allergy to erythromycin, neomycin, or rifaximin.
• Type I diabetes mellitus
• History of pancreatitis or biliary sepsis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active FMT; Active FMT (5 doses) over 7 days. Each dose contains 15 capsules.	Biological: Fecal microbiota transplantation capsules; Fecal microbiota transplantation capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	Safety outcomes of special interest include: Fever, diarrhea, nausea, vomiting, pain/bloating, bacteremia or transmission of GI infection	Over 6 months.
Adequate dosing of FMT	Adequate dosing is defined as subjects completed the gut cleanse and ingesting at least 3/5 planned doses of FMT capsules	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Alcohol Level	Plasma blood alcohol level	Over 6 months
Stool bioreactor ethanol production	Presence or absence of elevated alcohol level when stool is cultured in a bioreactor	Over 6 monthis
weight	Subject weight in kg	over 6 months
Microbiome analysis of stool samples	Comparison of stool microbiome to subject's baseline and donor	over 6 months.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: University of California, San Diego
• Investigators: Principal Investigator: Elizabeth Hohmann, MD, MGH

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2030

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: October 12, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: fecal microbiota transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome
• Other Study ID Numbers: 2023p000579

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: conded data will be shared upon request
• IPD Sharing Time Frame: At completion of study
• IPD Sharing Access Criteria: upon request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No