Fecal Microbiota Transplant as Treatment of Hepatic Encephalopathy

NCT03420482 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 2017P002296
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A common complication of advanced liver disease is a condition called hepatic encephalopathy, which leads to confusion. The current treatment options cause side effects, are costly, and do not always work. An abnormal population of bacteria in the intestines may be causing this condition, and transplanting bacteria from the colon of a healthy person may treat it. In this research study, the investigators will first find two healthy stool donors whose stool donation improves the gut bacteria of patients with advanced liver disease and helps them think more clearly. Then, in a randomized controlled trial, the investigators will compare the ability of stool donation from these two best donors versus a placebo to improve the neurological function of patients with advanced liver disease. If the investigators find the expected results, there will be a new effective therapy for patients with advanced liver disease and the very troublesome complication of hepatic encephalopathy.

Conditions

Hepatic Encephalopathy

Keywords

Microbiome; Fecal Microbiota Transplant

Outcome Measures

Primary Outcomes (1)

• Psychometric Hepatic Encephalopathy Score (PHES)

  The PHES is a validated assessment tool specifically designed for HE trials to test cognitive and psychomotor processing speed and visuomotor coordination. The PHES is a battery of 5 pencil-paper tests, completed in 15-20 minutes. The primary outcome is the change in PHES score from immediately before FMT to 1 week after the last dose of FMT.

  Before the first administration of FMT (day 0) and one week after the last administration of FMT (day 28)

Secondary Outcomes (5)

• Adverse events

  Adverse event reporting will take place on day 2, 4, 7, 14, 21, then 1, 4 weeks after the last FMT administration.

• Stroop Test

  Before the first administration of FMT (day 0) and one week after the last administration of FMT (day 28)

• 36-Item Short Form Health Survey (SF-36)

  Before the first administration of FMT (day 0) and one week after the last administration of FMT (day 28)

• Ammonia level

  Before the first administration of FMT (day 0) and one week after the last administration of FMT (day 28)

• Microbiome engraftment

  Before the first administration of FMT (day 0), after 3 FMT administrations (day 14), one week after the last administration of FMT (day 28) and 4 weeks after the last administration of FMT.

Study Arms (2)

Fecal Microbiota Transplant (FMT) oral capsules

EXPERIMENTAL

Subjects will receive 15 oral capsules of FMT on days 1, 2, 7, 14, and 21.

Drug: Fecal Microbiota Transplant (FMT) oral capsules

Placebo capsules

PLACEBO COMPARATOR

Subjects will receive placebo capsules on the same schedule as the experimental arm (days 1, 2, 7, 14, and 21).

Drug: Placebo oral capsule

Interventions

Placebo oral capsule DRUG

Oral placebo capsules filled with glycerol and cocoa powder. These capsules are identical in appearance to FMT capsules.

Placebo capsules

Fecal Microbiota Transplant (FMT) oral capsules DRUG

Donors will be healthy individuals, selected through a previously published, rigorous screening process. Elizabeth Hohmann M.D. of MGH has demonstrated the safety and therapeutic efficacy of oral frozen FMT capsules in Clostridium difficile infection, and her lab will produce the capsules for this study.

Fecal Microbiota Transplant (FMT) oral capsules

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of cirrhosis: Based on liver biopsy or clinical assessment of a hepatologist based on history, exam, laboratory and radiographic evidence
• History of at least one episode of overt HE, defined by West Haven Criteria Grades II to IV; episodes of HE that were precipitated by gastrointestinal hemorrhage requiring transfusion of at least 2 units of blood, by medication use, by renal failure requiring dialysis, or by injury to the central nervous system will not be counted as previous HE episodes
• Compliant with lactulose and rifaximin treatment (lactulose: at least one dose at least 5 days per week; rifaximin: at least one dose at least 5 days per week)

You may not qualify if:

• Current episode of overt HE as defined by West Haven Criteria Grades II to IV
• Expectation of liver transplantation within two months of the screening visit
• Current infection
• Variceal bleeding in the last 4 weeks
• Gut-absorbable or intravenous antibiotic therapy (including ciprofloxacin for SBP prophylaxis) in the last 3 months
• Alcohol or illicit drug intake within 3 months, by history and available serum testing; alcohol use will be characterized as \>1 alcoholic drink / month
• PSC as etiology of liver disease, as prior literature has suggested these individuals have a unique microbiome
• History of Roux-en-Y Gastric bypass
• On immunosuppressive medications
• Positive C. difficile test
• Scoring above a threshold cut-off on the Psychometric Hepatic Encephalopathy Score (PHES)
• MELD \> 17
• History of spontaneous bacterial peritonitis
• History of low ascites protein ( ≤ 1g/dL) in the last year
• Hemodialysis in the last 30 days

Sponsors & Collaborators

• Center for Microbiome Informatics and Therapeutics: collaborator
• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (4)

• Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, Kheradman R, Heuman D, Wang J, Gurry T, Williams R, Sikaroodi M, Fuchs M, Alm E, John B, Thacker LR, Riva A, Smith M, Taylor-Robinson SD, Gillevet PM. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology. 2017 Dec;66(6):1727-1738. doi: 10.1002/hep.29306. Epub 2017 Oct 30.

  PMID: 28586116 BACKGROUND

• Youngster I, Mahabamunuge J, Systrom HK, Sauk J, Khalili H, Levin J, Kaplan JL, Hohmann EL. Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. BMC Med. 2016 Sep 9;14(1):134. doi: 10.1186/s12916-016-0680-9.

  PMID: 27609178 BACKGROUND

• Kao D, Roach B, Silva M, Beck P, Rioux K, Kaplan GG, Chang HJ, Coward S, Goodman KJ, Xu H, Madsen K, Mason A, Wong GK, Jovel J, Patterson J, Louie T. Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2017 Nov 28;318(20):1985-1993. doi: 10.1001/jama.2017.17077.

  PMID: 29183074 BACKGROUND

• Bloom PP, Donlan J, Torres Soto M, Daidone M, Hohmann E, Chung RT. Fecal microbiota transplant improves cognition in hepatic encephalopathy and its effect varies by donor and recipient. Hepatol Commun. 2022 Aug;6(8):2079-2089. doi: 10.1002/hep4.1950. Epub 2022 Apr 5.

  PMID: 35384391 DERIVED

MeSH Terms

Conditions

Hepatic Encephalopathy

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Raymond T Chung, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization will be performed by the lab producing the FMT and placebo capsules. Participants, providers, investigators and research assistants will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Associate Proffessor of Gastroenterology

Model Details: This is a two part study. The first part is a 10-patient pilot study, used to find 2 stool donors who precipitate the largest improvement in recipient neurological function and microbiome composition. The second part is a 20-patient RCT, where patients will be randomized to FMT or placebo.

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: February 5, 2018
• Study Start: April 1, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

US (1)