Fecal Microbiota Transplant as Treatment of Hepatic Encephalopathy

Phase

Condition

Arginase Deficiency

Neurologic Disorders

Hepatic Encephalopathy

Treatment

Fecal Microbiota Transplant (FMT) oral capsules

Placebo oral capsule

Clinical Study ID

NCT03420482

2017P002296

Ages 18-75
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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

Exclusion

Exclusion Criteria:

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 SBPprophylaxis) in the last 3 months
Alcohol or illicit drug intake within 3 months, by history and available serumtesting; alcohol use will be characterized as >1 alcoholic drink / month
PSC as etiology of liver disease, as prior literature has suggested theseindividuals 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
Other significant laboratory abnormalities: serum creatinine > 2.0 mg/dL, hemoglobin < 8 g/dL, serum sodium < 125 mmol/L, serum calcium > 11.0 mg/dL, serum potassium < 2.5 mmol/L
Placement of a portosystemic shunt or transjugular intrahepatic portosystemic shunt
Unstable doses of opiates, benzodiazepines or other sedating medication
Unable to provide consent; a. If MMSE is < 18 or the patient is deemed to not havecapacity by an investigator, a legally authorized representative (surrogate) will beallowed to provide consent

Study Design

Fecal Microbiota Transplant (FMT) oral capsules

April 01, 2018

January 31, 2027

Study Description

Decades of investigation demonstrate that hepatic encephalopathy (HE), a common complication of cirrhosis characterized by impaired cognition, develops as a consequence of intestinal microbial products reaching the brain. Recent investigation has found that cirrhotic patients, especially those who have developed HE, have intestinal dysbiosis compared to normal controls. Several plausible mechanisms explain how intestinal dysbiosis could lead to HE. There is limited prior literature on the efficacy of FMT in cirrhosis. The largest documented study of 10 cirrhotic patients receiving a single FMT enema found no significant change in microbiome diversity as assessed by 16S rRNA sequencing. The investigators hypothesize that aggressive manipulation of the microbial composition with fecal microbiota transplant (FMT) will improve neurological function in patients with a history of cirrhosis and HE. The investigators additionally hypothesize that five oral FMT capsule administrations from a previously efficacious stool donor will significantly change the intestinal microbiome composition of a cirrhotic patient. The study will consist of a 10-patient open-label pilot study to identify efficacious stool donors, defined as donors who precipitate the largest improvement in recipient neurological function and microbiome composition. The two most efficacious pilot study stool donors will be selected to donate stool for the randomized controlled trial (RCT). The 20-patient RCT will investigate the effect of FMT on neurological outcomes in patients with cirrhosis and a history of HE. Subjects will be randomized to receive 5 doses of oral FMT capsules or placebo capsules over 21 days. Cognitive testing and stool collections will occur at 4 time points, to assess for changes in neurological function and microbiome composition. The primary outcome is change in neurological function after FMT. The main secondary outcome is change in microbiome composition after FMT. This study could provide valuable information about the ability of FMT to improve intestinal dysbiosis in cirrhosis and treat HE.

Connect with a study center

Massachusetts General Hospital
Boston, Massachusetts 02114
United States
Site Not Available
Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114
United States
Site Not Available

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