Fecal Microbial Transplant for Alcohol Misuse in Cirrhosis

NCT ID: NCT03416751

Last Updated: 2020-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-01
• Study Completion Date: 2020-04-10

Brief Summary

There is an epidemic of alcohol use disorder in the US. Alcoholism is an epidemic that spans all ages and socio-economic strata, which has a major impact on healthcare expenditure. Alcohol-associated liver disease can take the form of mild fatty liver, chronic liver disease including cirrhosis and a very acute active form known as alcoholic hepatitis. However, most patients with alcohol abuse issues with cirrhosis do not develop alcoholic hepatitis and are not willing to quit drinking. These patients are neither liver transplant candidates due to their drinking nor have any recourse to therapies directed towards the liver as is the case with alcoholic hepatitis. This is very large proportion of cirrhotic patients who do not have many therapeutic options.

Prior studies have demonstrated that these patients have an altered gut-liver axis which is exacerbated by dysbiosis and a higher production of potentially toxic secondary bile acids. These secondary bile acids in turn have the potential to worsen the already impaired gut barrier in these patients, creating a vicious cycle of inflammation and further liver injury that is led by the altered microbial composition. A gut-based strategy that has the capability of "resetting" this dysbiosis could help in the amelioration of this inflammatory load and improve the prognosis of these patients.

Detailed Description

Randomized, single-blind, placebo-controlled safety, tolerability study with exploratory endpoints and pathophysiological evaluation of the FMT

Two groups of outpatients with cirrhosis will be randomized using random sequence generator into no-treatment and FMT groups.

Once patients are randomized 1:1 into group 1 (FMT) and group 2 (Placebo), both will be followed over 31 days and will include a 6 month visit to collect samples, perform questionnaires and to assess SAEs.

There is an epidemic of alcohol use disorder in the US. Alcoholism is an epidemic that spans all ages and socio-economic strata, which has a major impact on healthcare expenditure. Alcohol-associated liver disease can take the form of mild fatty liver, chronic liver disease including cirrhosis and a very acute active form known as alcoholic hepatitis. However, most patients with alcohol abuse issues with cirrhosis do not develop alcoholic hepatitis and are not willing to quit drinking. These patients are neither liver transplant candidates due to their drinking nor have any recourse to therapies directed towards the liver as is the case with alcoholic hepatitis. This is very large proportion of cirrhotic patients who do not have many therapeutic options.

Prior studies have demonstrated that these patients have an altered gut-liver axis which is exacerbated by dysbiosis and a higher production of potentially toxic secondary bile acids. These secondary bile acids in turn have the potential to worsen the already impaired gut barrier in these patients, creating a vicious cycle of inflammation and further liver injury that is led by the altered microbial composition. The investigators believe that a gut-based strategy that has the capability of "resetting" this dysbiosis can help in the amelioration of this inflammatory load and improve the prognosis of these patients.

Conditions

Cirrhosis; Alcohol Abuse

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Fecal Microbial transplantation

Patients will get one-dose of 90ml of FMT enema on day 1 that has been received from OpenBiome using a rational donor

Group Type: EXPERIMENTAL

Fecal Microbial Transplant

Intervention Type: BIOLOGICAL

Fecal transplant from a donor in the OpenBiome Registry

Placebo

Patients will get one-dose of 90ml of saline enema on day 1

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo enemas

Interventions

Fecal Microbial Transplant

Fecal transplant from a donor in the OpenBiome Registry

Intervention Type: BIOLOGICAL

Placebo

Placebo enemas

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

A. Cirrhosis diagnosed by any of the following in a patient with chronic liver disease:

1. Liver Biopsy

2. Radiologic evidence of varices, cirrhosis or portal hypertension

3. Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1

4. Endoscopic evidence of varices or portal gastropathy

5. Fibroscan B. Age between 21 and 75 C. Able to give written, informed consent (demonstrated by mini-mental status exam>25 at the time of consenting) D. Subject must have alcohol as a cause of cirrhosis

i. Continued sustained drinking pattern with AUDIT score ≥8 in the last month and fulfilling DSM-V criteria for alcohol misuse ii. Unable or unwilling to get mental health attention to quit alcohol (at least 3-months period of referrals to Substance abuse programs or other alcohol treatment approaches) iii. Adult companion who can accompany patient and provide insight into alcohol drinking patterns

Exclusion Criteria

A. MELD score >17 B. Child Class C C. WBC count <1000 cells/mm3 D. Platelet count<50,000/mm3 E. TIPS in place for less than a month F. HE episode within a month prior to the study G. Currently on absorbable antibiotics H. Infection at the time of the FMT (diagnosed by blood culture positivity, urinalysis, paracentesis as needed) I. Patients who are aged >75 years J. Patients who are pregnant or nursing (will be checked using a urine pregnancy test) K. Patients who are incarcerated L. Patients who are incapable of giving their own informed consent

M. Patients who are immuno-compromised due to the following reasons:

1. HIV infection (any CD4 count)

2. Inherited/primary immune disorders

3. Current or recent (<3 months) treatment with anti-neoplastic agent

4. Current or recent (<3 months) treatment with any immunosuppressant medications [including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil]. Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll.

N. Patients with a history of severe (anaphylactic) food allergy O. Patients who have previously undergone FMT P. Patients on renal replacement therapy Q. Patients who are unwilling or unable to hold the enemas R. Patients with untreated, in-situ colorectal cancer S. Patients with a history of chronic intrinsic GI diseases such as inflammatory bowel disease (ulcerative colitis, Crohn's disease or microscopic colitis), eosinophilic gastroenteritis, celiac disease or irritable bowel syndrome T. Major gastro-intestinal or intra-abdominal surgery in the last three months U. Unable to comply with protocol requirements V. Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V W. Patients with acute illness or fever on the day of planned FMT will be excluded with the option of including that subject at a future date X. Any conditions for which, in opinion of MD, the treatment may pose a health risk Y. Grade 2-4 or complicated hemorrhoids

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OpenBiome

INDUSTRY

Sponsor Role: collaborator

Hunter Holmes Mcguire Veteran Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jasmohan S Bajaj, MD

Role: PRINCIPAL_INVESTIGATOR

Hunter Holmes McGuire VA Medical Center

Locations

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, United States

Countries

United States

Other Identifiers

BAJAJ0021A

Identifier Type: -

Identifier Source: org_study_id