Fecal Microbial Transplant for Alcohol Misuse in Cirrhosis

NCT03416751 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BAJAJ0021A
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Cirrhosis; Alcohol Abuse

Outcome Measures

Primary Outcomes (3)

• Proportion of participants with a related serious adverse event

  Related SAE to FMT

  15 days

• Proportion of participants with newly acquired transmissible infectious diseases

  Related transmissible infectious disease to FMT

  15 days

• Proportion of participants with a related adverse event

  Related adverse event that does not meet the criteria for a serious adverse event

  15 days

Secondary Outcomes (10)

• Proportion of participants with a related serious adverse event

  30 days and 6 months

• Proportion of participants with a related adverse event

  30 days and 6 months

• Proportion of participants with newly acquired transmissible infectious diseases

  30 days and 6 months

• Composition of microbial change

  day 15 post-intervention

• AUDIT questionnaire

  day 15 post-intervention

Study Arms (2)

Fecal Microbial transplantation

EXPERIMENTAL

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

Biological: Fecal Microbial Transplant

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Fecal Microbial Transplant BIOLOGICAL

Fecal transplant from a donor in the OpenBiome Registry

Fecal Microbial transplantation

Placebo OTHER

Placebo enemas

Placebo

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Cirrhosis diagnosed by any of the following in a patient with chronic liver disease:
• Liver Biopsy
• Radiologic evidence of varices, cirrhosis or portal hypertension
• Laboratory evidence of platelet count \<100,000 or AST/ALT ratio\>1
• Endoscopic evidence of varices or portal gastropathy
• 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

You may not qualify if:

• 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:
• HIV infection (any CD4 count)
• Inherited/primary immune disorders
• Current or recent (\<3 months) treatment with anti-neoplastic agent
• 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

Sponsors & Collaborators

• Hunter Holmes Mcguire Veteran Affairs Medical Center: lead
• OpenBiome: collaborator

Study Sites (1)

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249, United States

Location

MeSH Terms

Conditions

Fibrosis; Alcoholism

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Jasmohan S Bajaj, MD

  Hunter Holmes McGuire VA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: January 31, 2018
• Study Start: February 1, 2018
• Primary Completion: April 10, 2020
• Study Completion: April 10, 2020
• Last Updated: July 28, 2020

Record last verified: 2020-07

Locations

US (1)