Clinical trial NCT05548452: Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease
Official title: Intestinal Microbiota Transplant in Alcohol-Associated Chronic Liver Disease and Cirrhosis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Liver Disease; Alcohol-Related
Cirrhosis
Alcohol Use Disorder
Keywords: Intestinal Microbiota Transplant
Alcohol Use Disorder
Cirrhosis
Chronic Liver Disease
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2022-09-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to test the safety, tolerability, and effectiveness of the capsules that contain bacteria from healthy individuals when used to treat alcohol craving and drinking.

Detailed description: These intestinal microbiota transplant (IMT) capsules are an investigational drug, which means it has not been approved by the U. S. Food and Drug Administration (FDA). In this study, drug name will be compared to placebo (a look-alike inactive substance, a "sugar pill").

Participants will be randomly assigned (like the flip of a coin) to receive either IMT capsules or placebo capsules. Participants have an equal chance of being assigned to any one of the groups.

In this study, participants will be asked to do the following things:

1. Visit VCU medical center up to 8 times for study visits
2. Take either IMT capsule or the placebo, depending upon which group they are assigned to; these capsules will be given twice on enrollment and after one month
3. Have blood drawn, urine and stool collected at each visit
4. Have testing done to determine the speed of brain function
5. Keep a diary at home
6. Take surveys and answer questions about general health, alcohol craving and consumption and how they are feeling.
7. Give permission for the researchers to collect information about liver disease, alcohol and mental health from medical records.

Participation in this study will last up to 7 months.

Eligibility criteria: Inclusion Criteria:

-\>18 years of age

* Advanced liver disease
* Able to give written, informed consent
* Alcohol as a cause of advanced liver disease
* Continued sustained drinking
* Having previously declined a referral to traditional AUD therapy services or having failed such treatments

Exclusion Criteria:

* Lack of sustained drinking
* Recent or current alcoholic hepatitis
* Alcohol withdrawal symptoms
* Clinically significant use of illicit drugs
* Uncontrolled mood disorders or primary psychotic conditions
* MELD score\>17
* Unclear diagnosis of chronic liver disease
* Current hepatic encephalopathy on lactulose and/or rifaximin
* WBC count\<1000
* Non-elective hospitalization within last month
* on dialysis
* known untreated, in-situ luminal GI cancers
* chronic intrinsic GI diseases (ulcerative colitis, Crohn's disease or microscopic colitis, eosinophilic gastroenteritis and celiac disease)
* Dysphagia within 2 weeks
* History of aspiration, gastroparesis, intestinal obstruction
* Ongoing absorbable antibiotic use
* Severe anaphylactic food allergy
* allergy to ingredients Generally Recognized As Safe in the G3 capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil)
* Adverse event attributable to prior IMT
* ASA Class IV or V
* Pregnant or nursing patients
* acute illness or fever on the day of planned FMT
* Immunosuppression
* Other conditions which make patients are poor candidate for this study per investigator judgement

Primary outcomes:
measure: Number of abstinent days
timeFrame: Baseline to 3 months after treatment (analysis of all 3 primary outcomes via Win Ratio)
measure: Reduction in WHO drinking levels by 1 or greater at month 3
timeFrame: Baseline to 3 months after treatment (analysis of all 3 primary outcomes via Win Ratio)
measure: Phosphatidyl Ethanol (PEth) level change
timeFrame: Baseline to 3 months after treatment (analysis of all 3 primary outcomes via Win Ratio)
Secondary outcomes:
measure: Change in markers of alcohol in urine
timeFrame: Baseline to 3 months after treatment
measure: Change in markers of alcohol in blood
timeFrame: Baseline to 3 months after treatment
measure: Change in percentage of heavy drinking days
timeFrame: Baseline to 3 months after treatment
measure: Change in alcohol craving
timeFrame: Baseline to 3 months after treatment
measure: Change in life problems
timeFrame: Baseline to 3 months after treatment
measure: Number of hospitalizations
timeFrame: 6 months
measure: Number of serious adverse events
timeFrame: 6 months
measure: Change in microbial composition
timeFrame: Baseline to 3 months after treatment
measure: Change in liver function
timeFrame: Baseline to 3 months after treatment
measure: Change in Psychometric hepatic encephalopathy score (PHES)
timeFrame: Baseline to 3 months after treatment
measure: Change in EncephalApp Stroop Test
timeFrame: Baseline to 3 months after treatment
measure: Change in health related quality of live (HRQOL)
timeFrame: Baseline to 3 months after treatment
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Jasmohan S Bajaj, MD
role: PRINCIPAL_INVESTIGATOR
References: