Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease

Study Overview
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Brief Summary
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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
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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: Visit VCU medical center up to 8 times for study visits 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 Have blood drawn, urine and stool collected at each visit Have testing done to determine the speed of brain function Keep a diary at home Take surveys and answer questions about general health, alcohol craving and consumption and how they are feeling. 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.

Official Title
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Intestinal Microbiota Transplant in Alcohol-Associated Chronic Liver Disease and Cirrhosis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Conditions
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Liver Disease; Alcohol-Related, Cirrhosis, Alcohol Use Disorder

Intervention / Treatment
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* Drug: Intestinal Microbiota Transplant (IMT) Capsules
* Drug: Placebo Capsules


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intestinal Microbiota Transplant capsules<br>Capsules will be provided twice during the trial | Drug: Intestinal Microbiota Transplant (IMT) Capsules<br>* Capsules containing freeze-dried intestinal microbiota from healthy human donors<br>|
| Placebo Comparator: Placebo capsules<br>Capsules will be provided twice during the trial | Drug: Placebo Capsules<br>* Capsules containing an inactive substance (sugar pill)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alcohol consumption | Number of drinks per day will be measured through self report | Baseline to 3 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in markers of alcohol in urine | Urine samples will be analyzed for levels of Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS) | Baseline to 3 months after treatment | 
| Change in markers of alcohol in blood | Blood samples will be analyzed for Phosphatidyl Ethanol (PEth) | Baseline to 3 months after treatment | 
| Change in percentage of heavy drinking days | Self reported drinking behavior will be used to calculate percentage of heavy drinking days | Baseline to 3 months after treatment | 
| Change in alcohol craving | The Alcohol Craving Questionnaire is a 12-item instrument | Baseline to 3 months after treatment | 
| Change in life problems | The Short Index of Problems is a 15-item instrument which measures medical, psychological, social, occupational, and legal problems. | Baseline to 3 months after treatment | 
| Number of hospitalizations | All hospitalizations and liver-related hospitalizations will be tracked | 6 months | 
| Number of serious adverse events | All serious adverse events and intervention related adverse events will be tracked | 6 months | 
| Change in microbial composition | Percentage of beneficial intestinal bacteria will be assessed by genetic analysis of stool samples. | Baseline to 3 months after treatment | 
| Change in liver function | The Model for end-stage liver disease (MELD) score will be used to asses changes in liver function. | Baseline to 3 months after treatment | 
| Change in Psychometric hepatic encephalopathy score (PHES) | Brain function will be assessed using the PHES | Baseline to 3 months after treatment | 
| Change in EncephalApp Stroop Test | Brain function will be assessed using the EncephalApp Stroop Test | Baseline to 3 months after treatment | 
| Change in health related quality of live (HRQOL) | HRQOL will be assessed using the Sickness Impact Profile | Baseline to 3 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intestinal Microbiota Transplant, Alcohol Use Disorder, Cirrhosis, Chronic Liver Disease