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Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease

Phase 1
Recruiting
Conditions
Liver Disease; Alcohol-Related
Cirrhosis
Alcohol Use Disorder
Interventions
Drug: Placebo Capsules
Drug: Intestinal Microbiota Transplant (IMT) Capsules
Registration Number
NCT05548452
Lead Sponsor
Virginia Commonwealth University
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
80
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo capsulesPlacebo CapsulesCapsules will be provided twice during the trial
Intestinal Microbiota Transplant capsulesIntestinal Microbiota Transplant (IMT) CapsulesCapsules will be provided twice during the trial
Primary Outcome Measures
NameTimeMethod
Number of abstinent daysBaseline to 3 months after treatment (analysis of all 3 primary outcomes via Win Ratio)

Number of drinks per day will be measured through self report

Reduction in WHO drinking levels by 1 or greater at month 3Baseline to 3 months after treatment (analysis of all 3 primary outcomes via Win Ratio)

WHO grade by self report

Phosphatidyl Ethanol (PEth) level changeBaseline to 3 months after treatment (analysis of all 3 primary outcomes via Win Ratio)

Change to \<70

Secondary Outcome Measures
NameTimeMethod
Change in alcohol cravingBaseline to 3 months after treatment

The Alcohol Craving Questionnaire is a 12-item instrument

Number of hospitalizations6 months

All hospitalizations and liver-related hospitalizations will be tracked

Number of serious adverse events6 months

All serious adverse events and intervention related adverse events will be tracked

Change in microbial compositionBaseline to 3 months after treatment

Percentage of beneficial intestinal bacteria will be assessed by genetic analysis of stool samples.

Change in health related quality of live (HRQOL)Baseline to 3 months after treatment

HRQOL will be assessed using the Sickness Impact Profile

Change in percentage of heavy drinking daysBaseline to 3 months after treatment

Self reported drinking behavior will be used to calculate percentage of heavy drinking days

Change in life problemsBaseline to 3 months after treatment

The Short Index of Problems is a 15-item instrument which measures medical, psychological, social, occupational, and legal problems.

Change in Psychometric hepatic encephalopathy score (PHES)Baseline to 3 months after treatment

Brain function will be assessed using the PHES

Change in EncephalApp Stroop TestBaseline to 3 months after treatment

Brain function will be assessed using the EncephalApp Stroop Test

Change in markers of alcohol in bloodBaseline to 3 months after treatment

Blood samples will be analyzed for Phosphatidyl Ethanol (PEth)

Change in liver functionBaseline to 3 months after treatment

The Model for end-stage liver disease (MELD) score will be used to asses changes in liver function.

Change in markers of alcohol in urineBaseline to 3 months after treatment

Urine samples will be analyzed for levels of Ethyl Glucuronide (EtG) and Ethyl Sulfate (EtS)

Trial Locations

Locations (2)

Virginia Commonwealth University

🇺🇸

Richmond, Virginia, United States

Hunter Holmes McGuire VA Medical Center

🇺🇸

Richmond, Virginia, United States

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