LGG Supplementation in Patients With AUD and ALD

NCT05178069 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 21.1038K23AA029198
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

To test the efficacy of 6-month LGG compared to placebo in treating Alcoholic Use Disorder (AUD) and liver injury in Alcoholic Hepatitis (AH). And to evaluate the effects of LGG treatment compared to placebo on therapeutic-mechanistic markers of the gut-brain axis and pro-inflammatory activity in patients with AUD and moderate AH

Conditions

Alcohol Use Disorder; Alcohol-associated Liver Disease

Keywords

AUD; ALD; AH; TLFB; LTDH; AUDIT; WHO Drinking Level Reduction Criteria; MELD; ALT; AST; ABIC; Total Bilirubin; Heavy Drinking; Drinking Pattern; AUD Domains; Albumin

Outcome Measures

Primary Outcomes (4)

• By lowering heavy drinking to meet the criteria on the responder definitions of abstinence, no heavy drinking days, WHO 1-level, and WHO 2-level reduction

  Timeline Followback for past 180 days \[Unit: numerical frequency\], AUDIT \[Unit: numerical frequency\], monthly drinking questionnaire \[Unit: numerical frequency\]).

  180 days

• By reducing relapse episodes to minimal/absent incident level

  (Unit: incident frequency).

  180 days

• By showing a significant positive effect on one or more of the underlying neurobehavioral domains.

  Questionnaires: reward (reasons for heavy drinking questionnaire or RHDQ \[Unit: numerical frequency\]), craving (Penn Alcohol Craving Scale or PACS, \[Unit: numerical frequency\]; and obsessive compulsive drinking scale or OCDS \[Unit: numerical frequency\]), withdrawal (Clinical Institute Withdrawal Assessment Alcohol Scale Revised \[CIWA-AR\] or CIWA-AR \[Unit: numerical frequency\]), and reinforcement effects (Desires for Alcohol Questionnaire or DAQ \[Unit: numerical frequency\]).

  180 days

• By lowering a biochemical marker of alcohol intake

  PeTH (Unit: μmol/L)

  180 days

Secondary Outcomes (3)

• By significantly improving liver related and clinical markers

  180 days

• By substantially improving the overall health as assessed by the patient reported outcomes

  180 days

• By lowering frequency and intensity of treatment/disease based adverse effects (AE).

  180 days

Other Outcomes (1)

• To determine the therapeutic-mechanistic markers of gut-brain axis, pro-inflammatory activity in AUD

  180 days

Study Arms (2)

Placebo Comparator: Placebo for Probiotic

PLACEBO COMPARATOR

Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.

Drug: : Placebo for Probiotic

Active Comparator: Lactobacillus Rhamnosus GG

ACTIVE COMPARATOR

Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.

Dietary Supplement: Lactobacillus Rhamnosus GG

Interventions

: Placebo for Probiotic DRUG

Capsule manufactured without active ingredients.

Also known as: Dummy capsule

Placebo Comparator: Placebo for Probiotic

Lactobacillus Rhamnosus GG DIETARY_SUPPLEMENT

Probiotic nutritional supplement; Lactobacillus Rhamnosus G

Also known as: Culturelle

Active Comparator: Lactobacillus Rhamnosus GG

Eligibility Criteria

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

You may qualify if:

• Breath alcohol concentration (BAC) equal to 0.00 when the participant signs the informed consent document.
• Age between 21 and 65 years old (inclusive).
• Willingness to receive trial treatment.
• Ability to provide informed consent
• Understanding that this is not an alcohol treatment study.
• Heavy drinking. Men must consume ≥ 20 and women ≥ 14 standardized alcoholic beverages a week for the past 3 months.
• Diagnosis of Alcohol Use Disorder using DSM V criteria.
• \<AST\<400 U/L; AST \> ALT; and ALT \< 200 U/L; total bilirubin \> 1.2 mg/dL
• Model for End-Stage Liver Disease: 8 ≤ (MELD) ≤19.
• Good health as confirmed by medical history, physical examination, ECG, laboratory tests and vital signs except for liver injury and AUD related history.
• Provide contact information for someone who may be able to contact the subject in case of a missed appointment.
• Females of child-bearing potential must not be pregnant and must be using birth control

You may not qualify if:

• Current (last 12 months) DSM V diagnosis of dependence on any psychoactive substance other than alcohol or nicotine,
• Positive urine drug screen at baseline for any illegal substance other than marijuana,
• History of hospitalization for alcohol intoxication delirium, alcohol withdrawal delirium or seizure,
• Participation in any research study for alcoholism treatment within 3 months prior to signing the informed consent,
• Pharmacological treatment with naltrexone, acamprosate, topiramate, or disulfiram within 1 month prior to randomization,
• Lifetime diagnosis based on DSM-V criteria of schizophrenia, bipolar disorder, or other psychosis, eating disorders; current or past year diagnosis of major depression
• In the investigators' opinion, moderate to severe risk of suicide (e.g., active plan, or recent attempt in last 6 months),
• Current use of psychotropic medications that cannot be discontinued,
• Clinically significant medical abnormalities (apart from moderate ALD, MELD≤19),
• Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) \>10, at screening for more than 3 days,
• Serious medical diseases, such as cancer, liver cirrhosis, pancreatitis, severe alcohol associated hepatitis, heart chronic failure, chronic kidney failure, chronic intestinal diseases (e.g., Crohn's disease), chronic neurological disorders (e.g., tardive dyskinesia, epilepsy, Parkinson's disease)
• History of clinically significant hypotension (e.g., history of lipotimia and/or syncopal episodes)
• History of adverse reactions to needle puncture,
• Obesity (BMI ≥ 33.0 kg/m2),
• Pregnancy; incarceration; inability to provide consent

Sponsors & Collaborators

• University of Louisville: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

University of Louisville Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

Related Publications (8)

• McClain CJ, Vatsalya V, Mitchell MC. Keratin-18: Diagnostic, Prognostic, and Theragnostic for Alcohol-Associated Hepatitis. Am J Gastroenterol. 2021 Jan 1;116(1):77-79. doi: 10.14309/ajg.0000000000001042.

  PMID: 33306505 BACKGROUND

• Gala KS, Vatsalya V. Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope. Cells. 2020 Feb 25;9(3):524. doi: 10.3390/cells9030524.

  PMID: 32106390 BACKGROUND

• Vatsalya V, Cave MC, Kong M, Gobejishvili L, Falkner KC, Craycroft J, Mitchell M, Szabo G, McCullough A, Dasarathy S, Radaeva S, Barton B, McClain CJ. Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis. Clin Gastroenterol Hepatol. 2020 Aug;18(9):2046-2054. doi: 10.1016/j.cgh.2019.11.050. Epub 2019 Dec 4.

  PMID: 31811953 BACKGROUND

• Zhou Y, Vatsalya V, Gobejishvili L, Lamont RJ, McClain CJ, Feng W. Porphyromonas gingivalis as a Possible Risk Factor in the Development/Severity of Acute Alcoholic Hepatitis. Hepatol Commun. 2018 Dec 14;3(2):293-304. doi: 10.1002/hep4.1296. eCollection 2019 Feb.

  PMID: 30766965 BACKGROUND

• Gowin JL, Sloan ME, Stangl BL, Vatsalya V, Ramchandani VA. Vulnerability for Alcohol Use Disorder and Rate of Alcohol Consumption. Am J Psychiatry. 2017 Nov 1;174(11):1094-1101. doi: 10.1176/appi.ajp.2017.16101180. Epub 2017 Aug 4.

  PMID: 28774194 BACKGROUND

• Vatsalya V, Gowin JL, Schwandt ML, Momenan R, Coe MA, Cooke ME, Hommer DW, Bartlett S, Heilig M, Ramchandani VA. Effects of Varenicline on Neural Correlates of Alcohol Salience in Heavy Drinkers. Int J Neuropsychopharmacol. 2015 Jul 25;18(12):pyv068. doi: 10.1093/ijnp/pyv068.

  PMID: 26209857 BACKGROUND

• Vatsalya V, Gala KS, Hassan AZ, Frimodig J, Kong M, Sinha N, Schwandt ML. Characterization of Early-Stage Alcoholic Liver Disease with Hyperhomocysteinemia and Gut Dysfunction and Associated Immune Response in Alcohol Use Disorder Patients. Biomedicines. 2020 Dec 24;9(1):7. doi: 10.3390/biomedicines9010007.

  PMID: 33374263 BACKGROUND

• Vatsalya V, Kong M, Marsano LM, Kurlawala Z, Chandras KV, Schwandt ML, Ramchandani VA, McClain CJ. Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients. Subst Abuse. 2020 Sep 9;14:1178221820955185. doi: 10.1177/1178221820955185. eCollection 2020.

  PMID: 32963470 BACKGROUND

Related Links

• Details of the Study at NIH Reporter
• Clinical Laboratory for the Intervention Development of AUD and Organ-Injury

MeSH Terms

Conditions

Alcoholism

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Vatsalya Vatsalya, MD

  Department of Medicine, University of Louisville

  PRINCIPAL INVESTIGATOR

• Craig J McClain, MD

  Department of Medicine, University of Louisville

  STUDY CHAIR

• Harsh Tiwari, MD

  University of Louisville

  STUDY DIRECTOR

Central Study Contacts

Amber Jackson, BS CCRP

CONTACT

502-852-2905; amber.jackson.1@louisville.edu

Steve Mahanes

CONTACT

502-852-1388; steve.mahanes@louisville.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Faculty in Medicine

Model Details: Time by Treatment

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: January 5, 2022
• Study Start: June 1, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)