Ignite Creation Date:
2025-12-24 @ 11:00 PM
Ignite Modification Date:
2025-12-25 @ 8:29 PM
Study NCT ID:
NCT05178069
Status:
RECRUITING
Last Update Posted:
2025-10-31
First Post:
2021-11-09
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
LGG Supplementation in Patients With AUD and ALD
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000437', 'term': 'Alcoholism'}], 'ancestors': [{'id': 'D019973', 'term': 'Alcohol-Related Disorders'}, {'id': 'D019966', 'term': 'Substance-Related Disorders'}, {'id': 'D064419', 'term': 'Chemically-Induced Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D019936', 'term': 'Probiotics'}], 'ancestors': [{'id': 'D019587', 'term': 'Dietary Supplements'}, {'id': 'D005502', 'term': 'Food'}, {'id': 'D000066888', 'term': 'Diet, Food, and Nutrition'}, {'id': 'D010829', 'term': 'Physiological Phenomena'}, {'id': 'D019602', 'term': 'Food and Beverages'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Time by Treatment'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 60}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-06-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-10', 'completionDateStruct': {'date': '2027-02-28', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-10-29', 'studyFirstSubmitDate': '2021-11-09', 'studyFirstSubmitQcDate': '2021-12-15', 'lastUpdatePostDateStruct': {'date': '2025-10-31', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2022-01-05', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-08-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'To determine the therapeutic-mechanistic markers of gut-brain axis, pro-inflammatory activity in AUD', 'timeFrame': '180 days', 'description': '1. By identifying the blood biomarkers of gut-barrier dysfunction and endotoxemia as assessed by: LPS \\[Unit: EU/ml\\], LBP \\[Unit: ng/ml\\], sCD14 \\[Unit: x 10\\^6 pg/ml\\]. Serum Inflammation markers: IL1β, IL33, IL18, IL17, IL22, TNFα \\[Units for all: pg/ml\\].\n2. By determining the therapeutic targets of LGG involved in the gut-brain axis of AUD using LC-MS metabolomic fecal assays (candidate markers of gut-dysfunction associated neurotransmitters): Gamma Aminobutyric Acid or GABA \\[Unit: pmoles/ml\\], hexyl-2-methyl butyrate or HMBA (Unit: mmol/L), serotonin (Unit: ng/mL), dopamine (Unit: ng/ml), acetylcholine (Unit: nmol/L), tryptophan (Unit: umol/L), and short-chain fatty acids (Unit: mmol/L). Units can be relative in intensity (as fold-change).\n3. By validating the efficacy of LGG treatment vs. placebo to lower inflammation using an ex-vivo design: Candidate WBC type derived Inflammation markers: IL1β, IL33, IL18, IL17, IL22, TNFα \\[Units for all: pg/ml\\].'}], 'primaryOutcomes': [{'measure': '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', 'timeFrame': '180 days', 'description': 'Timeline Followback for past 180 days \\[Unit: numerical frequency\\], AUDIT \\[Unit: numerical frequency\\], monthly drinking questionnaire \\[Unit: numerical frequency\\]).'}, {'measure': 'By reducing relapse episodes to minimal/absent incident level', 'timeFrame': '180 days', 'description': '(Unit: incident frequency).'}, {'measure': 'By showing a significant positive effect on one or more of the underlying neurobehavioral domains.', 'timeFrame': '180 days', 'description': '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\\]).'}, {'measure': 'By lowering a biochemical marker of alcohol intake', 'timeFrame': '180 days', 'description': 'PeTH (Unit: μmol/L)'}], 'secondaryOutcomes': [{'measure': 'By significantly improving liver related and clinical markers', 'timeFrame': '180 days', 'description': "Liver markers: Aspartate transaminases or AST (Unit: IU/L), Alanine Transaminases or ALT (Unit: IU/L), Albumin (Unit: g/dL), Total bilirubin (Unit: mg/dL), Creatinine (Unit: mg/dL), and INR (Unit: numerical), AST:ALT ratio (numerical unit), Prothrombin Time or PT (Unit: seconds).\n\nClinical marker: Model For End-Stage Liver Disease or MELD (\\[=0.957 × ln(Cr) + 0.378 × ln(bilirubin) + 1.120 × ln(INR) + 0.643\\]. Unit: numerical), Maddrey's Discriminant Function for Alcoholic Hepatitis or Maddrey DF (\\[=4.6 \\* (Pt's PT - Control PT) + TBili\\]. Unit: numerical).\n\nLaboratory markers: K18M65 and K18M30 (Unit for both: IU/L)."}, {'measure': 'By substantially improving the overall health as assessed by the patient reported outcomes', 'timeFrame': '180 days', 'description': 'Quality of Life or QOL scale \\[Unit: numerical frequency\\], Drinker inventory of consequences or DrInC \\[unit: numerical frequency\\].'}, {'measure': 'By lowering frequency and intensity of treatment/disease based adverse effects (AE).', 'timeFrame': '180 days', 'description': 'Incident frequency of AE \\[Unit: numerical\\], Severity Scale (AE/SAE (Unit: 1-5).'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'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'], 'conditions': ['Alcohol Use Disorder', 'Alcohol-associated Liver Disease']}, 'referencesModule': {'references': [{'pmid': '33306505', 'type': 'BACKGROUND', 'citation': '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': '32106390', 'type': 'BACKGROUND', 'citation': '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': '31811953', 'type': 'BACKGROUND', 'citation': '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': '30766965', 'type': 'BACKGROUND', 'citation': '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': '28774194', 'type': 'BACKGROUND', 'citation': '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': '26209857', 'type': 'BACKGROUND', 'citation': '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': '33374263', 'type': 'BACKGROUND', 'citation': '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': '32963470', 'type': 'BACKGROUND', 'citation': '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.'}], 'seeAlsoLinks': [{'url': 'https://reporter.nih.gov/search/zmJAfR_IOkGNjlHYcbLx0w/project-details/10191836', 'label': 'Details of the Study at NIH Reporter'}, {'url': 'https://louisville.edu/medicine/departments/medicine/divisions/gimedicine/faculty/vatsalya-lab', 'label': 'Clinical Laboratory for the Intervention Development of AUD and Organ-Injury'}]}, 'descriptionModule': {'briefSummary': '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', 'detailedDescription': 'Aim. 1: To test the efficacy of 6-month LGG compared to placebo in treating AUD: (1a) by lowering heavy drinking (1b) by reducing relapse episodes to minimal/absent incident level; (1c) by showing a significant positive effect on one or more of the underlying neurobehavioral domain, and (1d) by lowering a biochemical marker of alcohol intake.\n\nAim. 2: To test if 6-month LGG treatment compared to placebo will improve the symptoms and liver injury in AH: (2a) by significantly improving liver related tests (AST, ALT, AST:ALT, albumin, bilirubin and INR; K18M65 and K18M30) and clinical severity/prognostic markers (MELD, Maddrey); (2b) by substantially improving the overall health as assessed by the patient reported outcomes (Quality of Life \\[QOL\\] scale, and drinker inventory of consequences \\[DrInC\\]); and (2c) by lowering frequency and intensity of treatment/disease based adverse effects (AE).\n\nAim. 3: To evaluate the effects of LGG treatment compared to placebo on therapeutic-mechanistic markers of gut-brain axis and pro-inflammatory activity in patients with AUD and moderate AH: (3a) by identifying the blood biomarkers of gut-barrier dysfunction and endotoxemia, and inflammation; (3b) by determining the therapeutic targets of LGG involved in the gut-brain axis of AUD using LC-MS metabolomic fecal assays (candidate markers of gut-dysfunction associated neurotransmitters); and (3c) by validating the efficacy of LGG treatment vs. placebo to lower inflammation using an ex-vivo design.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Breath alcohol concentration (BAC) equal to 0.00 when the participant signs the informed consent document.\n2. Age between 21 and 65 years old (inclusive).\n3. Willingness to receive trial treatment.\n4. Ability to provide informed consent\n5. Understanding that this is not an alcohol treatment study.\n6. Heavy drinking. Men must consume ≥ 20 and women ≥ 14 standardized alcoholic beverages a week for the past 3 months.\n7. Diagnosis of Alcohol Use Disorder using DSM V criteria.\n8. 50 \\<AST\\<400 U/L; AST \\> ALT; and ALT \\< 200 U/L; total bilirubin \\> 1.2 mg/dL\n9. Model for End-Stage Liver Disease: 8 ≤ (MELD) ≤19.\n10. Good health as confirmed by medical history, physical examination, ECG, laboratory tests and vital signs except for liver injury and AUD related history.\n11. Provide contact information for someone who may be able to contact the subject in case of a missed appointment.\n12. . Females of child-bearing potential must not be pregnant and must be using birth control\n\nExclusion Criteria:\n\n1. Current (last 12 months) DSM V diagnosis of dependence on any psychoactive substance other than alcohol or nicotine,\n2. Positive urine drug screen at baseline for any illegal substance other than marijuana,\n3. History of hospitalization for alcohol intoxication delirium, alcohol withdrawal delirium or seizure,\n4. Participation in any research study for alcoholism treatment within 3 months prior to signing the informed consent,\n5. Pharmacological treatment with naltrexone, acamprosate, topiramate, or disulfiram within 1 month prior to randomization,\n6. Lifetime diagnosis based on DSM-V criteria of schizophrenia, bipolar disorder, or other psychosis, eating disorders; current or past year diagnosis of major depression\n7. In the investigators' opinion, moderate to severe risk of suicide (e.g., active plan, or recent attempt in last 6 months),\n8. Current use of psychotropic medications that cannot be discontinued,\n9. Clinically significant medical abnormalities (apart from moderate ALD, MELD≤19),\n10. Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) \\>10, at screening for more than 3 days,\n11. 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)\n12. History of clinically significant hypotension (e.g., history of lipotimia and/or syncopal episodes)\n13. History of adverse reactions to needle puncture,\n14. Obesity (BMI ≥ 33.0 kg/m2),\n15. Pregnancy; incarceration; inability to provide consent\n16. Signs of systemic infection: Fever \\> 38o C, positive blood or ascites cultures, on appropriate antibiotic therapy for \\> 3 days within 3 days of inclusion\n17. Acute gastrointestinal bleeding requiring \\> 2 units blood transfusion within the previous 2 weeks\n18. Undue risk from immunosuppression: Positive HBsAg; positive skin PPD skin test or history of treatment for tuberculosis; known HIV infection"}, 'identificationModule': {'nctId': 'NCT05178069', 'acronym': 'AUD+ALD', 'briefTitle': 'LGG Supplementation in Patients With AUD and ALD', 'organization': {'class': 'OTHER', 'fullName': 'University of Louisville'}, 'officialTitle': 'Lactobacillus Rhamnosus GG: A Novel Probiotic Therapy for Treating Alcohol Use Disorder', 'orgStudyIdInfo': {'id': '21.1038'}, 'secondaryIdInfos': [{'id': 'K23AA029198', 'link': 'https://reporter.nih.gov/quickSearch/K23AA029198', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo Comparator: Placebo for Probiotic', 'description': 'Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.', 'interventionNames': ['Drug: : Placebo for Probiotic']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Active Comparator: Lactobacillus Rhamnosus GG', 'description': 'Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.', 'interventionNames': ['Dietary Supplement: Lactobacillus Rhamnosus GG']}], 'interventions': [{'name': ': Placebo for Probiotic', 'type': 'DRUG', 'otherNames': ['Dummy capsule'], 'description': 'Capsule manufactured without active ingredients.', 'armGroupLabels': ['Placebo Comparator: Placebo for Probiotic']}, {'name': 'Lactobacillus Rhamnosus GG', 'type': 'DIETARY_SUPPLEMENT', 'otherNames': ['Culturelle'], 'description': 'Probiotic nutritional supplement; Lactobacillus Rhamnosus G', 'armGroupLabels': ['Active Comparator: Lactobacillus Rhamnosus GG']}]}, 'contactsLocationsModule': {'locations': [{'zip': '40202', 'city': 'Louisville', 'state': 'Kentucky', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Vatsalya Vatsalya, MD, PgD, MSc, MS, FRSM', 'role': 'CONTACT', 'email': 'v0vats01@louisville.edu', 'phone': '502-952-8928'}, {'name': 'Steve Mahanes', 'role': 'CONTACT', 'email': 'steve.mahanes@louisville.edu', 'phone': '5028521388'}], 'facility': 'University of Louisville Hospital', 'geoPoint': {'lat': 38.25424, 'lon': -85.75941}}], 'centralContacts': [{'name': 'Amber Jackson, BS CCRP', 'role': 'CONTACT', 'email': 'amber.jackson.1@louisville.edu', 'phone': '502-852-2905'}, {'name': 'Steve Mahanes', 'role': 'CONTACT', 'email': 'steve.mahanes@louisville.edu', 'phone': '502-852-1388'}], 'overallOfficials': [{'name': 'Vatsalya Vatsalya, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Medicine, University of Louisville'}, {'name': 'Craig J McClain, MD', 'role': 'STUDY_CHAIR', 'affiliation': 'Department of Medicine, University of Louisville'}, {'name': 'Harsh Tiwari, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'University of Louisville'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Louisville', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute on Alcohol Abuse and Alcoholism (NIAAA)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Faculty in Medicine', 'investigatorFullName': 'Vatsalya Vatsalya', 'investigatorAffiliation': 'University of Louisville'}}}}