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
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. Aim. 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). Aim. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
60
Capsule manufactured without active ingredients.
Probiotic nutritional supplement; Lactobacillus Rhamnosus G
University of Louisville Hospital
Louisville, Kentucky, United States
RECRUITINGBy 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 \[Unit: numerical frequency\]).
Time frame: 180 days
By reducing relapse episodes to minimal/absent incident level
(Unit: incident frequency).
Time frame: 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 \[Unit: numerical frequency\]).
Time frame: 180 days
By lowering a biochemical marker of alcohol intake
PeTH (Unit: μmol/L)
Time frame: 180 days
By significantly improving liver related and clinical markers
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). Clinical 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). Laboratory markers: K18M65 and K18M30 (Unit for both: IU/L).
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Time frame: 180 days
By substantially improving the overall health as assessed by the patient reported outcomes
Quality of Life or QOL scale \[Unit: numerical frequency\], Drinker inventory of consequences or DrInC \[unit: numerical frequency\].
Time frame: 180 days
By lowering frequency and intensity of treatment/disease based adverse effects (AE).
Incident frequency of AE \[Unit: numerical\], Severity Scale (AE/SAE (Unit: 1-5).
Time frame: 180 days