Probiotic LGG for Alcoholic Liver Disease
(AUD+ALD Trial)
Recruiting in Palo Alto (17 mi)
Overseen ByVatsalya Vatsalya, MD PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Louisville
Must not be taking: Psychotropics, Naltrexone, Acamprosate, others
Disqualifiers: Schizophrenia, Bipolar, Cancer, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests if taking a probiotic called LGG for several months can help people with heavy drinking and liver damage. The study aims to see if LGG can reduce drinking, improve liver health, and lower inflammation by improving gut health. LGG has been shown to improve intestinal barrier function and alleviate liver injury induced by alcohol consumption in animal models.
Will I have to stop taking my current medications?
The trial requires that you have not been on certain medications like naltrexone, acamprosate, topiramate, or disulfiram for at least one month before starting. Also, if you are currently using psychotropic medications that cannot be stopped, you may not be eligible to participate.
What data supports the effectiveness of the treatment Lactobacillus rhamnosus GG for alcoholic liver disease?
Research shows that Lactobacillus rhamnosus GG (LGG) can help reduce liver injury and improve liver health in people with alcohol-related liver problems by enhancing the gut barrier and reducing harmful substances in the blood.
12345Is Lactobacillus rhamnosus GG (LGG) safe for human use?
Lactobacillus rhamnosus GG (LGG) is generally considered safe for human use and has been shown to have protective effects on the gut and liver in various studies. It is used as a probiotic, which means it can help maintain a healthy balance of bacteria in the gut, and has been studied for its benefits in liver health, particularly in conditions related to alcohol use.
13567How does the treatment Lactobacillus rhamnosus GG differ from other treatments for alcoholic liver disease?
Lactobacillus rhamnosus GG (LGG) is unique because it is a probiotic that helps improve gut health and reduce liver damage by restoring the balance of intestinal bacteria and reducing inflammation. Unlike traditional medications, LGG works by enhancing the intestinal barrier and regulating immune responses, which can help prevent liver injury caused by alcohol.
13578Eligibility Criteria
This trial is for adults aged 21-65 with Alcohol Use Disorder and moderate Alcoholic Hepatitis. Participants must be heavy drinkers, have specific liver enzyme levels, not use drugs other than marijuana, and cannot be at high risk of suicide or on certain psychotropic meds. Pregnant women or those with severe medical conditions like cancer or cirrhosis are excluded.Inclusion Criteria
50 <AST<400 U/L; AST > ALT; and ALT < 200 U/L; total bilirubin > 1.2 mg/dL
Good health as confirmed by medical history, physical examination, ECG, laboratory tests and vital signs except for liver injury and AUD related history
I am not pregnant and am using birth control.
+9 more
Exclusion Criteria
Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) >10, at screening for more than 3 days
In the investigators' opinion, moderate to severe risk of suicide (e.g., active plan, or recent attempt in last 6 months)
I needed more than 2 blood transfusions due to stomach bleeding in the last 2 weeks.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either Lactobacillus Rhamnosus GG or placebo daily for 6 months to treat Alcohol Use Disorder and liver injury in Alcoholic Hepatitis
24 weeks
Monthly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests if a 6-month course of Lactobacillus Rhamnosus GG (LGG), a probiotic, is more effective than a placebo in treating liver injury in patients with Alcohol Use Disorder and Alcoholic Hepatitis. It also examines the effects on gut-brain axis markers and inflammation.
2Treatment groups
Active Control
Placebo Group
Group I: Active Comparator: Lactobacillus Rhamnosus GGActive Control1 Intervention
Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.
Group II: Placebo Comparator: Placebo for ProbioticPlacebo Group1 Intervention
Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.
Lactobacillus Rhamnosus GG is already approved in European Union, United States for the following indications:
๐ช๐บ Approved in European Union as Lacticaseibacillus rhamnosus GG for:
- Diarrhea in children
- Antibiotic-associated diarrhea
- Atopic dermatitis
- Allergic reactions
๐บ๐ธ Approved in United States as Lacticaseibacillus rhamnosus GG for:
- Diarrhea in children
- Antibiotic-associated diarrhea
- Traveler's diarrhea
- Irritable bowel syndrome
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Louisville HospitalLouisville, KY
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Who Is Running the Clinical Trial?
University of LouisvilleLead Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)Collaborator
References
Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease. [2022]We have previously demonstrated that Lactobacillus rhamnosus GG culture supernatant (LGGs) prevents acute-alcohol-exposure-induced hepatic steatosis and injury. The protective effects of LGGs were attributed to the improved intestinal barrier function leading to decreased endotoxemia. The purpose of this study was to determine whether LGGs was effective in protecting against chronic-alcohol-induced hepatic steatosis and injury and to evaluate the underlying mechanisms of LGGs on hepatic lipid metabolism.
The Beneficial Effects of Lactobacillus GG Therapy on Liver and Drinking Assessments in Patients with Moderate Alcohol-Associated Hepatitis. [2023]We investigated the effect of daily oral Lactobacillus rhamnosus GG (LGG) in reducing liver injury/severity and drinking in patients with alcohol use disorder and moderately severe alcohol-associated hepatitis.
Lactobacillus rhamnosus CCFM1107 treatment ameliorates alcohol-induced liver injury in a mouse model of chronic alcohol feeding. [2022]Lactobacillus rhamnosus CCFM1107 was screened for high antioxidative activity from 55 lactobacilli. The present study attempted to explore the protective properties of L. rhamnosus CCFM1107 in alcoholic liver injury. A mouse model was induced by orally feeding alcohol when simultaneously treated with L. rhamnosus CCFM1107, the drug Hu-Gan- Pian (HGP), L. rhamnosus GG (LGG), and L. plantarum CCFM1112 for 3 months. Biochemical analysis was performed for both serum and liver homogenate. Detailed intestinal flora and histological analyses were also carried out. Our results indicated that the administration of L. rhamnosus CCFM1107 significantly inhibited the increase in the levels of serum aminotransferase and endotoxin, as well as the levels of triglyceride (TG) and cholesterol (CHO) in the serum and in the liver. Glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were elevated while the levels of malondialdehyde (MDA) were decreased. The enteric dysbiosis caused by alcohol was restored by increasing the numbers of both lactobacilli and bifidobacteria and decreasing the numbers of both enterococci and enterobacter. Histological analysis confirmed the protective effect of L. rhamnosus CCFM1107. Compared with the other lactobacilli and to the drug Hu-Gan-Pian, there is a high chance that L. rhamnosus CCFM1107 provides protective effects on alcoholic liver injury by reducing oxidative stress and restoring the intestinal flora.
The effect of Lactobacillus rhamnosus B10 on alcoholic liver injury and intestinal microbiota in alcohol-induced mice model. [2022]Lactobacillus rhamnosus B10 (L. rhamnosus B10) isolated from the baby feces was given to an alcohol mice model, aiming to investigate the effects of L. rhamnosus B10 on alcoholic liver injury by regulating intestinal microbiota. C57BL/6N mice were fed with liquid diet Lieber-DeCarli with or without 5% (v/v) ethanol for 8 weeks, and treated with L. rhamnosus B10 at the last 2 weeks. The results showed that L. rhamnosus B10 decreased the serum total cholesterol (1.48 mmol/L), triglycerides (0.97 mmol/L), alanine aminotransferase (26.4 U/L), aspartate aminotransferase (14.2 U/L), lipopolysaccharide (0.23 EU/mL), and tumor necrosis factor-ฮฑ (138 pg/mL). In addition, L. rhamnosus B10 also reduced the liver triglycerides (1.02 mmol/g prot), alanine aminotransferase (17.8 mmol/g prot) and aspartate aminotransferase (12.5 mmol/g prot) in alcohol mice, thereby ameliorating alcohol-induced liver injury. The changes of intestinal microbiota composition on class, family and genus level in cecum were analyzed. The intestinal symbiotic abundance of Firmicutes was elevated while gram-negative bacteria Proteobacteria and Deferribacteres was decreased in alcohol mice treated with L. rhamnosus B10 for 2 weeks. In summary, this study provided evidence for the therapeutic effects of probiotics on alcoholic liver injury by regulating intestinal flora.
Lactobacillus rhamnosus GG combined with inosine ameliorates alcohol-induced liver injury through regulation of intestinal barrier and Treg/Th1 cells. [2022]Intestinal epithelial barrier disruption and bacterial translocation exacerbates the progression of alcoholic liver disease. Lactobacillus rhamnosus GG (LGG), a probiotic, has been shown benefits in chronic liver disease and in regulating gut dysbiosis. Previous studies showed the protective roles of LGG in ethanol-disrupted gut barrier functions and liver injury. Inosine, a metabolite produced by intestinal bacteria, has the anti-inflammatory and immunregulatory functions. In this study, the synergistic effect of LGG and inosine was investigated in a mouse model of alcohol-induced liver disease (ALD).
[Prophylactic effect of Lactobacillus GG in animal colitis and its effect on cytokine secretion and mucin gene expressions]. [2017]Lactobacillus rhamnosus GG (LGG) has been used in acute colitis treatment. However, it is unclear whether the LGG prevents chronic colitis. The aim of this study was to examine the prophylactic effect of LGG on animal colitis, cytokine secretion, and mucin gene expression.
[Cholic acid metabolism in human fecal cultures during diet supplementation with Lacto-bacillus rhamnosus GG]. [2006]Lactobacillus rhamnosus GG is used as probiotic and is thought to have protective properties in the human gastrointestinal tract and in other organs. Enrichment of the bile acid pool with secondary bile acids is common in some hepatic and gastrointestinal diseases and this is considered as a pathogenic element in the disease progression. The aim of this study was to evaluate the effect of probiotic feeding on fecal bile acid biotransformation, particularly on the production of secondary bile acids.
Lactobacillus rhamnosus Granules Dose-Dependently Balance Intestinal Microbiome Disorders and Ameliorate Chronic Alcohol-Induced Liver Injury. [2022]As the functions of Lactobacilli become better understood, there are increasing numbers of applications for Lactobacillus products. Previously, we have demonstrated that Lactobacillus rhamnosus GG (LGG) can prevent alcoholic liver injury. LGG granules were produced by fluid bed granulation with a media composed of starch, skimmed milk powder, whey powder, microcrystalline cellulose and maltose, and LGG fermented liquid that comprised 30-50% of the total weight. We found LGG granules dose-dependently protected against chronic alcoholic liver disease. When alcohol was consumed for 8 weeks with LGG treatment during the last 2 weeks, we demonstrated that the dose dependence of LGG granules can improve alcohol-induced liver injury through decreasing the levels of lipopolysaccharide and tumor necrosis factor-α in serum and prevent liver steatosis by suppressing triglyceride, free fatty acid, and malondialdehyde production in liver. Alcohol feeding caused a decline in the number of both Lactobacillus and Bifidobacterium, with a proportional increase in the number of Clostridium perfringens in ileum, and expansion of the Gram-negative bacteria Proteobacteria, Campylobacterales, and Helicobacter in cecum. However, LGG granule treatment restored the content of these microorganisms. In conclusion, LGG granule supplementation can improve the intestinal microbiota, reduce the number of gram-negative bacteria, and ameliorate alcoholic liver injury.