Probiotic LGG for Alcoholic Liver Disease

(AUD+ALD Trial)

Overseen By Amber Jackson, BS CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Louisville

Must not be taking: Psychotropics, Naltrexone, Acamprosate, others

Disqualifiers: Schizophrenia, Bipolar, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the probiotic supplement Lactobacillus Rhamnosus GG (LGG) can improve liver health and alcohol use behavior in individuals with Alcohol Use Disorder (AUD) and moderate liver damage. The study compares LGG's effects to a placebo (a pill with no active ingredients) over six months to determine if it reduces inflammation and enhances gut-brain interactions. Suitable candidates for this trial include those who have been heavy drinkers for at least three months, have a diagnosis of AUD, and exhibit some liver damage. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that Lactobacillus Rhamnosus GG is likely to be safe for humans?

Research has shown that Lactobacillus rhamnosus GG (LGG) is safe for use. In a 6-month study, LGG not only proved safe but also helped reduce liver damage and heavy drinking in people with Alcohol Use Disorder (AUD). Another study found that LGG improved liver function and reduced the buildup of liver fat caused by alcohol. Additionally, LGG lowered liver inflammation and decreased certain harmful substances in the liver.

These findings suggest that LGG is well-tolerated and may positively affect liver health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alcoholic Liver Disease?

Most treatments for alcoholic liver disease focus on lifestyle changes and medications to manage symptoms. But Lactobacillus Rhamnosus GG (LGG) offers a unique approach. Unlike standard treatments, LGG is a probiotic that works by potentially restoring gut health and reducing inflammation, which are key issues in liver disease. Researchers are excited about LGG because it targets the gut-liver axis, offering a fresh angle on tackling the root causes of liver damage rather than just managing symptoms. This could lead to a more holistic and effective treatment option for those struggling with alcoholic liver disease.

What evidence suggests that Lactobacillus Rhamnosus GG might be an effective treatment for Alcoholic Liver Disease?

This trial will compare the effects of Lactobacillus rhamnosus GG (LGG) with a placebo in participants with liver problems related to Alcohol Use Disorder (AUD). Research has shown that LGG might help with liver issues. Specifically, earlier studies found it reduced liver damage and heavy drinking after six months of use. It also improved liver health by lowering harmful substances in the blood caused by alcohol. Additionally, LGG protected the liver by strengthening the gut barrier, preventing harmful substances from reaching the liver. These findings suggest that LGG could effectively treat liver issues linked to alcohol use. ^{1 2 5 6 7}

Who Is on the Research Team?

Vatsalya Vatsalya, MD

Principal Investigator

Department of Medicine, University of Louisville

Harsh Tiwari, MD

Principal Investigator

University of Louisville

Craig J McClain, MD

Principal Investigator

Department of Medicine, University of Louisville

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Lactobacillus Rhamnosus GG
• Placebo for Probiotic

Trial Overview 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.

How Is the Trial Designed?

Group I: Active Comparator: Lactobacillus Rhamnosus GG Active Control 1 Intervention

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

Group II: Placebo Comparator: Placebo for Probiotic Placebo Group 1 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:

Approved in European Union as Lacticaseibacillus rhamnosus GG for:

• Diarrhea in children
• Antibiotic-associated diarrhea
• Atopic dermatitis
• Allergic reactions

Approved in United States as Lacticaseibacillus rhamnosus GG for:

• Diarrhea in children
• Antibiotic-associated diarrhea
• Traveler's diarrhea
• Irritable bowel syndrome

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

In a study of 46 individuals with alcohol use disorder and moderate alcohol-associated hepatitis, daily oral Lactobacillus rhamnosus GG (LGG) significantly reduced liver injury after just one month of treatment.

After six months of LGG treatment, participants showed a marked decrease in heavy drinking, reaching levels of social drinking or abstinence, indicating potential benefits for both liver health and alcohol consumption behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Beneficial Effects of Lactobacillus GG Therapy on Liver and Drinking Assessments in Patients with Moderate Alcohol-Associated Hepatitis. Vatsalya, V., Feng, W., Kong, M., et al.[2023]

In a study involving six healthy volunteers, the probiotic Lactobacillus rhamnosus GG did not show a statistically significant effect on the conversion of cholic acid to deoxycholic acid, although three participants exhibited a strong response, suggesting variability in individual responses to probiotics.

The findings indicate that individuals with higher baseline production of secondary bile acids may benefit more from probiotic treatment, highlighting the potential for targeted probiotic therapies in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cholic acid metabolism in human fecal cultures during diet supplementation with Lacto-bacillus rhamnosus GG]. Mirasoli, M., Roda, A., Montagnani, M., et al.[2006]

Lactobacillus rhamnosus CCFM1107 showed significant protective effects against alcoholic liver injury in a mouse model, reducing harmful serum levels of aminotransferase, triglycerides, and cholesterol while increasing antioxidant levels like glutathione.

The study demonstrated that L. rhamnosus CCFM1107 not only mitigated oxidative stress but also restored healthy gut bacteria balance disrupted by alcohol, suggesting its potential as a therapeutic intervention for liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus CCFM1107 treatment ameliorates alcohol-induced liver injury in a mouse model of chronic alcohol feeding. Tian, F., Chi, F., Wang, G., et al.[2022]

Lactobacillus rhamnosus GG (LGGs) effectively prevents chronic alcohol-induced liver damage and fat accumulation in mice, as shown in a study where mice were fed a liquid diet with 5% alcohol for 4 weeks.

The protective effects of LGGs are linked to its ability to modulate key metabolic pathways, including enhancing fatty acid oxidation and reducing liver cell apoptosis, by regulating AMPK activation and the balance of pro-apoptotic and anti-apoptotic proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease. Zhang, M., Wang, C., Wang, C., et al.[2022]

In a study involving 64 BALB/c mice, Lactobacillus rhamnosus GG (LGG) demonstrated a protective effect against chronic colitis, as indicated by improved colon length and reduced disease activity index during repeated colitis exposure.

The beneficial effects of LGG appear to be linked to its ability to modulate cytokine levels and inhibit pathogenic bacteria, although it did not significantly affect mucin gene expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prophylactic effect of Lactobacillus GG in animal colitis and its effect on cytokine secretion and mucin gene expressions]. Moon, G., Myung, SJ., Jeong, JY., et al.[2017]

Lactobacillus rhamnosus GG (LGG) granules can significantly protect against chronic alcoholic liver disease, as shown in a study where alcohol was consumed for 8 weeks and LGG was administered during the last 2 weeks.

LGG treatment not only reduced liver injury markers and improved liver health by restoring beneficial gut bacteria but also decreased harmful gram-negative bacteria, highlighting its potential as a therapeutic intervention for alcohol-related liver damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus Granules Dose-Dependently Balance Intestinal Microbiome Disorders and Ameliorate Chronic Alcohol-Induced Liver Injury. Gu, Z., Wu, Y., Wang, Y., et al.[2022]

In a mouse model of alcohol-induced liver disease, the combination of Lactobacillus rhamnosus GG (LGG) and inosine significantly improved liver health by reducing liver enzymes, inflammation, and restoring gut barrier function compared to LGG alone.

The combined treatment also positively affected the gut microbiome and immune response, increasing regulatory T cells and decreasing Th1 cells, which suggests a comprehensive approach to managing alcohol-induced liver damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus GG combined with inosine ameliorates alcohol-induced liver injury through regulation of intestinal barrier and Treg/Th1 cells. Zhu, Y., Wang, X., Zhu, L., et al.[2022]

In a study involving C57BL/6N mice with alcohol-induced liver injury, treatment with Lactobacillus rhamnosus B10 for 2 weeks significantly reduced liver damage markers, including triglycerides and liver enzymes, indicating its potential efficacy in ameliorating alcohol-related liver injury.

The probiotic L. rhamnosus B10 also positively altered the intestinal microbiota by increasing beneficial Firmicutes and decreasing harmful Proteobacteria, suggesting a mechanism of action through the regulation of gut bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of Lactobacillus rhamnosus B10 on alcoholic liver injury and intestinal microbiota in alcohol-induced mice model. Li, X., Wang, Y., Zhang, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10524173/

The Beneficial Effects of Lactobacillus GG Therapy on Liver ... In summary, this 6-month pilot study showed that Lactobacillus rhamnosus GG was safe, attenuated liver injury, and reduced heavy alcohol intake in AUD patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0002944011008583

Lactobacillus rhamnosus GG Treatment Potentiates ... LGG supplementation significantly reduced alcohol-induced endotoxemia and hepatic steatosis and improved liver function. LGG restored alcohol-induced reduction ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7317518/

Probiotic Lactobacillus rhamnosus GG Prevents Liver Fibrosis ... LGG treatment significantly reduced serum levels of AST, ALP, and direct bilirubin and tended to reduce ALT and total bilirubin levels in BDL mice (Fig. 1A).

4. research.bidmc.org research.bidmc.org/gyongyi-szabo/publications/beneficial-effects-lactobacillus-gg-therapy-liver-and-drinking-assessments-patients

The Beneficial Effects of Lactobacillus GG Therapy on Liver ... RESULTS: LGG treatment was associated with a significant reduction in liver injury after 1 month. Six months of LGG treatment reduced heavy ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2665927124002910

Selenium enrichment enhances the alleviating effect of ... In particular, Lactobacillus and Bifidobacterium have been proven to effectively reduce alcohol-induced liver damage by enhancing intestinal barrier function, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3804118/

Lactobacillus rhamnosus GG reduces hepatic TNFα ... Two-weeks of LGG supplementation reduced hepatic inflammation and liver injury and markedly reduced TNFα expression. Alcohol feeding increased hepatic mRNA ...

7. journals.lww.com journals.lww.com/hep/fulltext/2020/06000/probiotic_lactobacillus_rhamnosus_gg_prevents.16.aspx

Probiotic Lactobacillus rhamnosus GG Prevents Liver... LGG treatment significantly attenuated liver inflammation, injury, and fibrosis with a significant reduction of hepatic BAs in BDL mice.