SAMe for Liver Cirrhosis

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Suthat Liangpunsakul, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Indiana University

Must not be taking: Antipsychotics

Disqualifiers: Hepatitis, HIV, Renal failure, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The proposed of this randomized, double blinded, placebo-controlled study is to assess the effect of SAMe compared to placebo in patients with alcoholic cirrhosis Child Class A and B. The primary objective of the study is to test relationship between SAMe (S-adenosylmethionine) supplement on liver function. The hypothesis is that SAMe supplement will improve liver function in patients with alcoholic liver disease. The improvement in liver function will lead to the reduction in all-cause mortality in patients with alcoholic cirrhosis in those who receive SAMe supplement when compared to those receiving placebo.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have psychiatric illnesses or are taking anti-psychotic drugs, SAMe may interfere with them.

What evidence supports the effectiveness of the drug SAMe for liver cirrhosis?

Research shows that SAMe can improve liver function in patients with liver cirrhosis by increasing important proteins in the blood and reducing symptoms like fatigue and itching. It has also been effective in other liver conditions, suggesting it may help protect the liver and improve symptoms. ^{1 2 3 4 5}

Is SAMe safe for use in humans, particularly for liver conditions?

Research suggests that SAMe (S-adenosylmethionine) is generally safe for use in humans, including those with liver conditions, as studies have shown improvements in liver function without significant adverse effects. However, large, high-quality clinical trials are still needed to fully establish its safety and effectiveness. ^{1 2 3 4 6}

How does the drug SAMe differ from other treatments for liver cirrhosis?

SAMe is unique because it addresses a deficiency in cirrhotic patients by improving liver cell function and albumin production, which other treatments like L-methionine and ATP do not achieve. It is also used in different forms, such as intravenous or oral, and has shown effectiveness in improving symptoms and liver function in various liver conditions. ^{1 2 4 5 6}

Research Team

Suthat Liangpunsakul, MD

Principal Investigator

Indiana University

Eligibility Criteria

This trial is for adults aged 18-70 with alcoholic cirrhosis in Child Class A or B, who have been heavy drinkers but are now sober for at least 3 months. They must be generally healthy without serious illnesses like heart failure or infections and not on certain medications that affect SAMe's action.

Inclusion Criteria

Subjects do not consume any alcohol or those who drink < 50 grams per day on average in women and < 80 grams per day on average in men and do not consume any alcohol within 3 months before the study and subjects are healthy without underlying acute or chronic medical conditions

I am healthy with no serious long-term or sudden illnesses.

Able to provide informed consent

Exclusion Criteria

I have hepatitis C, hepatitis B, or HIV.

Members from the same family of study participant. This is based on the recent paper on the non-random sampling in randomized controlled trials4. We acknowledge that if we assign family members to identical treatment, randomization would not be totally correct; but if properly randomized, there is a chance that the members of the family might mix the pills. To avoid this issue and maintain the integrity of randomized blinded fashion, we will not include members from the same family into the study

I do not have any major illnesses that would stop me from completing the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SAMe supplement or placebo for 24 months to assess its effect on liver function and other health outcomes

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Placebo (Placebo)
• SAMe (Supplement)

Trial Overview The study tests if a supplement called SAMe can improve liver function in patients with alcoholic cirrhosis compared to a placebo. Participants will randomly receive either the SAMe tablets or placebo, and researchers will monitor their liver health and overall survival.

Participant Groups

Group I: 1,200 mg SAMe Experimental Treatment 1 Intervention

SAMe supplement (SAMe 400 mg tablet), 2 tablets in the morning before breakfast and one tablet in the evening before dinner (a total dose of 1,200 mg daily) for 24 months

Group II: Non-drinking Controls Active Control 1 Intervention

Non-drinking healthy controls

Group III: Placebo Placebo Group 1 Intervention

Alcoholic Cirrhosis on placebo

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Alan Palkowitz

Indiana University

Chief Executive Officer since 2020

PhD in Chemistry from Indiana University

David Ingram

Indiana University

Chief Medical Officer since 2020

MD from Indiana University School of Medicine

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

David E. Cohen

Cedars-Sinai Medical Center

Chief Medical Officer

MD and PhD in Physiology and Biophysics from Harvard University

Peter L. Slavin

Cedars-Sinai Medical Center

Chief Executive Officer

MD from Harvard Medical School, MBA from Harvard Business School

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Dr. George F. Koob

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Chief Executive Officer since 2014

PhD in Neurobiology from the Scripps Research Institute

Dr. Patricia Powell

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Chief Medical Officer since 2015

MD from an accredited institution

Findings from Research

In a study of 15 patients with hepatic cirrhosis, intravenous or intramuscular treatment with 15 mg of S-adenosylmethionine (SAMe) four times a day for 30 days significantly improved liver cell function and albumin production.

In contrast, administering equivalent doses of L-methionine and ATP to another group of 15 cirrhotic patients did not produce the same beneficial effects, confirming that the improvements were specifically due to SAMe treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[S-Adenosylmethionine: plasma levels in hepatic cirrhosis and preliminary results of its clinical use in hepatology. Double-blind study]. Ideo, G.[2013]

In a randomized, double-blind trial involving 123 patients with alcoholic liver cirrhosis, treatment with S-adenosylmethionine (AdoMet) showed a trend towards reduced mortality and liver transplantation rates, decreasing from 30% in the placebo group to 16% in the AdoMet group, although this was not statistically significant overall.

When excluding patients with the most advanced liver disease (Child class C), AdoMet treatment significantly improved survival rates compared to placebo, with a mortality/liver transplantation rate of 12% versus 29%, highlighting its potential benefits in less advanced cases of cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. Mato, JM., Cámara, J., Fernández de Paz, J., et al.[2022]

S-adenosylmethionine treatment for 6 weeks significantly improved liver health in rats with carbon tetrachloride-induced cirrhosis by restoring glutathione levels and reducing lipid peroxidation, leading to less severe liver fibrosis.

Rats treated with S-adenosylmethionine for 6 weeks showed lower collagen and prolyl hydroxylase activity compared to those treated for only 3 weeks, indicating that longer treatment duration may enhance its protective effects against liver damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis. Gassó, M., Rubio, M., Varela, G., et al.[2019]

S-adenosylmethionine (AdoMet) shows significant early efficacy in reducing liver enzyme levels (ALT, AST, ALP, γGT) in patients with intrahepatic cholestasis, with notable improvements observed within 2 weeks of treatment in both randomized and non-randomized studies.

AdoMet also appears to alleviate symptoms of cholestasis, including fatigue and depression, with some patients reporting improvements as early as 2 weeks, indicating its potential as a beneficial treatment for chronic liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review. Noureddin, M., Sander-Struckmeier, S., Mato, JM.[2020]

References

1. Italy pubmed.ncbi.nlm.nih.gov

[S-Adenosylmethionine: plasma levels in hepatic cirrhosis and preliminary results of its clinical use in hepatology. Double-blind study]. [2013]

2. Netherlands pubmed.ncbi.nlm.nih.gov

S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

S-adenosylmethionine (SAMe) therapy in liver disease: a review of current evidence and clinical utility. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review. [2020]