SAMe for Liver Cirrhosis

Recruiting at 1 trial location

Overseen By Emory Latz

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Indiana University

Must not be taking: Antipsychotics

Disqualifiers: Hepatitis, HIV, Renal failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

196 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a supplement called SAMe (S-adenosylmethionine) can improve liver function in individuals with alcoholic cirrhosis, a condition where alcohol use damages the liver. The goal is to determine if SAMe can enhance liver health and reduce the risk of death compared to a placebo (a pill with no active ingredient). Individuals with alcoholic cirrhosis diagnosed with Child Class A or B liver status might be suitable candidates. Participants will be randomly assigned to receive either the SAMe supplement or a placebo to compare outcomes. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that SAMe is likely to be safe for humans?

Research has shown that SAMe (S-adenosylmethionine) is generally safe for individuals with liver problems. Studies have found that SAMe can improve liver health, with only minor side effects, mostly mild stomach issues that resolve quickly. One study also found improved liver function in people taking SAMe, suggesting it might help protect the liver from damage. Overall, SAMe appears well-tolerated by patients, making it a promising option for supporting liver health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

SAMe, or S-adenosylmethionine, is unique because it offers a new approach to treating liver cirrhosis, particularly cirrhosis caused by alcohol. Unlike traditional treatments that focus on managing symptoms or complications, SAMe works by potentially enhancing liver function and promoting liver cell regeneration. Researchers are excited about SAMe because it is a natural compound that the body already produces, suggesting it might have fewer side effects compared to synthetic drugs. Additionally, its antioxidant properties and ability to support detoxification processes make it a promising candidate for protecting and repairing liver tissue.

What evidence suggests that SAMe might be an effective treatment for liver cirrhosis?

Research shows that SAMe (S-adenosylmethionine) might improve liver function in people with alcohol-related liver damage. Some studies found that long-term use of SAMe can lead to better survival rates and delay the need for a liver transplant. Many studies consistently show improvements in liver function. However, not all research agrees, and some studies found SAMe no more effective than a placebo (a pill with no active ingredients). In this trial, participants will receive either SAMe or a placebo to evaluate its effectiveness. Overall, evidence suggests SAMe could be helpful, but results vary. ^{1 3 4 6 7}

Who Is on the Research Team?

Suthat Liangpunsakul, MD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• SAMe

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.

How Is the Trial Designed?

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+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

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-adenosyl-L-methionine (SAMe) plays a crucial role in various cellular processes, including the synthesis of glutathione and methylation reactions, which are important for liver health.

Although pre-clinical studies suggest that SAMe may help protect the liver and improve disease severity, there is currently a lack of large, high-quality randomized clinical trials to confirm its effectiveness in treating liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a trial involving 220 patients with chronic liver disease, oral S-adenosylmethionine (1600 mg/day) significantly reduced serum markers of cholestasis and improved symptoms like itching and fatigue compared to placebo.

The treatment was well-tolerated, with no significant safety concerns, making oral S-adenosylmethionine a promising option for managing intrahepatic cholestasis in patients with liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Frezza, M., Surrenti, C., Manzillo, G., et al.[2019]

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]

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]

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]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0168827899802633

S-Adenosylmethionine in alcoholic liver cirrhosis

The present results indicate that longterm treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic liver cirrhosis.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/10406187/

S-adenosylmethionine in alcoholic liver cirrhosis

Conclusions: The present results indicate that long-term treatment with AdoMet may improve survival or delay liver transplantation in patients with alcoholic ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11547595/

S-Adenosylmethionine (SAMe) for Liver Health

Improvements in liver function were seen in all 15 studies. SAMe significantly improved liver function in all studies evaluating chemotherapy- ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04250259?term=peptide

SAMe Trial for Patients With Alcoholic Cirrhosis

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 ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0168827812004096

S-adenosylmethionine (SAMe) therapy in liver disease

The results led the authors to conclude that 'SAMe was no more effective than placebo' in the treatment of ALD [75], [87]. It is interesting to note that ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3315189/

S-ADENOSYLMETHIONINE TREATMENT OF ALCOHOLIC ...

A fibrosis score of 3 or more, indicative of bridging or cirrhosis, was present in 7/12 (58.3%) in both the SAM and the placebo group.

7.

journal-of-hepatology.eu

journal-of-hepatology.eu/article/s0168-8278(12)00409-6/fulltext

S-adenosylmethionine (SAMe) therapy in liver disease

Despite encouraging pre-clinical data confirming that SAMe depletion can exacerbate liver injury and supporting a hepatoprotective role for SAMe therapy.