SAMe Trial for Patients With Alcoholic Cirrhosis

Phase 2RecruitingNCT04250259

Indiana University196 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

196

Conditions

Alcoholic Cirrhosis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria for patients with alcoholic cirrhosis 1. Evidence of cirrhosis as per clinical signs and/or noninvasive transient elastography (Fibroscan®), computed tomography, magnetic resonance imaging including MRI elastography compatible with cirrhosis and/or histopathology by biopsy and 2. subjects with clinical presentation either in Child Class A or B at the time of enrollment 3. individuals 18 to 70 years old and may or may not consume alcohol during study. Inclusion criteria for healthy control : ) individuals 18 to 70 years old (2) able to provide informed consent (3) 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 (4) subjects are healthy without underlying acute or chronic medical conditions. Exclusion criteria for patients with alcoholic cirrhosis 1. Active infection as evidenced by positive urine culture, blood culture, or pneumonia, 2. Known co-existing infection with hepatitis C, hepatitis B, or HIV 3. Significant systemic or major illness including chronic obstructive pulmonary disease, congestive heart failure, and renal failure that in the opinion of the Investigator would preclude the patient from participating in and completing the study 4. Gastrointestinal bleeding within the prior 28 days3 5. Participation in another investigational drug, biologic, or medical device trial within 30 days prior to screening 6. Women who are pregnant, may become pregnant, or nursing 7. Presence of any other disease or condition that is interfering with the absorption, distribution, metabolism, or excretion of SAMe such as those with gastric bypass surgery 8. Subjects with history of/diagnosis of hepatocellular carcinoma 9. 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 10. Subjects with psychiatric illnesses such as bipolar disorders as SAMe may interfere with the levels of anti-psychotic drugs and 11. Subjects who are immunocompromised Exclusion criteria for all healthy control participants: 1. subjects with an active and serious medical disease 2. subjects with an infectious disease 3. consume any alcohol within 3 months before the study 4. subjects with localized or systemic infection

Outcomes

Primary Outcomes

SAMe supplement's effect on all-cause mortality

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.

Time frame: Baseline to end of 24 months

Secondary Outcomes

SAMe supplement's effect on intestinal permeability function, as defined by serum lipopolysaccharides (LPS)

The function of intestinal permeability will be evaluated by testing serum lipopolysaccharides (LPS) in patients who receive SAMe compared to those who receive placebo. Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins.

Time frame: baseline to end of 24 months

SAMe supplement's effect on cellular oxidative stress and/or endoplasmic reticulum (ER) stress, as defined by mitochondrial DNA

Cellular oxidative stress and/or endoplasmic reticulum (ER) stress will be evaluated by measuring the levels of mitochondrial DNA in the blood of patients who receive SAMe compared to those who receive placebo.