The Efficacy of S-adenosyl Methionine (SAMe) Versus Pentoxiphylline in Patients With Non-alcoholic Steatohepatitis With Fibrosis

A Randomized Controlled Trial to Study the Efficacy of S-adenosyl Methionine (SAMe) Versus Pentoxiphylline in Patients With Non-alcoholic Steatohepatitis With Fibrosis.

Nonalcoholic fatty liver disease is one the most commonly encountered conditions in a daily outpatient Hepatology clinic. Secondly our country is the diabetic capital of the world and so the incidence of NAFLD (Non Alcoholic Fatty Liver Disease) is expected to rise in the future. It is a spectrum of hepatic pathology, ranging from simple steatosis, steatohepatitis, to cirrhosis. Nonalcoholic steatohepatitis (NASH) is a more advanced form of disease where steatosis is accompanied by hepatocyte injury as well as infiltration of inflammatory cells. Approximately 10-20% of patients with NASH may progress to cirrhosis. NASH is felt to be a major etiology of cryptogenic cirrhosis. Around 6230 human studies out of which 49 RCTs have been done till date to define the appropriate treatment of nonalcoholic steatohepatitis. However, still a controversy and no recommended treatment available till date. Recently published PIVENS trial has shown that Vitamin E has proven benefit in NASH. Other trials have also shown that pentoxiphylline has shown benefit in the form of histological improvement and biochemical improvement in the form of liver enzymes. Role of SAMe has been studied in alcoholic liver disease and showed to improve in both biochemical and histological features. However the usefulness of SAMe in NAFLD is not known till now. Hence this study has been designed.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: S-adenosylmethionine (SAMe); Drug: pentoxiphylline (PTX)

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110070
      • Institute of Liver & Biliary Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 70 years
• Persistently abnormal ALT >1.2 times upper limit of normal
• Histological evidence of NASH (Non alcoholic Steatohepatitis) on liver biopsy. The minimal criteria for diagnosis of NASH included the presence of lobular inflammation and fibrosis up to stage 3 as per Burnt stating.

Exclusion Criteria:

• Alcohol intake of more than 40gm / week with features suggestive chronic liver disease .
• Other known cause of chronic liver disease like Hepatitis B,C, autoimmune liver disease, Wilson's disease, alpha 1 antitrypsin deficiency and hemochromatosis, primary biliary cirrhosis, PSC (Primary Sclerosis Cholangitis).
• Patient on Medication like estrogens, amiodarone, MTx, tamoxifen, ATT (Antitubercular Treatment)
• Pregnancy or lactation
• Hypersensitivity to methylxanthines (e.g., caffeine, theophylline,)
• Recent retinal/cerebral hemorrhage
• Acute myocardial infarction or severe cardiac arrhythmias.
• Impaired renal function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-adenosylmethionine (SAMe)	Drug: S-adenosylmethionine (SAMe)
Active Comparator: pentoxiphylline (PTX)	Drug: pentoxiphylline (PTX)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Biochemical improvement in the form of AST/ALT	1 Years
Improvement in LSM (Liver Stiffness Measurement) & CAP (Controlled Attenuation Parameter)	1 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic response in form of anthropometry.	metabolic response in form of anthropometry (BMI, waist circumference).	1 Years
Fasting lipid profiles		1 Years
Reduction in uric acid levels		1 Years
Reduction in pro- inflammatory cytokines		1 Years
Histological outcome in the form of improvement or non- progression in hepatocyte injury and fibrosis.		1 years

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India
• Investigators: Principal Investigator: Dr Devaraja R, MD, Institute of liver and Biliary Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): July 31, 2015
• Study Completion (Actual): July 31, 2015

Study Registration Dates

• First Submitted: August 30, 2014
• First Submitted That Met QC Criteria: September 3, 2014
• First Posted (Estimate): September 4, 2014

Study Record Updates

• Last Update Posted (Actual): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 25, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: ILBS-NASH-01