Betaine in Patients With Nonalcoholic Steatohepatitis

A Randomized, Placebo-Controlled Trial of Betaine in Patients With Nonalcoholic Steatohepatitis (NASH)

To assess the safety and efficacy of betaine in patients with NASH on markers of disease severity such as liver histology, liver biochemistries, and health related quality of life.

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Cystadane; Drug: Identical Placebo

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida at Gainesville
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

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:

• Adult males or females, age 18 - 70 (inclusive) with NASH.
• Abnormal aminotransferase levels (1.5x normal) on at least two occasions at less three months apart.
• Histologic evidence of steatohepatitis on liver biopsy performed within six months of entry.
• Absence of sustained alcohol ingestion (less than 20 g/d in women or 30 g/d in men).
• Compensated liver disease and blood cell counts within the following limits: Hb > 12 gr/dl, platelets > 120,000/mm3, and WBC > 3,000/mm3
• TSH (thyroid-stimulating hormone) within normal limits of testing laboratory.
• Appropriate exclusion of other liver disease such as viral, autoimmune and metabolic/hereditary liver disease.
• If a history of diabetes, a hemoglobin A1C < 10.0%.
• Alpha-fetoprotein in normal range (obtained within the previous year), or if greater than normal, the patient requires a negative ultrasound for hepatocellular carcinoma within prior 3 months.
• Sexually active female patients of childbearing potential must practice adequate contraception during the treatment period and for 6 months after discontinuation of therapy. A pregnancy test obtained at entry prior to the initiation of treatment must by negative. Female patients must not be breast-feeding.
• Sexually active male patients must practice acceptable methods of contraception during the treatment period and for 6 months after discontinuation of therapy.
• Written informed consent for participation in this study.

Exclusion Criteria:

• Treatment with any experimental drug for NASH, betaine, ursodeoxycholic acid (URSO), methionine, rosiglitazone, metformin, pioglitazone, or vitamin E within 3 months of enrollment or at time of pre-entry liver biopsy. (Patients with diabetes and on stable medical management for six months prior to entry and an anticipated stable program throughout the study will be eligible. Medications that may be used include insulin, biguanides, thiazolidnediones, metformin, and sulfonylureas. Patients with hyperlipidemia on a medical program for control of lipids who have had a change in drug treatment in the preceding six months or with anticipated changes in the year of the study will also be eligible.)
• Any cause for the liver disease based on patient history and biopsy (where applicable) other than NASH
• Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices, spontaneous encephalopathy.
• Any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study such as significant cardiovascular dysfunction or chronic obstructive pulmonary disease requiring specific therapy
• Pregnancy or breastfeeding.
• Unwillingness of patient and/or partner to use contraception during treatment.
• Previous malignant disease (other than non-melanoma skin cancer) in the previous two years.
• Substance abuse, such as alcohol, I.V. drugs and inhaled drugs.
• Any other conditions that in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the protocol.
• Lactose intolerant patient since placebo preparation contains lactose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Identical Placebo	Drug: Identical Placebo; Placebo
Active Comparator: Cystadane	Drug: Cystadane; Betaine 20 mg a day or identical placebo for 1 year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
changes in degree of steatosis, necroinflammatory activity and fibrosis in liver biopsy.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary end-points will be changes in liver test results and health related quality of life.	1 year

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: University of Florida; Orphan Medical

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): January 7, 2008

Study Record Updates

• Last Update Posted (Estimate): April 8, 2015
• Last Update Submitted That Met QC Criteria: April 6, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Nonalcoholic Steatohepatitis; NASH; Betaine
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Lipotropic Agents; Betaine
• Other Study ID Numbers: 458-00