Colesevelam Versus Placebo in the Treatment of Nonalcoholic Steatohepatitis

Study Overview
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Brief Summary
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The purpose of the study is to see if the drug colesevelam is a potential treatment for Nonalcoholic Steatohepatitis(NASH).

Detailed Description
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We plan to investigate the role of colesevelam, a bile-acid binding resin, in patients with NASH residing in the United States and assess liver fat changes during therapy using MRI of the liver. It can be hypothesized that colesevelam would lead to a greater improvement in insulin sensitivity and lipid profile compared with placebo and may lead to greater improvement in liver fat by MRI as compared to placebo. In this pilot study, we propose to randomize approximately 55 patients (1:1 ratio) to either colesevelam or placebo and treat them for 24-weeks to evaluate changes in baseline insulin sensitivity, serum biochemistry (ALT and AST), and liver fat by MRI during therapy. Liver histologic changes would also be examined as an exploratory outcome for future studies.

Official Title
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Colesevelam Versus Placebo in the Treatment of Nonalcoholic Steatohepatitis

Conditions
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Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Colesevelam Hcl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at entry at least 18 years. Serum alanine (ALT) or aspartate (AST) aminotransferase activities that are above the upper limits of normal. 19 or more in women and 30 or more in men. Evidence of hepatic steatosis or liver fat (>5%) by MRI. Evidence of definite or suspected NASH Written informed consent. Exclusion criteria: Evidence of another form of liver disease. History of excess alcohol ingestion. Contraindications to liver biopsy. Decompensated liver disease. History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis. Recent initiation or change of anti-diabetic drugs. Use of colesevelam or other agents in the same class. Significant systemic or major illnesses other than liver disease that, in the opinion of the investigator would preclude treatment with colesevelam and adequate follow up. Positive test for anti-HIV. Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year. Pregnancy or inability to practice adequate contraception in women of childbearing potential. Evidence of hepatocellular carcinoma

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (sugar) pill<br>Six tablets per day (identical to colesevelam) | Drug: Colesevelam Hcl<br>* 3.75 gm/day (six 675 mg tablets)<br>* Other names: Welchol;|
| Experimental: Colesevelam arm<br>3.75 grams per day | Drug: Colesevelam Hcl<br>* 3.75 gm/day (six 675 mg tablets)<br>* Other names: Welchol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome Will be Improvement in Hepatic Steatosis by Liver MRI | To examine the efficacy of Colesevelam at 3.75 g/day orally versus placebo to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity as Determined by HOMA-IR | To examine the efficacy of Colesevelam at 3.75 g/day orally versus placebo to decrease HOMA-IR in patients with biopsy-proven nonalcoholic steatohepatitis. | 24 weeks | 
| Serum ALT and AST Values | To examine the efficacy of Colesevelam at 3.75 g/day orally versus placebo to decrease serum ALT and AST in patients with biopsy-proven nonalcoholic steatohepatitis. | 24 weeks | 
| Lipid Profiles | To examine the efficacy of Colesevelam at 3.75 g/day orally versus placebo to decrease improve the lipid profiles in patients with biopsy-proven nonalcoholic steatohepatitis. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NASH, NAFLD, Steatohepatitis, Nonalcoholic, Fatty Liver Disease