Colesevelam Versus Placebo in the Treatment of Nonalcoholic Steatohepatitis

Phase 2

Completed

• Conditions: Nonalcoholic Steatohepatitis
• Interventions: Drug: Colesevelam Hcl

• Registration Number: NCT01066364
• Lead Sponsor: University of California, San Diego

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2010-02
• Study First Submitted: 2010-02-08
• Study First Submitted QC: 2010-02-09
• Study First Posted: 2010-02-10
• Primary Completion: 2012-02
• Study Completion: 2012-02
• Status Verified: 2020-07
• Results First Submitted: 2020-07-01
• Results First Submitted QC: 2020-07-01
• Last Update Submitted: 2020-07-01
• Results First Posted: 2020-07-21
• Last Update Posted: 2020-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

1. Age at entry at least 18 years.
2. 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.
3. Evidence of hepatic steatosis or liver fat (>5%) by MRI.
4. Evidence of definite or suspected NASH
5. Written informed consent.

Exclusion criteria:

1. Evidence of another form of liver disease.
2. History of excess alcohol ingestion.
3. Contraindications to liver biopsy.
4. Decompensated liver disease.
5. History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis.
6. Recent initiation or change of anti-diabetic drugs.
7. Use of colesevelam or other agents in the same class.
8. 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.
9. Positive test for anti-HIV.
10. Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year.
11. Pregnancy or inability to practice adequate contraception in women of childbearing potential.
12. Evidence of hepatocellular carcinoma

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colesevelam arm	Colesevelam Hcl	3.75 grams per day
Placebo (sugar) pill	Colesevelam Hcl	Six tablets per day (identical to colesevelam)

Primary Outcome Measures

Name	Time	Method
The Primary Outcome Will be Improvement in Hepatic Steatosis by Liver MRI	24 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Lipid Profiles	24 weeks	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.
Insulin Sensitivity as Determined by HOMA-IR	24 weeks	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.
Serum ALT and AST Values	24 weeks	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.

Trial Locations

Locations (2)

UCSD: Medical Center- Hillcrest; 🇺🇸 San Diego, California, United States

UCSD: Prevention Studies Clinic; 🇺🇸 La Jolla, California, United States