Colesevelam Versus Placebo in the Treatment of Nonalcoholic Steatohepatitis

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

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Colesevelam Hcl

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 Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • UCSD: Prevention Studies Clinic
    • San Diego, California, United States, 92103
      • UCSD: Medical Center- Hillcrest

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Daiichi Sankyo, Inc.
• Investigators: Principal Investigator: Rohit Loomba, MD, M.H.Sc, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2010
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: February 8, 2010
• First Submitted That Met QC Criteria: February 9, 2010
• First Posted (Estimate): February 10, 2010

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 1, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: NAFLD; NASH; Steatohepatitis; Fatty Liver Disease; Nonalcoholic
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride
• Other Study ID Numbers: 091491