Ezetimibe Versus Placebo in the Treatment of Non-alcoholic Steatohepatitis

NCT01766713 | Completed Phase 2 Results

• 1 other identifier: EZE
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Non Alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Change in Liver Fat as Measured by MRI-PDFF

  Baseline, 24 weeks

Study Arms (2)

Ezetimibe

EXPERIMENTAL

10 mg/day of Ezetimibe

Drug: Ezetimibe

Placebo

PLACEBO COMPARATOR

one tablet per day (identical to ezetimibe)

Drug: Ezetimibe

Interventions

Ezetimibe DRUG

10mg daily oral dose of ezetimibe

Also known as: Zetia, Ezetrol

Ezetimibe; Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Evidence of (definite) steatohepatitis on liver biopsy done within the previous 12 months with a NASH activity score of at least 4 (of a total possible score of 8) including a score of at least 1 each for steatosis, hepatocellular injury and parenchymal inflammation. Histological criteria of steatohepatitis include: (1) macrovesicular steatosis, (2) acinar zone 3 hepatocellular injury (ballooning degeneration), (3) parenchymal and (4) portal inflammation. Additionally helpful, but not required, features include the presence of (5) Mallory's hyaline and (6) pericellular and/or sinusoidal fibrosis that predominantly involves zone 3. If a liver biopsy is available within the last 12 months, then a repeat biopsy may not be conducted unless there has been a considerable change in body weight that may change liver histologic parameters associated with NASH
• Those who are suspected of having NASH and have not undergone a liver biopsy within the last 12 months may undergo a liver biopsy as a screening liver biopsy but would qualify for randomization into either ezetimibe or placebo arms only if they meet histologic criteria of NASH.
• Written informed consent.

You may not qualify if:

• Evidence of another form of liver disease.
• Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg).
• Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum.
• Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
• Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis.
• Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
• Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
• Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.
• Drug-induced liver disease as defined on the basis of typical exposure and history.
• Bile duct obstruction as shown by imaging studies.
• History of excess alcohol ingestion, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day: 7 drinks per week) in the previous one year.
• Contraindications to liver biopsy: platelet counts \< 75,000/mm3 or prothrombin time \>16 seconds or history of bleeding disorders
• Decompensated liver disease, Child-Pugh score greater than or equal to 7 points
• History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months.
• Recent initiation or change of anti-diabetic drugs, including insulin, sulfonylureas, or thiazolidinediones in the previous 90 days.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California, San Diego

San Diego, California, 92103, United States

Location

Related Publications (2)

• Nedrud MA, Chaudhry M, Middleton MS, Moylan CA, Lerebours R, Luo S, Farjat A, Guy C, Loomba R, Abdelmalek MF, Sirlin CB, Bashir MR. MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials. Radiology. 2023 Mar;306(3):e220743. doi: 10.1148/radiol.220743. Epub 2022 Nov 1.

  PMID: 36318027 DERIVED

• Lin SC, Ang B, Hernandez C, Bettencourt R, Jain R, Salotti J, Richards L, Kono Y, Bhatt A, Aryafar H, Lin GY, Valasek MA, Sirlin CB, Brouha S, Loomba R. Cardiovascular risk assessment in the treatment of nonalcoholic steatohepatitis: a secondary analysis of the MOZART trial. Therap Adv Gastroenterol. 2016 Mar;9(2):152-61. doi: 10.1177/1756283X15621232.

  PMID: 26929777 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Rohit Loomba
• Organization: UCSD

roloomba@ucsd.edu

858-534-2624

Study Officials

• Rohit Loomba, MD, M.H.Sc

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine, Division of Gastroenterology, Department of Medicine and

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 11, 2013
• Study Start: January 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: September 1, 2014
• Last Updated: July 14, 2020
• Results First Posted: December 18, 2014

Record last verified: 2020-07

Locations

US (1)