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Non Alcoholic SteatohepatitisPhase 2NCT01766713

Ezetimibe Versus Placebo in the Treatment of Non-alcoholic Steatohepatitis

A Phase 2 study testing Ezetimibe in people with Non Alcoholic Steatohepatitis, run by University of California, San Diego at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 100 yearsHealthy volunteers can take part
Conditions the study is for
Non Alcoholic Steatohepatitis
What is being tested?
Ezetimibe
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
50 participants
Where
1 siteUnited States
Study dates
Jan 2013to Sep 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Use of ezetimibe or other agents in the same class within the 90 days prior to randomization and/or liver biopsy.
  • Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator would preclude treatment with ezetimibe 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: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study that is suggestive of liver cancer.
  • Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibility hinder completion of the study.
  • Serum creatinine >1.5 mg/dl.
  • Contraindications to ezetimibe use :
  • History of allergic reaction to ezetimibe
  • patients with acute liver injury or unexplained persistent elevations in ALT > 500 U/L
  • Women who are pregnant or may become pregnant
  • Nursing mothers
  • Contraindications to MRI:
  • The subject has any contraindication to MR imaging, such as patients with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field.
  • The subject has a history of extreme claustrophobia
  • The subject cannot fit inside the MR scanner cavity

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Diego

    San Diego, California, 92103

Other trials in United States

About this study

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

Read the detailed description

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. Nonalcoholic steatohepatitis (NASH) represents the more severe end of this spectrum and is characterized by steatosis, ballooning degeneration and lobular inflammation with or without fibrosis. The etiology of NASH is not completely understood, but it is often associated with obesity, type 2 diabetes, hyperlipidemia and insulin resistance. Lipotoxicity, insulin resistance and oxidative stress appear to be central to the pathogenesis of NASH. Currently, there is no FDA approved treatment for NAFLD/NASH. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. Ezetimibe is an LDL lowering agent that works through inhibition of the fat absorption from the small intestine. In this study, we propose to treat 50 patients with NASH with either Ezetimibe or placebo for 24 weeks. After an initial evaluation for insulin sensitivity, MRI liver fat distribution and liver biopsy, patients will receive either 10 mg/day of Ezetimibe or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of Ezetimibe and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and liver biopsy. Pre and post treatment MRI-derived liver fat content, liver histology and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity, liver histology and liver biochemistry.

Being tested
Ezetimibe
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EzetimibeDrug

    Also called Zetia, Ezetrol

    10mg daily oral dose of ezetimibe

Study groups in NCT01766713
Study groupRoleWhat they receive
EzetimibeExperimental10 mg/day of Ezetimibe
Receives: Drug: Ezetimibe
PlaceboPlacebo comparatorone tablet per day (identical to ezetimibe)
Receives: Drug: Ezetimibe

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Liver Fat as Measured by MRI-PDFF

    Measured: Baseline, 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jan 2013 (estimated)
  2. Study startJan 2013
  3. Primary completionAug 2014
  4. Study completionSep 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01766713
Sponsor's protocol ID
EZE
Status last verified
Jul 2020
First submitted
9 Jan 2013
Last updated
14 Jul 2020
Data monitoring committee
No

Publications

  • 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.

    PubMed 36318027

  • 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. Ther Adv Gastroenterol. 2016 Mar;9(2):152-61. doi: 10.1177/1756283X15621232.

    PubMed 26929777

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ezetimibe in people with Non Alcoholic Steatohepatitis, run by University of California, San Diego at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Liver Fat as Measured by MRI-PDFF (time frame: Baseline, 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01766713, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2020.

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