Using atorvastatin to treat nonalcoholic steatohepatitis (NASH)

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate the Safety and Efficacy of Statins in Adult Patients With Non-Alcoholic Steatohepatitis (NASH)

This study is testing whether atorvastatin, a cholesterol-lowering medication, can help people with nonalcoholic steatohepatitis (NASH) feel better and improve their liver health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Drugs / interventions: infliximab, adalimumab, methotrexate
• Locations: 2 sites (Rochester, Minnesota and 1 other locations)
• Trial ID: NCT04679376 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and effectiveness of atorvastatin, a medication commonly used to lower cholesterol, in improving the features of nonalcoholic steatohepatitis (NASH). Participants will be randomly assigned to receive either atorvastatin or a placebo, with their liver health monitored through biopsies and other assessments. The study focuses on individuals with confirmed NASH and specific fibrosis stages, ensuring a targeted approach to treatment. The trial is designed to gather data on how well atorvastatin can alleviate the symptoms and progression of this liver condition.

Who should consider this trial

Good fit: Ideal candidates for this study are adults with definite NASH confirmed by liver biopsy and a fibrosis stage of 2 or higher.

Not a fit: Patients with other chronic liver diseases, cirrhosis, or those currently on statin therapy will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from NASH, potentially improving liver health and reducing disease progression.

How similar studies have performed: While the use of statins for liver conditions is being explored, this specific approach for NASH is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* Definite NASH on a liver biopsy obtained ≤ 90 days prior to randomization with a NAFLD activity score (NAS) of ≥ 4 with at least 1 in each component of the NAS according to NASH CRN grading52
* Fibrosis stage ≥ 2 as assessed by liver biopsy
* Not currently on statin therapy
* Provision of written informed consent
* Agree to use of effective contraceptive measures if female of child bearing potential.

Exclusion Criteria:

* The presence of any of the following will exclude a subject from study enrollment: Any chronic liver disease other than NASH (i.e., drug-induced, viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, A1AT deficiency, Wilsons disease)
* Cirrhosis, as assessed clinically or histologically
* Presence of vascular liver disease
* BMI ≤ 25 kg/m2
* Excessive alcohol use (\> 20 g/day) within the past 2 years
* AST or ALT \> 250 U/L.
* Type 1 diabetes mellitus
* Bariatric surgery in the past 5 years.
* Weight gain of \> 5% in past 6 months or \> 10% change in past 12 months.
* Inadequate venous access
* HIV antibody positive, hepatitis B surface antigen positive (HBsAg), or HCV RNA positive.
* Receiving an elemental diet or parenteral nutrition
* Chronic pancreatitis or pancreatic insufficiency
* Any history of complications of cirrhosis (i.e. ascites, hepatic encephalopathy, or portal hypertensive bleeding), even if absent or optimized with medical management at time of screening
* Concurrent conditions: a) Inflammatory bowel disease, b) Unstable angina, myocardial infarction, transient ischemic events, or stroke within 24 weeks of screening, c) Ongoing infectious, immune mediated disease within previously 1 years, d) Any malignant disease (other than basal cell carcinoma of the skin) within previous 5 years, e) Prior solid organ transplant, f) Any other concurrent condition which, in the opinion of the investigator, could impact adversely on the subject participating or the interpretation of the study data.
* Concurrent medications including: a) Anti-NASH therapy(s) initiated after the liver biopsy diagnosing NASH. Anti-NASH therapies include S-adenosyl methionine (SAMe), milk thistle, and vitamin E at dose of ≥ 400 IU/day; b) Antidiabetic mediation which may impact NASH histology started in the past 12 months including thiazolidinediones (glitazones), dipeptidyl peptidase 4 inhibitors (gliptins) or glucagon-like peptide 1 analogs; c) Immune modulatory agents including systemic steroids, methotrexate, anti-TNF-α therapies (infliximab, adalimumab, etanercept) or anti-integrin therapy (namixilab).
* Self-reported or known marijuana or illicit drug use 30 days before the screening
* The following laboratory abnormalities within 90 days of screening: a) HbA1C \> 9.0%, b) Neutrophil count \< 1.0 x 109/L, c) Platelets \< 100 109/L, d) Hemoglobin \< 10 g/dl, e) Albumin \< 3.5 g, f) Prolonged international normalized ratio (INR), g) Any elevation of bilirubin above normal (unless Gilbert's syndrome or extrahepatic source as denoted by increased indirect bilirubin fraction), h) Serum creatinine \> 1.5 mg/dl, i) Creatinine clearance ≤ 50 ml/minute calculated by Crockroft-Gault or creatinine \> 1.5x upper limit of normal
* Pregnancy or breastfeeding.
* Women, of childbearing age, who are not willing to practice effective contraception (i.e., barrier, oral contraceptives, or past medical history of hysterectomy) for the 48-week duration of the trial and for 1 month after the first administration of the drug.
* Participation in an investigational drug study within past 3 months.

Where this trial is running

Rochester, Minnesota and 1 other locations

• Mayo Clinic Minnesota — Rochester, Minnesota, United States (Recruiting)
• Duke University Medical Center — Durham, North Carolina, United States (Active_not_recruiting)

Study contacts

• Principal investigator: Manal Abdelmalek, MD, MPH — Mayo Clinic
• Study coordinator: Christopher Kigongo

Conditions NASH - Nonalcoholic Steatohepatitis