Statins for the Treatment of 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)

The purpose of this research study is to determine whether the study drug, atorvastatin (Lipitor®), is safe and effective in improving the features of NASH.

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.