NCT04679376Active, not recruitingPhase 2
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)
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Mayo Clinic
- Enrollment
- 70
- Locations
- 2
- Primary Endpoint
- Change in NASH as measured by improvement in NAS score Improvement in NAS score (≥ 2 points) with no worsening in fibrosis stage (≥1 point) OR improvement in fibrosis with no worsening of NASH (change in the NAS score of ≤ 0 points).
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Group 1: Atorvastatin Treatment
Experimental
Subjects who have a histology-proved NASH with fibrosis stage 2 or higher will receive atorvastatin for 96 weeks
Intervention: Atorvastatin (Drug)
Group 2: Placebo
Placebo Comparator
Subjects who have a histology-proved NASH with fibrosis stage 2 or higher will receive a placebo for 96 weeks
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in NASH as measured by improvement in NAS score Improvement in NAS score (≥ 2 points) with no worsening in fibrosis stage (≥1 point) OR improvement in fibrosis with no worsening of NASH (change in the NAS score of ≤ 0 points).
Time Frame: Baseline, 96 weeks
One overall score of NASH improvement will be derived from improvement in NAS score OR no worsening in fibrosis.
Secondary Outcomes
- NASH resolution as measured by (diagnosis by pathologist) (from definite- to not- NASH).....(Baseline, 96 weeks)
- Change in fibrosis stage as measured by change in stage(Baseline, 96 weeks)
- Change in each component of NASH histologic features as measured by presence or ab presence or absence of features or their severity.(Baseline, 96 weeks)
- Change in serum aminotransferase (ALT) and aspartate aminotransferase (AST) levels as measured by plasma concentrations(Baseline, 96 weeks)
- Change in makers of hepatic fibrosis markers as measured by (FIB-4,51 liver stiffness by Fibroscan®)(Baseline, 96 weeks)
- Change in capture attention parameter (CAP) score (with Fibroscan®)(Baseline, 96 weeks)
- Serum creatine phosphokinase (CPK) as measured by serum concentration(Baseline, 96 weeks)
- Change in serum lipids as measured by serum concentration(Baseline, 96 weeks)
Investigators
Manal F. Abdelmalek
Principal Investigator
Mayo Clinic
Study Sites (2)
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