Statins for the Treatment of NASH (STAT 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.

Study Overview

• Status: Recruiting
• Conditions: NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Atorvastatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christopher Kigongo; Phone Number: 507-266-1998; Email: Kigongo.Christopher@mayo.edu
• Study Contact Backup: Name: Amy Olofson; Phone Number: 507-538-6547; Email: Olofson.Amy@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Minnesota
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Active, not recruiting
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Atorvastatin Treatment; Subjects who have a histology-proved NASH with fibrosis stage 2 or higher will receive atorvastatin for 96 weeks	Drug: Atorvastatin; 40 mg daily administered orally in tablet or capsule form; Other Names: Lipitor
Placebo Comparator: Group 2: Placebo; Subjects who have a histology-proved NASH with fibrosis stage 2 or higher will receive a placebo for 96 weeks	Drug: Placebo; Administered daily orally in tablet or capsule form, contains no active medicine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	One overall score of NASH improvement will be derived from improvement in NAS score OR no worsening in fibrosis.	Baseline, 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NASH resolution as measured by (diagnosis by pathologist) (from definite- to not- NASH).....	Histological change from NASH to No NASH	Baseline, 96 weeks
Change in fibrosis stage as measured by change in stage	Ordinal variable	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.	Existing features may improve in severity or disappear as an indication of improvement of NASH.	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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Manal Abdelmalek, MD, MPH, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 17, 2020
• First Submitted That Met QC Criteria: December 17, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 22-007824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No