Statins for the Treatment of NASH (STAT NASH)

Mayo Clinic

Status and phase

Active, not recruiting

Phase 2

Conditions

NASH - Nonalcoholic Steatohepatitis

Treatments

Drug: Placebo

Drug: Atorvastatin

Study type

Interventional

Funder types

Other

Identifiers

NCT04679376

22-007824

Details and patient eligibility

About

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.

Enrollment

70 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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.