Statins for the Treatment of NASH

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

To conduct a double-blined randomized, placebo-controlled pilot study to evaluate the safety and efficacy of statin therapy (atorvastatin 40 mg daily) for the treatment of NASH and hepatic fibrosis.

The findings from this study will facilitate the design of a larger interventional study with proper consideration of biological disparities and eventually inform NASH treatment and personalized HCC chemoprevention approach using statins.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Treatments: Atorvastatin

Criteria

Inclusion Criteria:

1. Age ≥ 18 ≤ 70 years

2. 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

3. Fibrosis stage ≥ 2 as assessed by liver biopsy

4. Not currently on statin therapy

5. Provision of written informed consent

6. Agree to use of effective contraceptive measures if female of child bearing potential.

Exclusion Criteria:

• 1. 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) 2. Cirrhosis, as assessed clinically or histologically 3. Presence of vascular liver disease 4. BMI ≤ 25 kg/m2

5. Excessive alcohol use (> 20 g/day) within the past 2 years 6. AST or ALT > 250 U/L.

7. Type 1 diabetes mellitus 8. Bariatric surgery in the past 5 years. 9. Weight gain of > 5% in past 6 months or > 10% change in past 12 months. 10. Inadequate venous access 11. HIV antibody positive, hepatitis B surface antigen positive (HBsAg), or HCV RNA positive.

12. Receiving an elemental diet or parenteral nutrition 13. Chronic pancreatitis or pancreatic insufficiency 14. 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 15. 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.

16. Concurrent medications including:

1. 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.

2. 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.

3. Immune modulatory agents including systemic steroids, methotrexate, anti-TNF-α therapies (infliximab, adalimumab, etanercept) or anti-integrin therapy (namixilab).

17. Self-reported or known marijuana or illicit drug use 30 days before the screening 18. The following laboratory abnormalities within 90 days of screening:

1. HbA1C > 9.0 %

2. Neutrophil count < 1.0 x 109 / L

3. Platelets < 100 109 / L

4. Hemoglobin < 10 g/dl

5. Albumin < 3.5 g

6. Prolonged international normalized ratio (INR)

7. Any elevation of bilirubin above normal (unless Gilbert's syndrome or extrahepatic source as denoted by increased indirect bilirubin fraction).

8. Serum creatinine > 1.5 mg/dl

9. Creatinine clearance ≤ 50 ml/minute calculated by Crockroft-Gault or creatinine > 1.5x upper limit of normal 19. Pregnancy or breastfeeding. 20. 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.

21. Participation in an investigational drug study within past 3 months.