Statins for the Treatment of NASH

Launched by MAYO CLINIC · Dec 17, 2020

Keywords

ClinConnect Summary

This clinical trial is studying the use of a medication called atorvastatin (often known by the brand name Lipitor®) to see if it can safely improve a liver condition called Nonalcoholic Steatohepatitis (NASH). NASH is a type of liver disease that occurs when there is too much fat in the liver, leading to inflammation and liver damage. The trial is currently recruiting participants aged between 65 and 74 years who have been diagnosed with definite NASH, confirmed through a liver biopsy, and have a certain level of liver damage but are not currently taking statin medications.

Eligible participants will be asked to commit to the study for about 48 weeks. They will need to provide written consent and agree to use effective birth control if they are women of childbearing age. Throughout the trial, participants will be monitored for any changes in their liver health and any side effects from the medication. This study is an important step in finding out if atorvastatin can help treat NASH, which currently has limited treatment options.

Gender

ALL

Eligibility criteria

• 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.