Clinical trial NCT04679376: Statins for the Treatment of NASH
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: NASH - Nonalcoholic Steatohepatitis
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2020-12-22
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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).
timeFrame: Baseline, 96 weeks
Secondary outcomes:
measure: NASH resolution as measured by (diagnosis by pathologist) (from definite- to not- NASH).....
timeFrame: Baseline, 96 weeks
measure: Change in fibrosis stage as measured by change in stage
timeFrame: Baseline, 96 weeks
measure: Change in each component of NASH histologic features as measured by presence or ab presence or absence of features or their severity.
timeFrame: Baseline, 96 weeks
measure: Change in serum aminotransferase (ALT) and aspartate aminotransferase (AST) levels as measured by plasma concentrations
timeFrame: Baseline, 96 weeks
measure: Change in makers of hepatic fibrosis markers as measured by (FIB-4,51 liver stiffness by Fibroscan®)
timeFrame: Baseline, 96 weeks
measure: Change in capture attention parameter (CAP) score (with Fibroscan®)
timeFrame: Baseline, 96 weeks
measure: Serum creatine phosphokinase (CPK) as measured by serum concentration
timeFrame: Baseline, 96 weeks
measure: Change in serum lipids as measured by serum concentration
timeFrame: Baseline, 96 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Minnesota
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Mayo Clinic
name: Manal Abdelmalek, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: