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STAT NASH: Statins for the Treatment of NASH

Sponsor
Duke University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04679376
Collaborator
(none)
70
Enrollment
1
Location
2
Arms
28.7
Anticipated Duration (Months)
2.4
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Atorvastatin (40 mg daily)
  • Other: Placebo
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
70 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Aug 10, 2021
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group 1

Atorvastatin (40 mg daily)

Drug: Atorvastatin (40 mg daily)
administered in tablet or capsule form
Placebo Comparator: Group 2

Other: Placebo
administered in tablet or capsule form

Outcome Measures

Primary Outcome Measures

  1. 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). [Baseline, 96 weeks]

    One overall score of NASH improvement will be derived from improvement in NAS score OR no worsening in fibrosis.

Secondary Outcome Measures

  1. NASH resolution as measured by (diagnosis by pathologist) (from definite- to not- NASH)..... [Baseline, 96 weeks]

    Histological change from NASH to No NASH

  2. Change in fibrosis stage as measured by change in stage [Baseline, 96 weeks]

    Ordinal variable

  3. Change in each component of NASH histologic features as measured by presence or ab presence or absence of features or their severity. [Baseline, 96 weeks]

    Existing features may improve in severity or disappear as an indication of improvement of NASH.

  4. Change in serum aminotransferase (ALT) and aspartate aminotransferase (AST) levels as measured by plasma concentrations [Baseline, 96 weeks]

  5. Change in makers of hepatic fibrosis markers as measured by (FIB-4,51 liver stiffness by Fibroscan®) [Baseline, 96 weeks]

  6. Change in capture attention parameter (CAP) score (with Fibroscan®) [Baseline, 96 weeks]

  7. Serum creatine phosphokinase (CPK) as measured by serum concentration [Baseline, 96 weeks]

  8. Change in serum lipids as measured by serum concentration [Baseline, 96 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

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

  2. 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.

  3. 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:

  1. 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.

  1. Concurrent medications including:

  2. 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.

  3. 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.

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

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

  6. HbA1C > 9.0 %

  7. Neutrophil count < 1.0 x 109 / L

  8. Platelets < 100 109 / L

  9. Hemoglobin < 10 g/dl

  10. Albumin < 3.5 g

  11. Prolonged international normalized ratio (INR)

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

  13. Serum creatinine > 1.5 mg/dl

  14. 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.

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Duke University Medical Center Durham North Carolina United States 27710

Sponsors and Collaborators

  • Duke University

Investigators

  • Principal Investigator: Manal Abdelmalek, MD, Duke University
  • Principal Investigator: Ayako Suzuki, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Duke University
ClinicalTrials.gov Identifier:
NCT04679376
Other Study ID Numbers:
  • Pro00105745
First Posted:
Dec 22, 2020
Last Update Posted:
Sep 17, 2021
Last Verified:
Sep 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:
Fatty Liver
Non-alcoholic Fatty Liver Disease
Atorvastatin

Study Results

No Results Posted as of Sep 17, 2021