Vitamin E for NASH Treatment in HIV Infected Individuals

Overview

The purpose of this study is to see how taking Vitamin E daily affects fatty liver in persons living with HIV. Subjects will have both HIV and a fatty liver and the purpose of the study is to learn if underlying liver condition (fatty liver) gets better, worse, or stays the same from taking Vitamin E.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: December 31, 2022

Detailed Description

The investigators will conduct a proof-of-concept clinical trial to evaluate the efficacy of vitamin E for treatment of non-alcoholic steatohepatitis (NASH) in persons living with HIV. Hypothesis: Vitamin E will improve radiographically measured hepatic fat content and circulating markers of liver inflammation and injury in persons living with HIV who have NASH.

A. Perform a pilot randomized placebo controlled trial of vitamin E 800 IU/daily for 6 months in 56 persons living with HIV with biopsy-proven NASH B. Measure change in liver fat content by magnetic resonance proton-density fat fraction (Primary outcome) C. Determine the impact of vitamin E treatment on noninvasive markers of hepatic and systemic inflammation, hepatic fibrosis, and systemic oxidative stress (Secondary outcomes) D. Define baseline hepatic gene expression signatures predictive of response to therapy.

Upon completion, the proposed clinical trial may establish vitamin E as an excellent and inexpensive candidate for further development as a treatment for NASH in persons living with HIV.

Interventions

  • Drug: Vitamin E
    • Vitamin E 800 IU/daily
  • Drug: Placebos
    • Matching placebo daily

Arms, Groups and Cohorts

  • Active Comparator: Group A
    • Vitamin E 800 IU/daily for 24 weeks
  • Placebo Comparator: Group B
    • Matching placebo for 24 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Measure % change in liver fat content by magnetic resonance proton-density fat fraction
    • Time Frame: at randomization visit (study day 1) and end of study visit (week 24)
    • MRI at randomization and completion visits to assess liver steatosis

Secondary Measures

  • Determine the impact of vitamin E treatment on noninvasive markers of hepatic inflammation
    • Time Frame: at randomization visit (study day 1) and end of study visit (week 24)
    • ALT(IU/L), AST (IU/L) , cytokeratin-18 (IU/L).
  • Determine the impact of vitamin E treatment on noninvasive markers of systemic inflammation
    • Time Frame: at randomization visit (study day 1) and end of study visit (week 24)
    • TNF-alpha (pg/L), IL-10 (pg/L)
  • Determine the impact of vitamin E treatment on noninvasive markers of hepatic fibrosis
    • Time Frame: at randomization visit (study day 1) and end of study visit (week 24)
    • liver stiffness by fibroscan (kPa)

Participating in This Clinical Trial

Inclusion Criteria

1. males and females ≥18 years with biopsy-proven NASH within 6 months prior to enrollment

2. histological diagnosis of NASH will be confirmed by an experienced liver pathologist before study entry

3. HIV infection

4. stable dose of anti-diabetic agents and ART in the 3 months preceding enrollment and expected by the physician treating diabetes and HIV to remain on stable medications during the study

5. willingness to participate in the study

6. ability to understand and give informed consent for participation

Exclusion Criteria

1. Presence of other chronic liver diseases (hepatitis B or C, autoimmune hepatitis, cholestatic liver disease, Wilson disease, hemochromatosis, etc.)

2. average alcohol consumption >3 drinks/day for men or >2 drinks/day for women in the 6 months prior to enrollment.

3. Alcohol Use Disorder Identification Test (AUDIT) score of ≥8

4. evidence of cirrhosis on histology or imaging

5. ongoing use of medications known to cause hepatic steatosis (e.g., corticosteroids, amiodarone, methotrexate, tetracycline, tamoxifen, estrogens at doses greater than those used for birth control, anabolic steroids, or valproic acid)

6. prior bariatric surgery

7. severe co-morbidities (e.g., advanced cardiac, renal, pulmonary, or psychiatric illness)

8. allergy to vitamin E

9. use of vitamin E or multivitamins containing vitamin E in the three months preceding enrollment

10. use of drugs with potential effect on NASH such as ursodeoxycholic acid, S-adenosylmethionine (SAM-e), betaine, pentoxifylline, or milk thistle in the three months prior to enrollment.

11. changing doses of statins (simvastatin, pravastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin) or fibrates (clofibrate, fenofibrate) in the three months prior enrollment.

12. illicit substance abuse within the past twelve months

13. breast feeding, pregnancy, inability or unwillingness to practice contraception for the duration of the study

14. contraindications for the MRI procedure (e.g., prostheses, severe claustrophobia)

15. poorly controlled diabetes with A1C >8.5 within in the last six months

16. use of total parenteral nutrition in the 6 months preceding liver biopsy or enrollment

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Indiana University School of Medicine
  • Provider of Information About this Clinical Study
    • Principal Investigator: Samer Gawrieh, Associate Professor of Medicine – Indiana University School of Medicine
  • Overall Contact(s)
    • Samer Gawrieh, MD, 317-278-9326, sgawrieh@iu.edu

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