Vitamin E for NASH Treatment in HIV Infected Individuals

Phase 2

Terminated

• Conditions: NAFLD; NASH - Nonalcoholic Steatohepatitis; HIV Infections
• Interventions: Drug: Vitamin E; Drug: Placebo

• Registration Number: NCT03669133
• Lead Sponsor: Indiana University School of Medicine

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2018-09-05
• Study First Submitted QC: 2018-09-11
• Study First Posted: 2018-09-13
• Study Start: 2019-10-01
• Primary Completion: 2021-03-08
• Study Completion: 2021-03-08
• Results First Submitted: 2023-05-17
• Status Verified: 2023-07
• Results First Submitted QC: 2023-07-03
• Last Update Submitted: 2023-07-03
• Results First Posted: 2023-07-25
• Last Update Posted: 2023-07-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	Vitamin E	Vitamin E 800 IU/daily for 24 weeks
Group B	Placebo	Matching placebo for 24 weeks

Primary Outcome Measures

Name	Time	Method
Percent Change in Liver Fat Content by Magnetic Resonance Proton-Density Fat Fraction	at randomization visit (study day 1) and end of study visit (week 24)	change in liver steatosis via MRI-PDFF at randomization (day 1) and study completion (week 24) to assess liver steatosis

Secondary Outcome Measures

Name	Time	Method
Impact of Vitamin E Treatment on Noninvasive Markers of Hepatic Fibrosis	change from baseline (first screening visit) to the end of study visit (week 24)	This outcome measure reflects the change in liver stiffness in transient elastrography via FibroScan is measured in (kPa) for study participants at two study time points
Impact of Treatment on ALT as a Noninvasive Marker of Hepatic Inflammation	at randomization visit (study day 1) and end of study visit (week 24)	This measure reflects the change in ALT(IU/L) value for study participants at two study time points
Impact of Treatment on AST as a Noninvasive Marker of Hepatic Inflammation	Change in AST from study randomization (day 1) through the end of study visit (week 24)	This measure reflects the change in AST(IU/L) value for study participants at two study time points

Trial Locations

Locations (2)

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States