Vitamin E for NASH Treatment in HIV Infected Individuals

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 Overview

• Status: Terminated
• Conditions: HIV Infections; NAFLD; NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Drug: Vitamin E; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; Vitamin E 800 IU/daily for 24 weeks	Drug: Vitamin E; Vitamin E 800 IU/daily
Placebo Comparator: Group B; Matching placebo for 24 weeks	Drug: Placebo; Matching placebo daily

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of Vitamin E Treatment on Noninvasive Markers of Hepatic Fibrosis	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	change from baseline (first screening visit) to the end of study visit (week 24)
Impact of Treatment on ALT as a Noninvasive Marker of Hepatic Inflammation	This measure reflects the change in ALT(IU/L) value for study participants at two study time points	at randomization visit (study day 1) and end of study visit (week 24)
Impact of Treatment on AST as a Noninvasive Marker of Hepatic Inflammation	This measure reflects the change in AST(IU/L) value for study participants at two study time points	Change in AST from study randomization (day 1) through the end of study visit (week 24)

Collaborators and Investigators

• Sponsor: Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): March 8, 2021
• Study Completion (Actual): March 8, 2021

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: HIV; Vitamin E; NAFLD; NASH; Fatty liver
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E
• Other Study ID Numbers: 1807274844

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: Yes