Vitamin E for NASH Treatment in HIV Infected Individuals

Sponsor

Indiana University School of Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT03669133

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
NAFLD NASH - Nonalcoholic Steatohepatitis HIV Infections	Drug: Vitamin E Drug: Placebos	Phase 2

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.

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 Design

Study Type:

Interventional

Anticipated Enrollment :

56 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Group A: Vitamin E 800 IU/daily for 24 weeks. (total of 28 subjects) Group B: Matching placebo for 24 weeks (total of 28 subjects)Group A: Vitamin E 800 IU/daily for 24 weeks. (total of 28 subjects) Group B: Matching placebo for 24 weeks (total of 28 subjects)

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Study biostatistician and Investigational Drug Services pharmacist will randomize subjects and will provide study drug

Primary Purpose:

Treatment

Official Title:

Vitamin E for NASH Treatment in HIV Infected Individuals

Actual Study Start Date :

Dec 1, 2019

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

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: Placebos Matching placebo daily

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: Placebos

Matching placebo daily

Outcome Measures

Primary Outcome Measures

Measure % 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)]
MRI at randomization and completion visits to assess liver steatosis

Secondary Outcome Measures

Determine the impact of vitamin E treatment on noninvasive markers of hepatic inflammation [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 [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 [at randomization visit (study day 1) and end of study visit (week 24)]
liver stiffness by fibroscan (kPa)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

males and females ≥18 years with biopsy-proven NASH within 6 months prior to enrollment
histological diagnosis of NASH will be confirmed by an experienced liver pathologist before study entry
HIV infection
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
willingness to participate in the study
ability to understand and give informed consent for participation

Exclusion Criteria:

Presence of other chronic liver diseases (hepatitis B or C, autoimmune hepatitis, cholestatic liver disease, Wilson disease, hemochromatosis, etc.)
average alcohol consumption >3 drinks/day for men or >2 drinks/day for women in the 6 months prior to enrollment.
Alcohol Use Disorder Identification Test (AUDIT) score of ≥8
evidence of cirrhosis on histology or imaging
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)
prior bariatric surgery
severe co-morbidities (e.g., advanced cardiac, renal, pulmonary, or psychiatric illness)
allergy to vitamin E
use of vitamin E or multivitamins containing vitamin E in the three months preceding enrollment
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.
changing doses of statins (simvastatin, pravastatin, atorvastatin, fluvastatin, lovastatin, rosuvastatin) or fibrates (clofibrate, fenofibrate) in the three months prior enrollment.
illicit substance abuse within the past twelve months
breast feeding, pregnancy, inability or unwillingness to practice contraception for the duration of the study
contraindications for the MRI procedure (e.g., prostheses, severe claustrophobia)
poorly controlled diabetes with A1C >8.5 within in the last six months
use of total parenteral nutrition in the 6 months preceding liver biopsy or enrollment