Clinical trial NCT03669133: Vitamin E for NASH Treatment in HIV Infected Individuals
Official title: Vitamin E for NASH Treatment in HIV Infected Individuals
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: NAFLD
NASH - Nonalcoholic Steatohepatitis
HIV Infections
Keywords: Fatty liver
NAFLD
NASH
HIV
Vitamin E
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2018-09-13
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change in Liver Fat Content by Magnetic Resonance Proton-Density Fat Fraction
timeFrame: at randomization visit (study day 1) and end of study visit (week 24)
Secondary outcomes:
measure: Impact of Vitamin E Treatment on Noninvasive Markers of Hepatic Fibrosis
timeFrame: change from baseline (first screening visit) to the end of study visit (week 24)
measure: Impact of Treatment on ALT as a Noninvasive Marker of Hepatic Inflammation
timeFrame: at randomization visit (study day 1) and end of study visit (week 24)
measure: Impact of Treatment on AST as a Noninvasive Marker of Hepatic Inflammation
timeFrame: Change in AST from study randomization (day 1) through the end of study visit (week 24)
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References: