HIV Infections, NAFLD, NASH - Nonalcoholic Steatohepatitis
Conditions
Keywords
Fatty liver, NAFLD, NASH, HIV, Vitamin E
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.
Interventions
DRUGVitamin E
Vitamin E 800 IU/daily
DRUGPlacebo
Matching placebo daily
Sponsors
Indiana University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Study biostatistician and Investigational Drug Services pharmacist will randomize subjects and will provide study drug
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)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Pre-assignment details
3 participants consented to participate in this trial. One person screen-failed and two completed the trial, with one randomized to each arm.
Participants by arm
| Arm | Count |
|---|---|
| Group A Vitamin E 800 IU/daily for 24 weeks
Vitamin E: Vitamin E 800 IU/daily | 1 |
| Group B Matching placebo for 24 weeks
Placebos: Matching placebo daily | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Group A | Total | Group B |
|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 8.49 | 44 years STANDARD_DEVIATION 6 | 38 years STANDARD_DEVIATION 8.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
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
Time frame: at randomization visit (study day 1) and end of study visit (week 24)
Population: change in liver steatosis via MRI-PDFF or the one participant in each group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E 800 I/U | Percent Change in Liver Fat Content by Magnetic Resonance Proton-Density Fat Fraction | 0 percentage change |
| Placebo | Percent Change in Liver Fat Content by Magnetic Resonance Proton-Density Fat Fraction | 4 percentage change |
Secondary
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
Time frame: at randomization visit (study day 1) and end of study visit (week 24)
Population: Change in ALT from study randomization (day 1) through the end of study visit (week 24)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E 800 I/U | Impact of Treatment on ALT as a Noninvasive Marker of Hepatic Inflammation | -10 IU/L |
| Placebo | Impact of Treatment on ALT as a Noninvasive Marker of Hepatic Inflammation | 3 IU/L |
Secondary
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
Time frame: Change in AST from study randomization (day 1) through the end of study visit (week 24)
Population: one participant completed each group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E 800 I/U | Impact of Treatment on AST as a Noninvasive Marker of Hepatic Inflammation | -16 IU/L |
| Placebo | Impact of Treatment on AST as a Noninvasive Marker of Hepatic Inflammation | 14 IU/L |
Secondary
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
Time frame: change from baseline (first screening visit) to the end of study visit (week 24)
Population: Change in liver stiffness (LSM) via FibroScan for the one participant in each group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin E 800 I/U | Impact of Vitamin E Treatment on Noninvasive Markers of Hepatic Fibrosis | -28.3 kPa - kilopascels |
| Placebo | Impact of Vitamin E Treatment on Noninvasive Markers of Hepatic Fibrosis | -0.8 kPa - kilopascels |