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Vitamin E for NASH Treatment in HIV Infected Individuals

Primary Purpose

NAFLD, NASH - Nonalcoholic Steatohepatitis, HIV Infections

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Vitamin E

Placebo

About this trial

This is an interventional treatment trial for NAFLD focused on measuring Fatty liver, NAFLD, NASH, HIV, Vitamin E

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Indiana University School of Medicine
Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Group A

Group B

Arm Description

Vitamin E 800 IU/daily for 24 weeks

Matching placebo for 24 weeks

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

Full Information

NCT ID

NCT03669133

First Posted

September 5, 2018

Last Updated

July 3, 2023

Sponsor

Indiana University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT03669133

Brief Title

Vitamin E for NASH Treatment in HIV Infected Individuals

Official Title

Vitamin E for NASH Treatment in HIV Infected Individuals

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Terminated

Why Stopped

lack of coordinator resources and lack of access to study resources during and due to the COVID pandemic

Study Start Date

October 1, 2019 (Actual)

Primary Completion Date

March 8, 2021 (Actual)

Study Completion Date

March 8, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Indiana University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NAFLD, NASH - Nonalcoholic Steatohepatitis, HIV Infections

Keywords

Fatty liver, NAFLD, NASH, HIV, Vitamin E

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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)

Masking

ParticipantCare ProviderInvestigator

Masking Description

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

Allocation

Randomized

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A

Arm Type

Active Comparator

Arm Description

Vitamin E 800 IU/daily for 24 weeks

Arm Title

Group B

Arm Type

Placebo Comparator

Arm Description

Matching placebo for 24 weeks

Intervention Type

Drug

Intervention Name(s)

Vitamin E

Intervention Description

Vitamin E 800 IU/daily

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo daily

Primary Outcome Measure Information:

Title

Percent Change in Liver Fat Content by Magnetic Resonance Proton-Density Fat Fraction

Description

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)

Secondary Outcome Measure Information:

Title

Impact of Vitamin E Treatment on Noninvasive Markers of Hepatic Fibrosis

Description

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)

Title

Impact of Treatment on ALT as a Noninvasive Marker of Hepatic Inflammation

Description

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)

Title

Impact of Treatment on AST as a Noninvasive Marker of Hepatic Inflammation

Description

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Indiana University School of Medicine

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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