- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00575757
Relationship of Metabolic Abnormalities to Hepatic Steatosis in HIV
August 17, 2016 updated by: Virginia Commonwealth University
Because NASH is now recognized as a significant cause of cirrhosis with associated morbidity and mortality, its recognition as a long term complication of HAART is important to the management of those living with HIV.
Study Overview
Status
Completed
Conditions
Detailed Description
Abnormal liver enzymes are frequently seen in those with HIV.
Although many of these individuals are co-infected with HBV or HCV, histology in HIV patients with abnormal liver enzymes in the absence of viral hepatitis has not been explored.
HAART has significantly improved the survival in those living with HIV.
However, components of HAART, particularly protease inhibitors (PIs) and certain nucleoside reverse transcriptase inhibitors (NRTIs), are frequently associated with metabolic abnormalities including insulin resistance (IR), dyslipidemias, fat redistribution and lipodystrophy (LD).
Both IR and dyslipidemia are pathogenic mechanisms associated with nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) which often present as asymptomatic liver enzyme elevations.
Because NASH is now recognized as a significant cause of cirrhosis with associated morbidity and mortality, its recognition as a long term complication of HAART is important to the management of those living with HIV.
In our HIV population without HCV or HBV, there is a higher prevalence of abnormal liver enzymes (AST 21%, ALT 16%, ALP 43%) compared to the general population (ALT 8%) and is independently associated with PI use.
The relationship of liver enzyme abnormalities to IR, dyslipidemias, and the development hepatic steatosis/NASH in HIV patients is unknown.
We hypothesize that Liver enzyme abnormalities in HIV positive patients without viral hepatitis co-infections on HAART are due to hepatic steatosis related to PI use and that a subset of these individuals has NASH.
The Specific Aims focus on HIV positive patients with abnormal liver enzymes in the absence of viral hepatitis co-infections, diabetes, or alcohol abuse to answer the following three questions: (1) What is the spectrum of NAFLD?; (2) How does the spectrum compare in those that are on a PI compare to those that are not; and (3) What are the independent predictive factors associated with hepatic steatosis and NASH?
These studies will (1) provide novel data on the histology of HIV infected patients with abnormal liver enzymes in the absence of viral coinfections and their relationship to IR, LD, dyslipidemias, and HAART use and (2) provide the necessary pilot data for a multicenter R0-1 grant to study the long-term impact of HAART on the development of steatohepatitis and subsequent hepatic fibrosis.
Study Type
Observational
Enrollment (Actual)
12
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Virginia
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Richmond, Virginia, United States, 23298
- Virgnia Commonwealth University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
HIV positive with abnormal liver enzymes in the absence of HCV/HBV coinfections.
Description
Inclusion Criteria:
- HIV antibody positive.
- Age > 18 years
- Abnormal liver chemistries (AST, ALT, and/or ALP) defined as between 1.25 -5 x ULN.
Exclusion Criteria:
- Hepatic decompensation: coagulopathy (prothrombin time prolonged > 2 seconds, INR > 1.5), ascites, hepatic encephalopathy, jaundice (serum conjugated bilirubin > 3.0)
- Thrombocytopenia (platelets < 80,000)
- Use of vitamin E, thiazolidinediones, metformin
- Use of medications associated with steatosis: amiodarone, methotrexate, corticosteroids, estrogen, and tamoxifen
- Renal failure (serum creatinine > 3.0)
- Diabetes mellitus
- Advanced HIV disease with life expectancy less than 1 year
- Alcohol use (> 40 grams/day in men and 20 grams/day in women)
- Presence of HCV RNA or HBV surface antigen
- Other liver diseases including alpha-1 antitrypsin (A1AT) deficiency, autoimmune hepatitis, hemochromatosis, Wilson's disease, HIV cholangiopathy, bacillary angiomatosis, lymphoma, and Kaposi's sarcoma
- Inability to give informed consent.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Primary
HIV infected with abnormal liver enzymes in the absence of HCV or HBV coinfections.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
What is the spectrum of NAFLD in HIV
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
How does the spectrum compare in those that are on a PI compare to those that are not.
Time Frame: 2 years
|
2 years
|
What are the independent predictive factors associated with hepatic steatosis and NASH?
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Richard K Sterling, MD MSc, VCU
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2007
Primary Completion (Actual)
July 1, 2016
Study Completion (Actual)
July 1, 2016
Study Registration Dates
First Submitted
December 14, 2007
First Submitted That Met QC Criteria
December 17, 2007
First Posted (Estimate)
December 18, 2007
Study Record Updates
Last Update Posted (Estimate)
August 18, 2016
Last Update Submitted That Met QC Criteria
August 17, 2016
Last Verified
August 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- VCUHM10107
- 1R03DK075416-01 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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