Observational Study of Fat Loss in HIV Infected Adults Taking Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2007 by National Institute of Allergy and Infectious Diseases (NIAID).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00119405
First received: July 11, 2005
Last updated: February 22, 2010
Last verified: December 2007
  Purpose

Nucleoside reverse transcriptase inhibitors (NRTIs) are a class of anti-HIV drug that can be an important part of an HIV treatment regimen. Because anti-HIV therapy may have negative side effects, there is a great need to carefully study HIV infected patients on such regimens. One negative side effect observed in many HIV infected patients is lipoatrophy, a condition that results in fat loss in the body. It is unclear if NRTIs also have a role in the development of mitochondrial toxicity, a condition that affects the body's ability to produce energy. The purpose of this study is to observe the effects of an NRTI-based, protease inhibitor (PI)-sparing drug regimen on fat loss in HIV infected, treatment-naive adults.

Study hypothesis: The initiation of NRTI-containing, PI-sparing therapy will inhibit mitochondrial DNA (mtDNA) synthesis and lead to a decrease in mtDNA content in adipose tissue, skeletal muscle and peripheral blood mononuclear cells (PBMCs), will cause deterioration in mitochondrial function, will increase fat apoptosis and oxidative damage biomarkers, and will lead to progressive decrease in body fat content.


Condition Phase
HIV Infections
Lipodystrophy
Metabolic Diseases
Nutrition Disorders
Phase 2

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Role of Mitochondria in the Development of HIV Atrophy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Mitochondrial function [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • mtDNA [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • fat apoptosis [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • limb fat [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • oxidative markers [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

Fat and Blood for mitochindrial DNA and different nuclear genes that regulate fat and lipid metabolism


Estimated Enrollment: 25
Study Start Date: April 2005
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Detailed Description:

NRTIs are a mainstay of HIV treatment regimens, often part of initial treatment regimens for newly diagnosed patients. Recent data suggest that NRTIs are responsible for lipoatrophy, a condition marked by progressive fat loss. Another negative side effect to antiretroviral (ARV) regimens is mitochondrial toxicity, which can damage the heart, nerves, muscles, kidneys, pancreas and liver, as well as affecting the body's ability to produce energy for important life processes. It has been hypothesized that lipoatrophy may be related to mitochondrial toxicity, but a causal relationship between the two has yet to be established. This study will examine HIV infected treatment-naive patients who are initiating their first ARV regimens. The regimens will contain 2 NRTI, one of which being zidovudine and a non-nucleoside reverse transcriptase inhibitor (NNRTI). The regimens will not contain any PIs.

Patients will participate in this study for 96 weeks. There will be 4 study visits at Weeks 12, 24, 48, and 96. Dual-energy x-ray absorptiometry (DEXA) scans and fat biopsies will occur at all visits. Additionally, blood collection for metabolic testing will occur at Week 12. ARVs will not be provided by this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV positive adults starting their first antiretroviral regimen with either AZT-containing combination

Criteria

Inclusion Criteria:

  • HIV-1 infected
  • Treatment-naive
  • Plan to initiate first ARV regimen with 2 NRTIs and an NNRTI
  • Plan to include zidovudine as part of first ARV regimen

Exclusion Criteria:

  • Current use of steroids or growth hormone
  • Coagulopathies or other bleeding disorders
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00119405

Locations
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Principal Investigator: Grace A. McComsey, MD University Hospitals of Cleveland
  More Information

Additional Information:
No publications provided

Responsible Party: Grace McComsey, MD, Case Western Reserve University
ClinicalTrials.gov Identifier: NCT00119405     History of Changes
Other Study ID Numbers: 1R01AI060484-01A2A, 1R01-AI060484-01A2A
Study First Received: July 11, 2005
Last Updated: February 22, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Lipoatrophy
Mitochondria
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lipodystrophy
Metabolic Diseases
Nutrition Disorders
Malnutrition
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2014