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Effectiveness of Nucleoside Supplementation and Substituting Tenofovir Disoproxil Fumarate for Other Drugs in Anti-HIV Regimens in Reversing Fat Loss in HIV Infected Adults

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00119379
First received: July 11, 2005
Last updated: February 22, 2010
Last verified: August 2007

July 11, 2005
February 22, 2010
April 2005
October 2008   (final data collection date for primary outcome measure)
  • Changes in mtDNA content [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • changes in mitochondrial function [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Changes in mtDNA content
  • changes in mitochondrial function
Complete list of historical versions of study NCT00119379 on ClinicalTrials.gov Archive Site
  • Changes in fat apoptosis [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • changes in oxidative damage biomarkers [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Changes in fat apoptosis
  • changes in oxidative damage biomarkers
Not Provided
Not Provided
 
Effectiveness of Nucleoside Supplementation and Substituting Tenofovir Disoproxil Fumarate for Other Drugs in Anti-HIV Regimens in Reversing Fat Loss in HIV Infected Adults
Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy

HIV lipoatrophy is a condition marked by fat loss; it occurs in many patients taking antiretroviral (ARV) therapy that includes nucleoside reverse transcriptase inhibitors (NRTIs). Lipoatrophy may be related to mitochondrial toxicity, a condition that can damage the heart, nerves, muscles, kidneys, and liver, and can affect the body's ability to produce energy. NucleomaxX is a food supplement consisting of a sugar cane extract high in nucleosides, which are building blocks that may counteract the negative effects of NRTIs. Tenofovir disoproxil fumarate (TDF) is an NRTI that may cause less lipoatrophy than other drugs in its class, such as zidovudine (ZDV) or stavudine (d4T). The purpose of this study is to determine whether nucleoside supplementation with NucleomaxX and substitution of TDF for ZDV or d4T in an ARV regimen can reverse fat loss caused by mitochondrial toxicity in HIV infected adults.

Study hypotheses: 1) The substitution of TDF for d4T or ZDV in patients with HIV lipoatrophy will result in an increase in mitochondrial DNA content in fat, skeletal muscle, and peripheral blood mononuclear cells (PBMCs), which in turn will lead to an improvement in mitochondrial function as assessed by electron transport chain (ETC) and oxidative phosphorylation pathway (OXPHOS) activity. The latter should lead to a decrease in fat apoptosis and in mitochondrial and lipid oxidative damage biomarkers. 2) Supplementation with uridine (via NucleomaxX) will increase mtDNA content in adipose tissue and increase body fat content.

NRTIs are an important part of many ARV regimens used to treat HIV infected patients; however, the relationship between NRTI-induced mitochondrial dysfunction and lipoatrophy is still unclear and requires additional research. Additionally, the relationship between the gain in dual-energy x-ray absorptiometry (DEXA)-measured limb fat and mitochondrial DNA (mtDNA) content, mitochondrial function, fat apoptosis, and oxidative damage will also be examined in this study.

Patients will participate in this study for 48 weeks. Participants will be randomly assigned to one of two groups. Group 1 patients will receive NucleomaxX every other day. Group 2 patients will substitute TDF for ZDV or d4T every day in their current stable NRTI-containing ARV regimen. NucleomaxX will be provided to Group 1 patients, but TDF or any other ARV will not be provided by this study.

There will be 10 study visits, which will occur at study entry and Weeks 2, 4, 8, 12, 18, 24, 30, 36, and 48. Blood collection will occur at all visits. Additionally, urine collection, DEXA scans, and fat biopsies will be done at study entry and Weeks 24 and 48.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infections
  • Lipodystrophy
  • Metabolic Diseases
  • Nutrition Disorders
  • Drug: NucleomaxX
    NucleomaxX 36 grams TID every other day
  • Drug: Tenofovir disoproxil fumarate
    Swicth thymidine NRTI to tenofovir
  • Experimental: 1
    NucleomaxX 36 grams TID every other day
    Intervention: Drug: NucleomaxX
  • Active Comparator: Switch
    Swicth of AZT or d4T to tenofovir
    Intervention: Drug: Tenofovir disoproxil fumarate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
October 2008
October 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of HIV lipoatrophy
  • Receiving a stable stavudine- or zidovudine-containing ARV regimen
  • HIV-1 RNA viral load less than 50 copies/ml

Exclusion Criteria:

  • Coagulopathies or other bleeding disorders
  • Diabetes requiring medication
  • Creatinine clearance less than 50 ml/min
  • Pregnancy or breastfeeding
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00119379
1R01AI060484-01A2B, 1R01-AI060484-01A2B
Yes
Grace McComsey, MD, Case Western Reserve University
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Principal Investigator: Grace A. McComsey, MD Case Western Reserve University
National Institute of Allergy and Infectious Diseases (NIAID)
August 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP