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Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grace McComsey, Case Western Reserve University
ClinicalTrials.gov Identifier:
NCT00119379
First received: July 11, 2005
Last updated: May 15, 2017
Last verified: May 2017
July 11, 2005
May 15, 2017
April 2005
October 2008   (Final data collection date for primary outcome measure)
  • Change in Fat mtDNA Content [ Time Frame: Baseline to Week 48 ]
    Subcutaneous abdominal fat mitochondrial DNA (mtDNA)
  • Change in PBMC mtDNA [ Time Frame: Baseline to Week 48 ]
    Peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA), measured in copies/cell
  • Changes in mtDNA content
  • changes in mitochondrial function
Complete list of historical versions of study NCT00119379 on ClinicalTrials.gov Archive Site
  • Change in Limb Fat [ Time Frame: Baseline to Week 48 ]
    Change in limb fat as measured by dual-energy x-ray absorbtiometry (DEXA) scan
  • Change in Trunk Fat [ Time Frame: Baseline to Week 48 ]
    Change in trunk fat as measured by dual-energy x-ray absorbtiometry (DEXA) scan
  • Change in Lumbar Spine Bone Mineral Density (BMD) [ Time Frame: Baseline to Week 48 ]
    Change in lumbar spine bone mineral density (BMD) as measured by dual-energy x-ray absorbtiometry (DEXA) scan
  • Change in Hip Bone Mineral Density (BMD) [ Time Frame: Baseline to Week 48 ]
    Change in hip bone mineral density (BMD) as measured by dual-energy x-ray absorbtiometry (DEXA) scan
  • Changes in fat apoptosis
  • changes in oxidative damage biomarkers
Not Provided
Not Provided
 
Effectiveness of Nucleoside Supplementation or Switch to Tenofovir 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
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • HIV Infections
  • Lipodystrophy
  • Metabolic Diseases
  • Nutrition Disorders
  • Drug: NucleomaxX
    NucleomaxX 36 grams TID every other day
    Other Name: uridine
  • Drug: Tenofovir Disoproxil Fumarate
    Switch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate
    Other Name: TDF
  • Experimental: uridine supplementation
    NucleomaxX 36 grams TID every other day
    Intervention: Drug: NucleomaxX
  • Active Comparator: Switch to Tenofovir
    Switch of AZT or d4T to Tenofovir Disoproxil Fumarate
    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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00119379
1R01AI060484-01A2B
R01AI060484 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Plan to Share IPD: No
Grace McComsey, 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)
May 2017

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