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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00119379
Recruitment Status : Completed
First Posted : July 13, 2005
Results First Posted : May 12, 2017
Last Update Posted : June 7, 2017
Information provided by (Responsible Party):
Grace McComsey, Case Western Reserve University

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
HIV Infections Lipodystrophy Metabolic Diseases Nutrition Disorders Drug: NucleomaxX Drug: Tenofovir Disoproxil Fumarate Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy
Study Start Date : April 2005
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: uridine supplementation
NucleomaxX 36 grams TID every other day
Drug: NucleomaxX
NucleomaxX 36 grams TID every other day
Other Name: uridine

Active Comparator: Switch to Tenofovir
Switch of AZT or d4T to Tenofovir Disoproxil Fumarate
Drug: Tenofovir Disoproxil Fumarate
Switch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate
Other Name: TDF

Primary Outcome Measures :
  1. Change in Fat mtDNA Content [ Time Frame: Baseline to Week 48 ]
    Subcutaneous abdominal fat mitochondrial DNA (mtDNA)

  2. Change in PBMC mtDNA [ Time Frame: Baseline to Week 48 ]
    Peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA), measured in copies/cell

Secondary Outcome Measures :
  1. Change in Limb Fat [ Time Frame: Baseline to Week 48 ]
    Change in limb fat as measured by dual-energy x-ray absorbtiometry (DEXA) scan

  2. Change in Trunk Fat [ Time Frame: Baseline to Week 48 ]
    Change in trunk fat as measured by dual-energy x-ray absorbtiometry (DEXA) scan

  3. 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

  4. 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00119379

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United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Grace A. McComsey, MD Case Western Reserve University
Additional Information:
Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Grace McComsey, Principal Investigator, Case Western Reserve University Identifier: NCT00119379    
Other Study ID Numbers: 1R01AI060484-01A2B
R01AI060484 ( U.S. NIH Grant/Contract )
First Posted: July 13, 2005    Key Record Dates
Results First Posted: May 12, 2017
Last Update Posted: June 7, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Grace McComsey, Case Western Reserve University:
treatment experienced
Additional relevant MeSH terms:
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Metabolic Diseases
Nutrition Disorders
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents