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Completed

NCT Number: NCT00119379

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

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.

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Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections Lipid Metabolism Disorders Lipodystrophy Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Skin Diseases Skin Diseases, Metabolic Skin and Connective Tissue Diseases Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

NucleomaxX

Drug

NucleomaxX 36 grams TID every other day

Other names: uridine

Tenofovir disoproxil fumarate

Drug

Switch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate

Other names: TDF

Primary outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Nih

Registry information

Official study title

Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy

Important dates

Study start
2005
Primary completion
2008
Study completion
2008
First posted
Jul 13, 2005
Registry last updated
Jun 7, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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