This site became the new on June 19th. Learn more.
Show more Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu
Give us feedback

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

This study has been completed.
Information provided by (Responsible Party):
Grace McComsey, Case Western Reserve University Identifier:
First received: July 11, 2005
Last updated: May 15, 2017
Last verified: May 2017

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 Intervention Phase
HIV Infections Lipodystrophy Metabolic Diseases Nutrition Disorders Drug: NucleomaxX Drug: Tenofovir Disoproxil Fumarate Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy

Resource links provided by NLM:

Further study details as provided by Grace McComsey, Case Western Reserve University:

Primary Outcome Measures:
  • 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

Secondary Outcome Measures:
  • 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

Enrollment: 50
Study Start Date: April 2005
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  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 identifier: NCT00119379

United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Grace A. McComsey, MD Case Western Reserve University
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Grace McComsey, Principal Investigator, Case Western Reserve University Identifier: NCT00119379     History of Changes
Other Study ID Numbers: 1R01AI060484-01A2B
R01AI060484 ( U.S. NIH Grant/Contract )
Study First Received: July 11, 2005
Results First Received: December 8, 2016
Last Updated: May 15, 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:
HIV Infections
Metabolic Diseases
Nutrition Disorders
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
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 processed this record on September 20, 2017