Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults
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|ClinicalTrials.gov Identifier: NCT00119379|
Recruitment Status : Completed
First Posted : July 13, 2005
Results First Posted : May 12, 2017
Last Update Posted : June 7, 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 or disease||Intervention/treatment||Phase|
|HIV Infections Lipodystrophy Metabolic Diseases Nutrition Disorders||Drug: NucleomaxX Drug: Tenofovir Disoproxil Fumarate||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
Experimental: uridine supplementation
NucleomaxX 36 grams TID every other day
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
- 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
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT00119379
|United States, Ohio|
|University Hospitals of Cleveland|
|Cleveland, Ohio, United States, 44106|
|Principal Investigator:||Grace A. McComsey, MD||Case Western Reserve University|