Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults
Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy
2 other identifiers
interventional
50
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 hiv-infections
Started Apr 2005
Typical duration for phase_2 hiv-infections
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2005
CompletedFirst Submitted
Initial submission to the registry
July 11, 2005
CompletedFirst Posted
Study publicly available on registry
July 13, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2008
CompletedResults Posted
Study results publicly available
May 12, 2017
CompletedJune 7, 2017
May 1, 2017
3.5 years
July 11, 2005
December 8, 2016
May 15, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change in Fat mtDNA Content
Subcutaneous abdominal fat mitochondrial DNA (mtDNA)
Baseline to Week 48
Change in PBMC mtDNA
Peripheral blood mononuclear cell (PBMC) mitochondrial DNA (mtDNA), measured in copies/cell
Baseline to Week 48
Secondary Outcomes (4)
Change in Limb Fat
Baseline to Week 48
Change in Trunk Fat
Baseline to Week 48
Change in Lumbar Spine Bone Mineral Density (BMD)
Baseline to Week 48
Change in Hip Bone Mineral Density (BMD)
Baseline to Week 48
Study Arms (2)
uridine supplementation
EXPERIMENTALNucleomaxX 36 grams TID every other day
Switch to Tenofovir
ACTIVE COMPARATORSwitch of AZT or d4T to Tenofovir Disoproxil Fumarate
Interventions
Switch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate
Eligibility Criteria
You may qualify if:
- Diagnosis of HIV lipoatrophy
- Receiving a stable stavudine- or zidovudine-containing ARV regimen
- HIV-1 RNA viral load less than 50 copies/ml
You may not qualify if:
- Coagulopathies or other bleeding disorders
- Diabetes requiring medication
- Creatinine clearance less than 50 ml/min
- Pregnancy or breastfeeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University Hospitals of Cleveland
Cleveland, Ohio, 44106, United States
Related Publications (2)
McComsey GA, O'Riordan M, Setzer B, Lebrecht D, Baron E, Walker UA. Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices. Eur J Clin Nutr. 2008 Aug;62(8):1031-7. doi: 10.1038/sj.ejcn.1602793. Epub 2007 May 30.
PMID: 17538545RESULTMcComsey GA, O'Riordan M, Choi J, Libutti D, Rowe D, Storer N, Harrill D, Gerschenson M. Mitochondrial function, inflammation, fat and bone in HIV lipoatrophy: randomized study of uridine supplementation or switch to tenofovir. Antivir Ther. 2012;17(2):347-53. doi: 10.3851/IMP1928. Epub 2011 Oct 13.
PMID: 22293126DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Small sample size; Lack of control arm where tNRTI therapy was continued without any intervention; Adherence measured by sachet/pill count method.
Results Point of Contact
- Title
- Dr. Grace McComsey
- Organization
- University Hospitals Case Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Grace A. McComsey, MD
Case Western Reserve University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 11, 2005
First Posted
July 13, 2005
Study Start
April 1, 2005
Primary Completion
October 1, 2008
Study Completion
October 1, 2008
Last Updated
June 7, 2017
Results First Posted
May 12, 2017
Record last verified: 2017-05
Data Sharing
- IPD Sharing
- Will not share