Effectiveness of Nucleoside Supplementation and Substituting Tenofovir Disoproxil Fumarate for Other Drugs in Anti-HIV Regimens in Reversing Fat Loss in HIV Infected Adults

HIV Infections Clinical Trial

Official title:

Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00119379
• Other study ID #: 1R01AI060484-01A2B
• Secondary ID: 1R01AI060484-01A
• Status: Completed
• Phase: Phase 2
• First received: July 11, 2005
• Last updated: September 22, 2016
• Start date: April 2005
• Est. completion date: October 2008

Study information

• Verified date: August 2007
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Lipodystrophy
• Metabolic Diseases
• Nutrition Disorders

Intervention

Drug:
• NucleomaxX
NucleomaxX 36 grams TID every other day
• Tenofovir disoproxil fumarate
Switch thymidine NRTI to tenofovir

Locations

Country	Name	City	State
United States	University Hospitals of Cleveland	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Epub 2007 May 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in mtDNA content		48 weeks	No
Primary	changes in mitochondrial function		48 weeks	No
Secondary	Changes in fat apoptosis		48 weeks	No
Secondary	changes in oxidative damage biomarkers		48 weeks	No

External Links

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