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

NCT ID: NCT00119379

Last Updated: 2017-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2008-10-31

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.

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.

Conditions

HIV Infections; Lipodystrophy; Metabolic Diseases; Nutrition Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

uridine supplementation

NucleomaxX 36 grams TID every other day

Group Type: EXPERIMENTAL

NucleomaxX

Intervention Type: DRUG

NucleomaxX 36 grams TID every other day

Switch to Tenofovir

Switch of AZT or d4T to Tenofovir Disoproxil Fumarate

Group Type: ACTIVE_COMPARATOR

Tenofovir Disoproxil Fumarate

Intervention Type: DRUG

Switch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate

Interventions

NucleomaxX

NucleomaxX 36 grams TID every other day

Intervention Type: DRUG

Tenofovir Disoproxil Fumarate

Switch of thymidine nucleoside reverse transcriptase inhibitors to Tenofovir Disoproxil Fumarate

Intervention Type: DRUG

Other Intervention Names

uridine; TDF

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Grace McComsey

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Grace A. McComsey, MD

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University

Locations

University Hospitals of Cleveland

Cleveland, Ohio, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 17538545 (View on PubMed)

McComsey 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.

Reference Type: DERIVED

PMID: 22293126 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/22293126/

click here for more information about uridine supplementation or switch to tenofovir.

Other Identifiers

R01AI060484

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01AI060484-01A2B

Identifier Type: -

Identifier Source: org_study_id