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

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00119379
First received: July 11, 2005
Last updated: February 22, 2010
Last verified: August 2007
  Purpose

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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Changes in mtDNA content [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • changes in mitochondrial function [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes in fat apoptosis [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • changes in oxidative damage biomarkers [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Estimated 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: 1
NucleomaxX 36 grams TID every other day
Drug: NucleomaxX
NucleomaxX 36 grams TID every other day
Active Comparator: Switch
Swicth of AZT or d4T to tenofovir
Drug: Tenofovir disoproxil fumarate
Swicth thymidine NRTI to tenofovir

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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 ClinicalTrials.gov identifier: NCT00119379

Locations
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Principal Investigator: Grace A. McComsey, MD Case Western Reserve University
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Grace McComsey, MD, Case Western Reserve University
ClinicalTrials.gov Identifier: NCT00119379     History of Changes
Other Study ID Numbers: 1R01AI060484-01A2B, 1R01-AI060484-01A2B
Study First Received: July 11, 2005
Last Updated: February 22, 2010
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
lipoatrophy
mitochondria
HIV
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lipodystrophy
Metabolic Diseases
Nutrition Disorders
Malnutrition
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 15, 2014