Effectiveness of Nucleoside Supplementation and Substituting Tenofovir Disoproxil Fumarate for Other Drugs in Anti-HIV Regimens in Reversing Fat Loss in HIV Infected Adults
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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 |
- 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 ]
- 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 |
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 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 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 March 07, 2013
