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| Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
|---|---|
| Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00119379 |
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 II |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study |
| Official Title: | Reversibility of Mitochondrial Toxicity in HIV Lipoatrophy |
| Estimated Enrollment: | 50 |
| Study Start Date: | April 2005 |
| Estimated Study Completion Date: | June 2010 |
| Estimated Primary Completion Date: | January 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1: Experimental
NucleomaxX 36 grams TID every other day
|
Drug: NucleomaxX
NucleomaxX 36 grams TID every other day
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Switch: Active Comparator
Swicth of AZT or d4T to tenofovir
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Drug: Tenofovir disoproxil fumarate
Swicth thymidine NRTI to tenofovir
|
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:
Exclusion Criteria:
Contacts and Locations| Contact: Grace A. McComsey, MD | 216-844-2460 | mccomsey.grace@clevelandactu.org |
| United States, Ohio | |
| University Hospitals of Cleveland | Recruiting |
| Cleveland, Ohio, United States, 44106 | |
| Contact: Grace A. McComsey, MD 216-844-2460 mccomsey.grace@clevelandactu.org | |
| Contact: Norma Storer, RN 216-844-2752 storer.norma@clevelandactu.org | |
| Principal Investigator: | Grace A. McComsey, MD | Case Western Reserve University |
More Information
| Responsible Party: | Case Western Reserve University ( Grace McComsey, MD ) |
| Study ID Numbers: | 1R01AI060484-01A2B, 1R01-AI060484-01A2B |
| Study First Received: | July 11, 2005 |
| Last Updated: | May 28, 2008 |
| ClinicalTrials.gov Identifier: | NCT00119379 History of Changes |
| Health Authority: | United States: Food and Drug Administration; United States: Federal Government |
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lipoatrophy mitochondria HIV treatment experienced |
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Anti-Infective Agents Sexually Transmitted Diseases, Viral Anti-HIV Agents Metabolic Diseases Skin Diseases Acquired Immunodeficiency Syndrome Antiviral Agents Immunologic Deficiency Syndromes Reverse Transcriptase Inhibitors Virus Diseases |
Anti-Retroviral Agents HIV Infections Lipodystrophy Sexually Transmitted Diseases Tenofovir Nutrition Disorders Retroviridae Infections Metabolic Disorder Tenofovir disoproxil Lipid Metabolism Disorders |
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Anti-Infective Agents Sexually Transmitted Diseases, Viral Slow Virus Diseases Molecular Mechanisms of Pharmacological Action Infection Reverse Transcriptase Inhibitors Anti-Retroviral Agents Therapeutic Uses Lipodystrophy Nutrition Disorders Tenofovir Retroviridae Infections Nucleic Acid Synthesis Inhibitors Tenofovir disoproxil RNA Virus Infections |
Anti-HIV Agents Metabolic Diseases Immune System Diseases Skin Diseases Acquired Immunodeficiency Syndrome Enzyme Inhibitors Antiviral Agents Immunologic Deficiency Syndromes Pharmacologic Actions Virus Diseases HIV Infections Skin Diseases, Metabolic Sexually Transmitted Diseases Lentivirus Infections Lipid Metabolism Disorders |
