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New study: Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy
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This study is not yet open for patient recruitment.
Verified by National Institute of Allergy and Infectious Diseases (NIAID) March 2006 Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Purpose Lipoatrophy, the loss of body fat from particular areas of the body, is a common side effect of antiretroviral therapy (ART). The purpose of this study is to determine the effectiveness of uridine supplementation in treating HIV infected individuals on stable ART with lipoatrophy.
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Trial of Uridine Supplementation in HIV Lipoatrophy
Primary Outcomes: Change in bone densitometry (DEXA)-measured limb fat from baseline to Week 48
Secondary Outcomes: Signs and symptoms, laboratory-based toxicity, and discontinuation rates of the regimens; change in DEXA-measured limb fat from baseline to Week 24; change in HIV RNA and CD4 count from baseline through Week 48; change in level of venous lactate from baseline through Week 48; change in level of fasting lipids from baseline through Week 48; change in level of plasma F2 isoprostanes, PBMC MDA and common deletion mitochondrial DNA from baseline through Week 48; change in level of fasting glucose and insulin from baseline through Week 48; change in PBMC mitochondrial DNA from baseline through Week 48; change in PBMC endogenous nucleoside pools from baseline through Week 48; change in hemoglobin, leukocytes, and creatine kinase from baseline through Week 48
Expected Total Enrollment: 164
Lipoatrophy is a distressing long-term complication of ART and is associated with decreased quality of life, an increased risk of cardiovascular disease, and nonadherence to ART. The cause of lipoatrophy in HIV infected individuals receiving ART is not completely understood; however, research suggests that mitochondrial toxicity in subcutaneous adipose tissue caused by thymidine analogue nucleoside analogues may be responsible for the development of lipoatrophy.
Uridine is a nucleoside that has been shown to be an effective supplement in treating individuals with mitochondrial toxicity. NucleomaxX is a food supplement that consists of mitocnol, a sugar cane extract that
has a high content of nucleosides, including uridine. The purpose of this study is to evaluate the effects of uridine supplementation in the form of NucleomaxX on limb fat in HIV infected individuals receiving stable ART containing stavudine (d4T) or zidovudine (ZDV). In addition, this study will evaluate the safety and tolerability of NucleomaxX.
This study will last 48 weeks. Participants will be randomly assigned to 1 of 2 arms. Arm A participants will receive NucleomaxX, while Arm B participants will receive a placebo. Participants in both arms will receive their assigned intervention three times per day, every other day, for the duration of the study. There will be 8 study visits over the 48-week study. Blood collection and a physical exam will occur at all study visits; participants will complete an adherence assessment at most visits. Specific fasting tests for glucose and lipid levels will occur at selected visits. ART will not be provided by this study.
Eligibility Ages Eligible for Study: 18 Years and above, Genders Eligible for Study: Both
Criteria
Inclusion Criteria:
- HIV-1 infected
- Stable ART containing zidovudine or stavudine for at least 12 consecutive weeks prior to study entry
- Cumulative ART with zidovudine or stavudine for at least 24 weeks prior to study entry
- Viral load of 5,000 copies/ml or less within 45 days prior to study entry
- Lipoatrophy in at least two of the following areas: face, arms, legs, OR buttocks
- Not planning to add to or change current vitamin supplementation
- Willing to use acceptable forms of contraception
Exclusion Criteria:
- Life expectancy of less than 12 months
- Currently enrolled in or planning to enroll in an ART interruption study
- Plans to change current ART regimen
- Liver failure at anytime prior to study entry
- Greater than Grade 2 diarrhea or vomiting within 7 days prior to study entry
- Current AIDS-defining opportunistic infection or illness. Individuals with cutaneous Kaposi's sarcoma not requiring chemotherapy are not excluded.
- Currently receiving insulin or oral hypoglycemic products for diabetes mellitus
- Systemic cancer chemotherapy or immunomodulating agents within 30 days prior to study entry
- Systemic steroids for a cumulative duration of longer than 4 weeks within the 6 months prior to study entry
- Known allergy or sensitivity to study drug or any of its components
- Severe lactose intolerance
- Current drug or alcohol abuse or dependence
- Clinically significant illness requiring systemic treatment or hospitalization
- Chronic disability or serious illness that may affect body composition
- Received an investigational drug other than NucleomaxX or uridine for lipoatrophy within 30 days prior to study entry
- Certain abnormal laboratory values
- Pregnancy or breastfeeding
Location and Contact Information Please refer to this study by ClinicalTrials.gov identifier NCT00307164
Study chairs or principal investigators
Grace A. McComsey, MD, Study Chair, Division of Infectious Diseases, Case Western Reserve University
Judith A. Aberg, MD, Study Chair, New York University School of Medicine
More Information
Click here for more information on lipodystrophy
Click here for more information on lactic acidosis/hepatic steaosis
Publications
Koch EC, Schneider J, Weis R, Penning B, Walker UA. Uridine excess does not interfere with the antiretroviral efficacy of nucleoside analogue reverse transcriptase inhibitors. Antivir Ther. 2003 Oct;8(5):485-7. No abstract available.
McComsey GA, Walker UA. Role of mitochondria in HIV lipoatrophy: insight into pathogenesis and potential therapies. Mitochondrion. 2004 Jul;4(2-3):111-8.
Nolan D, Hammond E, Martin A, Taylor L, Herrmann S, McKinnon E, Metcalf C, Latham B, Mallal S. Mitochondrial DNA depletion and morphologic changes in adipocytes associated with nucleoside reverse transcriptase inhibitor therapy. AIDS. 2003 Jun 13;17(9):1329-38.
Walker UA, Venhoff N. Uridine in the prevention and treatment of NRTI-related mitochondrial toxicity. Antivir Ther. 2005;10 Suppl 2:M117-23. Review.
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