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Sponsored by: |
National Center for Complementary and Alternative Medicine (NCCAM) |
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Information provided by: | National Center for Complementary and Alternative Medicine (NCCAM) |
ClinicalTrials.gov Identifier: | NCT00471614 |
The purpose of this study is to determine whether uridine supplementation will improve insulin sensitivity and overall carbohydrate metabolism in HIV-positive subjects who are currently undergoing treatment with antiretroviral regimens containing stavudine or zidovudine and who have evidence of impaired mitochondrial function and insulin resistance.
Condition | Intervention | Phase |
---|---|---|
HIV Infections Insulin Resistance Hyperlactatemia |
Drug: NucleomaxX (contains uridine) |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | Uridine Supplementation, Mitochondrial Function, and Glucose Metabolism in HIV |
Estimated Enrollment: | 20 |
Study Start Date: | April 2007 |
Estimated Study Completion Date: | December 2009 |
Estimated Primary Completion Date: | August 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
NucleomaxX
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Drug: NucleomaxX (contains uridine)
Escalated doses of NucleomaxX tid
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2: Placebo Comparator
Placebo
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Drug: NucleomaxX (contains uridine)
Escalated doses of NucleomaxX tid
|
Treatment of HIV infection with nucleoside analogue reverse transcriptase inhibitors (NRTIs) has been associated with numerous toxicities that have been attributed to impaired mitochondrial function secondary to a reduction in the levels of mitochondrial DNA (mtDNA). Abnormalities in mitochondrial function have been implicated in the development of insulin resistance in patients with HIV infection and have also been hypothesized to underlie many of the pathophysiologic features of type 2 diabetes mellitus in non-HIV infected individuals.
Uridine, a pyrimidine nucleoside that plays an essential role in the synthesis of RNA and other key physiologic processes, has been proposed as a therapy for NRTI-induced mitochondrial dysfunction. Uridine supplementation protected bone marrow cells from the toxicity of zidovudine, normalized the growth of neurons exposed to NRTIs, and abrogated mitochondrial toxicity of NRTIs in HepG2 cells in vitro. A food supplement called NucleomaxX®, extracted from the stem of sugar cane, raises plasma uridine concentrations to levels known to prevent mitochondrial toxicity in vitro. In a recent case report, oral administration of uridine, given in the form of NucleomaxX®, ameliorated the mitochondrial toxicity caused by stavudine and led to improvements in myalgias and liver and muscle enzymes, despite continuing treatment with stavudine. In a clinical study of 14 HIV-infected patients treated with stavudine or zidovudine, NucleomaxX® led to improved hepatic mitochondrial function as assessed by the 13C-methionine breath test.
We will perform a randomized double-blind placebo-controlled study in 20 HIV-positive subjects who are currently undergoing treatment with antiretroviral regimens containing stavudine or zidovudine and who have evidence of impaired mitochondrial function and insulin resistance. Subjects will be hospitalized in the SFGH CTSI Clinical Research Center (CCRC) for 6 days to undergo comprehensive metabolic studies. Subjects will then be randomized, in a 1:1 fashion, to receive either NucleomaxX® or placebo for two months, after which they will repeat the 6-day CCRC-based assessments. This study is designed to test the hypothesis that, in comparison to placebo, uridine supplementation will enhance mitochondrial function, and this will be associated with concomitant improvements in glucose and lipid metabolism.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Madhu N Rao, MD | 415-206-6381 | madhu.rao@ucsf.edu |
Contact: Kathleen Mulligan, PhD | 415-206-5882 | kathleen.mulligan@ucsf.edu |
United States, California | |
University of California San Francisco | Recruiting |
San Francisco, California, United States, 94110 |
Principal Investigator: | Morris Schambelan, MD | University of California, San Francisco |
Responsible Party: | University of California, San Francisco ( Morris Schambelan, MD ) |
Study ID Numbers: | R21 AT003374-01A1 |
Study First Received: | May 8, 2007 |
Last Updated: | August 22, 2008 |
ClinicalTrials.gov Identifier: | NCT00471614 |
Health Authority: | United States: Food and Drug Administration |
HIV AIDS uridine |
mitochondria insulin resistance Treatment Experienced |
Sexually Transmitted Diseases, Viral Stavudine Metabolic Diseases Acquired Immunodeficiency Syndrome Zidovudine Insulin Immunologic Deficiency Syndromes Virus Diseases |
Hyperinsulinism HIV Infections Sexually Transmitted Diseases Insulin Resistance Glucose Metabolism Disorders Metabolic disorder Retroviridae Infections |
RNA Virus Infections Slow Virus Diseases Immune System Diseases Lentivirus Infections Infection |