Clinical Trial: Effects of Uridine Supplementation on Metabolic Side Effects of Stavudine and Zidovudine

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Uridine Supplementation, Mitochondrial Function, and Glucose Metabolism in HIV

Brief Summary: 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.

Detailed Summary:

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 insu
Sponsor: National Center for Complementary and Integrative Health (NCCIH)

Current Primary Outcome: Change in insulin sensitivity as measured by euglycemic hyperinsulinemic clamp (with simultaneous stable isotope tracer studies) [ Time Frame: 2 months ]

Original Primary Outcome: Change in insulin sensitivity as measured by euglycemic hyperinsulinemic clamp (with simultaneous stable isotope tracer studies)

Current Secondary Outcome:

  • Change in body composition (DEXA and CT imaging) [ Time Frame: 2 months ]
  • Change in insulin secretion (frequently sampled intravenous glucose tolerance test) [ Time Frame: 2 months ]
  • Change in resting energy expenditure (indirect calorimetry) [ Time Frame: 2 months ]
  • Change in markers of oxidative stress [ Time Frame: 2 months ]
  • Change in mtDNA levels (measured in muscle biopsy) [ Time Frame: 2 months ]
  • Change in HIV disease markers [ Time Frame: 2 months ]
  • Adverse effects [ Time Frame: continuously ]
  • Laboratory based toxicity [ Time Frame: continuously ]
  • Adherence [ Time Frame: continuously ]


Original Secondary Outcome:

  • Change in body composition (DEXA and CT imaging)
  • Change in insulin secretion (frequently sampled intravenous glucose tolerance test)
  • Change in resting energy expenditure (indirect calorimetry)
  • Change in markers of oxidative stress
  • Change in mtDNA levels (measured in muscle biopsy)
  • Change in HIV disease markers
  • Adverse effects
  • Laboratory based toxicity
  • Adherence


Information By: National Center for Complementary and Integrative Health (NCCIH)

Dates:
Date Received: May 8, 2007
Date Started: April 2007
Date Completion:
Last Updated: May 15, 2012
Last Verified: May 2012