HIV patients treated with Highly Active AntiRetroviral Therapy (HAART) show significant metabolic symptoms, such as lipodystrophy, dyslipidemia, and insulin resistance. A possible contribution to these symptoms in HIV/HAART is a decrease in mitochondrial function, resulting in a decreased fatty acid oxidation. A combined regime of aerobic and resistance training has been demonstrated to increase lean body mass and reduce overall fat and truncal fat and the levels of triglyceride and LDL cholesterol.
Condition Intervention HIV Infection Hyperlipidemia Exercise
Dietary Supplement: l-carnitine
Genetics Home Reference related topics: Cholesterol
MedlinePlus related topics: AIDS Cholesterol Triglycerides
ChemIDplus related topics: Carnitine Cholesterol
U.S. FDA Resources
Study Type: Interventional Study Design: Treatment, Randomized, Double Blind (Subject, Investigator) , Placebo Control, Single Group Assignment, Efficacy Study
Official Title: Effects of Mixed Exercise Regime and L-Carnitine Supplementation on Kinetics of Triglyceride- Rich Lipoproteins in HIV Patients on HAART
Further study details as provided by University of California, Davis:
Primary Outcome Measures: Exercise and L-carnitine supplementation will reduce blood lactate levels, increase the VO2sub-max and the VLDL to leucine enrichment ratio in HIV/HAART patients, suggesting an overall improvement of muscle and hepatic mitochondrial function. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Estimated Enrollment: 24 Study Start Date: January 2008 Estimated Study Completion Date: December 2008
Arms Assigned Interventions A: Placebo Comparator Dietary Supplement: l-carnitine 3 gram daily dose
Detailed Description: The introduction of Highly Active AntiRetroviral Therapy (HAART) for AIDS and HIV has improved survival considerably. However, HIV patients treated with HAART show significant metabolic symptoms, such as lipodystrophy, dyslipidemia, and insulin resistance. A possible contribution to these dysmetabolic symptoms in HIV/HAART is a decrease in mitochondrial function, resulting in a decreased fatty acid oxidation. Life style modulation such as aerobic exercise and L-carnitine supplementation may be beneficial to mitochondrial function. Aerobic exercise improves the biogenesis and function of mitochondria. A combined regime of aerobic and resistance training has been demonstrated to increase lean body mass and reduce overall fat and truncal fat and the levels of triglyceride and LDL cholesterol. L-Carnitine plays an important role in the transfer of long-chain acyl groups into the mitochondrial matrix and potentially improves energy metabolism. Further, L-carnitine supplementation decreases serum triglyceride levels in HIV/HAART patients with hypertriglyceridemi a. However, little is known whether these life style modulations act synergistically in HIV/HAART patients.
We hypothesize that a mixed regimen of exercise (including both resistance and aerobic exercise) and L-carnitine supplementation will improve mitochondrial dysfunction in HIV/HAART patients, and therefore, alleviate dysmetabolic symptoms such as dyslipidemia and insulin resistance. In this randomized, placebo-controlled study, we will explore whether a mixed regimen of exercise, including both resistance and aerobic exercise, and L-carnitine supplementation affect lipids and remnant lipoproteins, adipokines, insulin resistance; blood lactate levels and VO2max; and kinetics of leucine and triglyceride- rich lipoproteins among African-American and Hispanic HIV-positive subjects undergoing HAART. Effects on muscle mitochondrial function will be assessed using exercise tests and body composition assessment (DEXA and Bioimpedance) , while effects on hepatic mitochondrial function will be assessed measuring the relation between leucine and VLDL-apoB metabolism. We believe that the proposed study will help to elucidate underlying mechanisms for metabolic complications and will offer new possibilities for intervention to reduce negative metabolic effects in HIV/HAART patients.
Ages Eligible for Study: 18 Years to 70 Years Genders Eligible for Study: Both
African American, Hispanic and Caucasian adults with HIV on a stable HAART regimen (either PI or NNRTI based) for at least the past 6 months between 18 to 70 years of age. Patients taking SSRI's (Selective Serotonin Reuptake Inhibitors), SNRI's (Serotonin/Norepine phrine Reuptake inhibitors) and Tetracyclic antidepressants will be included as the risk of seizure in these patients in combination with the L-Carnitine supplement would be rare. Patients on these medications should be on a stable dose for at least 4-6 months prior to enrollment in the study. Exclusion Criteria:
Diabetes Mellitus Cushing's syndrome Renal disease (i.e. CKD Stages 3-5) Unstable liver disease Untreated thyroid dysfunction Seizure disorder Patients with conditions that can lower seizure threshold (i.e. brain tumors) or are taking medication(s) known to lower seizure threshold Pregnant or nursing mothers BMI > 35 Ongoing hormone replacement therapy Hemoglobin levels less than 11 g/dl, and fasting triglyceride levels > 500 mg/dl. Subjects with ongoing hypolipidemic and warfarin therapy will be excluded. Additionally, patients taking Valproic Acid and / or Zidovudine will be excluded as these have been shown to deplete carnitine. Patients taking Venlafaxine and Bupropion will be excluded as these medications have a small risk (0.26% and 0.1-0.4% risk, respectively) of causing seizure in patients without a previous risk of seizure.
Contacts and Locations
Please refer to this study by its ClinicalTrials. gov identifier: NCT00572429
Contact: Alison Semrad, DO 916-703-9190 alison.semrad@ ucdmc.ucdavis. edu
Contact: Rayanne Hildreth, CCRP 916-703-9190 rayanne.hildreth@ ucdmc.ucdavis. edu
United States, California
CARES Active, not recruiting Sacramento, California, United States, 95814
Sponsors and Collaborators
University of California, Davis
California Research Center for the Biology of HIV in Minorities
Principal Investigator: Lars Berglund, MD, PhD UC Davis Health System
Responsible Party: University of California, Davis ( Lars Berglund, MD, Ph.D ) Study ID Numbers: 200715081 First Received: December 11, 2007 Last Updated: December 12, 2007 ClinicalTrials. gov Identifier: NCT00572429 Health Authority: United States: Institutional Review Board