CLINICAL TRIAL: THE EFFECT OF DICHLOROACETATE ON AEROBIC FUNCTION AND WORK CAPAC

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our objective is to examine the effects of the drug dichloroacetate-DCA on aerobic function and maximal work capacity in patients with congenital lactic acidosis-CLA. We will recruit 10 individuals with documented disease to comprise our patient cohort. We will enroll a cohort of healthy volunteers to serve as a normal comparison group. In experiment 1, Patients with CLA will perform a graded exercise test to voluntary maximal exertion on a cycle ergometer while treated with either DCA or placebo. We hypothesize that DCA treatment will increase the VO2 at the individual lactate threshold-LT, VO2max, and maximal work capacity in patients with CLA. In experiment 2, using the data from experiment 1, patients with CLA will perform a 15-minute exercise bout at an intensity designed to elicit 80% of the VO2 at LT. We hypothesize that patients with CLA who are treated with DCA, compared with placebo, will demonstrate reduced levels of lactic acid, increased rates of carbohydrate oxidation, increased cardiac and ventilatory efficiency, and decreased ratings of perceived exertion-RPE during a submaximal exercise bout prescribed at a level related to their individual LT. We will compare both exercise responses to a cohort of healthy volunteers, not treated with either DCA or placebo. We hypothesize that patients with CLA will have reduced levels of aerobic function, compared to the control group. DCA treatment in patients with CLA will attenuate these differences. We hope to demonstrate that DCA can improve aerobic function in patients with CLA.