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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的目的是研究药物二氯醋酸盐对CLA患者有氧功能和最大作功能力的影响。 我们将招募10名有疾病记录的患者组成我们的患者队列。 我们将招募年龄和性别匹配的健康志愿者队列作为正常对照组。 本研究将采用两种实验条件来测试特定的假设。 我们将研究DCA对CLA患者在踏车运动中乳酸动力学、最大摄氧量（VO2 max）和最大作功能力的影响。患者在接受DCA或安慰剂治疗时，将在自行车测力计上进行分级运动试验，以达到自愿最大用力。 我们假设DCA治疗将显著增加CLA患者个体乳酸阈值时的VO2。 在实验2中，我们将研究DCA治疗对CLA患者乳酸产生、底物利用和次极量运动的血流动力学反应的影响。患者将进行一次15分钟的运动，强度设计为在LT时引起80%的VO2。我们假设CLA患者将表现出乳酸水平降低，碳水化合物氧化速率增加，心脏和呼吸效率增加，以及感知运动评分降低;最后，我们将比较这两种实验条件下的运动反应与一组健康志愿者，调整年龄和性别，未接受DCA或安慰剂治疗。

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 on aerobic function and maximal work capacity in patients with CLA. We will recruit 10 individuals with documented disease to comprise our patient cohort. We will enroll age and gender matched cohort of healthy volunteers as normal comparison group. This investigation will employ two experimental conditions to test specific hypotheses. We will examine the effect of DCA on lactate kinetics, maximal oxygen uptake (VO2 max) and maximal work capacity during graded exercise on a cycle ergometer in patients with CLA. Patients 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 significantly increase the VO2 at the individual lactate threshold in patients with CLA. In experiment 2, we will examine the effect of DCA treatment on lactate production, substrate utilization, and hemodynamic responses to submaximal exercise in patients with CLA. Patients will perform a 15-minute exercise bout at an intensity designed to elicit 80% of the VO2 at LT. We hypothesize patients with CLA will demonstrate reduced levels of lactic acid, increased rates of carbohydrate oxidation, increased cardiac and ventilatory efficiency, and decreased ratings of perceived exertion; during a submaximal exercise bout prescribed at a level related to their individual LT. Finally, we will compare the exercise responses under these two experimental conditions to a cohort of healthy volunteers, adjusting for age and sex, not treated with either DCA or placebo.