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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们的目的是观察药物二氯乙酸二乙酯对先天性乳酸酸中毒患者有氧功能和最大工作能力的影响。我们将招募10名有记录的疾病患者组成我们的患者队列。我们将招募一组健康志愿者作为正常对照组。在实验1中，CLA患者将在服用DCA或安慰剂的同时，在自行车功率计上进行自愿最大负荷的分级运动试验。我们假设DCA治疗将增加CLA患者个体乳酸阈值下的VO2-LT、VO2max和最大工作能力。在实验2中，使用实验1的数据，CLA患者将进行15分钟的运动，强度设计为在LT时引起80%的VO2。我们假设，与安慰剂相比，接受DCA治疗的CLA患者将显示出乳酸水平降低，碳水化合物氧化速率增加，心脏和呼吸效率增加，感觉到的劳累-RPE评分降低。我们将把这两种运动反应与一组健康志愿者进行比较，这些志愿者既没有服用DCA，也没有服用安慰剂。我们假设，与对照组相比，CLA患者的有氧功能水平将会降低。对CLA患者进行DCA治疗将减弱这些差异。我们希望证明DCA可以改善CLA患者的有氧功能。

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.