Painful HIV Neuropathy: Treatment with Alpha-Lipoic Acid

描述（由申请人提供）：HIV感染与高达35 - 50%的非艾滋病患者和70%以上的晚期疾病患者的疼痛性远端周围多发性神经病相关。疼痛位于四肢远端，是对称的、自发的、中度至重度的，并伴有不同程度的虚弱和感觉丧失。疼痛被描述为烧灼感、压迫感和休克样，具有持续和间歇性特征。这种情况是渐进的，但可能会停止与疾病缓解。残疾往往是重大的，从疼痛的波动强度和疼痛本身的性质。外周神经轴突和感觉，背根神经节中的神经元细胞体是导致症状的过程的主要目标。传统的药物治疗包括抗惊厥药、三环类抗抑郁药、阿片类药物和辅助药物，所有这些药物都有明显的副作用和有限的疗效。 α-硫辛酸是一种八碳二硫化物，天然存在于身体的所有细胞中，它是导致能量产生的关键线粒体酶促反应的关键辅因子。在高浓度下，它直接作为抗氧化剂，再生其他抗氧化剂，如谷胱甘肽和维生素C和E，并促进谷胱甘肽的合成。使用α-硫辛酸治疗疼痛性糖尿病神经病变的临床研究表明，每日口服剂量耐受良好具有显著益处：糖尿病神经病变与疼痛性HIV神经病变具有共同的临床和某些病理特征。 本研究旨在评价每日口服α-硫辛酸补充剂加标准医疗护理在治疗18岁及以上受试者疼痛性HIV相关神经病变6个月期间的效果。对照组将接受标准医疗护理加安慰剂六个月。主要终点包括疼痛、止痛药的使用和外周神经功能。将在基线和研究终止时获得当前情绪、抑郁和沿着生活质量的测量值以及HIV疾病活动和线粒体功能的血清标志物，以与临床结局相关。这项研究对HIV相关疼痛性神经病患者的可能益处包括减少疼痛和残疾，减少药物使用和增强细胞代谢。

DESCRIPTION (provided by applicant): HIV infection is associated with painful distal peripheral polyneuropathy in up to 35 to 50% of those without AIDS and in more than 70% of those with advanced disease. Pain is located distally in the extremities, is symmetrical, spontaneous, moderate to severe and associated with varying degrees of weakness and sensory loss. The pain is described as burning, pressure and shock-like with both constant and intermittent features. The condition is progressive but may be halted with disease remission. Disability is often significant, arising from the fluctuating intensity of the pain and the character of the pain itself. Peripheral nerve axons and sensory, neuron cell bodies in the dorsal root ganglia are the principal targets of the process leading to symptoms. Conventional medical treatment consists of anticonvulsants, tricyclic antidepressants, opiates and adjuvant medications, all of which have significant side effects and limited effectiveness. Alpha-lipoic acid is an eight carbon disulfide, naturally occurring in all cells of the body, which serves as a critical cofactor for key mitochondrial enzymatic reactions leading to energy production. In high concentrations it acts as an antioxidant directly, regenerates other anti-oxidants such as glutathione and vitamins C and E, and promotes glutathione synthesis. Clinical studies in using alpha-lipoic acid for painful diabetic neuropathy have shown significant benefit at daily oral doses that are well tolerated: Diabetic neuropathy shares both clinical and some pathological features with painful HIV neuropathy. The present study is designed to evaluate the effects of using daily oral supplements of alpha-lipoic acid plus standard medical care in the treatment of painful HIV-associated neuropathy over a 6 month period in subjects 18 and older. A control group will receive standard medical care plus placebo for six months. Primary endpoints include pain, use of pain medication and peripheral nerve function. Measures of current mood, depression and quality of life along with serum markers of HIV disease activity and mitochondrial function will be obtained at baseline and study termination for correlation with clinical outcomes. Possible benefits of the study to patients with HIV-associated painful neuropathy include reduction in pain and disability, reduced use of medications and enhanced cellular metabolism.