Lipoic acid as an immune modulator in multiple sclerosis

描述(由申请人提供)：Vijayshree Yadav，医学博士寻求资助一个以患者为导向的指导研究职业发展奖，以获得设计和进行科学严格的临床试验所需的技能。亚达夫博士是一名获得委员会认证的神经科医生，她已经完成了神经免疫学方面的研究。她的职业目标是成为一名独立的临床研究员。实现这些目标的计划包括获得临床研究(MCR)硕士学位，并成功地进行多发性硬化症(MS)的I期临床试验。MCR课程是OHSU人类调查计划(HIP)的一部分，由NIH赞助。Yadav博士将在MS中使用口服硫辛酸(LA)进行为期24周的双盲安慰剂对照研究，LA已被证明在治疗和抑制实验性自身免疫性脑脊髓炎(EAE)方面有效，EAE是MS的疾病模型。来自EAE研究以及由Yadav博士和她的导师Dennis Bourderte博士对MS患者进行的试点研究的初步数据表明，使用LA具有显著的免疫学效果。这项拟议的研究主要是为了评估多发性硬化症患者服用24周LA的免疫学效果。这项研究的主要目标将是评估LA对多发性硬化症可能的生物标志物的影响，如黏附分子和基质金属蛋白酶-9以及其他炎症标志物。次要结果将包括对大剂量LA给药的安全性和24周LA给药的潜在临床益处的评估。该研究还将包括LA的药代动力学研究。60名患有复发缓解型多发性硬化症的患者将随机接受安慰剂或1200毫克的LA治疗，每天两次。这项研究将在OHSU的综合临床研究中心进行。这项研究将有助于探索口服LA作为治疗多发性硬化症的潜在方法。这项研究是相关的，因为目前治疗多发性硬化症的选择有很大的局限性，如只有部分有效，仅有注射形式可用，具有显著的副作用和非常昂贵的费用。本申请为Yadav博士提出了一项有系统的教学培训计划，以确保她在5年获奖期结束时作为临床研究人员的独立性。

DESCRIPTION (provided by applicant): Vijayshree Yadav, MD seeks funding for a Mentored Patient Oriented Research Career Development Award to obtain the skills necessary to design and conduct scientifically rigorous clinical trials. Dr Yadav is a board certified neurologist who has completed her fellowship in Neuroimmunology. Her career goal is to become an independent clinical investigator. The plans for achieving these objectives include obtaining a master's degree in clinical research (MCR) and successfully conducting a phase I clinical trial in multiple sclerosis (MS). The MCR course is offered as part of Human Investigations Program (HIP) at OHSU that is sponsored by NIH. Dr Yadav will conduct a 24-week double blind placebo controlled study using oral lipoic Acid (LA) in MS. LA has been shown to be effective in treating and suppressing experimental autoimmune encephalomyelitis (EAE) in mice, a disease model for MS. There is preliminary data from the EAE studies as well as from a pilot study in MS patients done by Dr Yadav and her mentor Dr Dennis Bourdette suggesting significant immunological effects upon use of LA. The proposed study is designed primarily to assess the immunological effects of 24-week of administration of LA in MS patients. The primary goal of the study will be to assess effects of LA on putative biomarkers in MS such as adhesion molecules and matrix metalloproteinase-9 along with other inflammatory markers. The secondary outcomes will include assessment of safety of high dose LA administration and potential clinical benefits from 24 weeks of LA use. The study will also include pharmacokinetic study of LA. Sixty MS subjects with relapsing remitting form of MS will be randomized to placebo or 1200 mg twice a day of LA. The study will be conducted at the General Clinical Research Center at the OHSU. This study will help in exploring oral LA as potential treatment for MS. The study is relevant as the present treatment options for MS have significant limitations such as being only partially effective, available only in injectable forms, with significant side effects and very costly. This application proposes a structured didactic training program for Dr Yadav to ensure her independence as a clinical investigator at the end of the 5 year award period.