Lipoic acid as an immune modulator in multiple sclerosis

描述（由申请人提供）：医学博士Vijayshree Yadav寻求资助一个指导患者为导向的研究职业发展奖，以获得设计和进行科学严谨的临床试验所需的技能。Yadav博士是一名获得委员会认证的神经学家，她已经完成了神经免疫学的研究。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，并成功进行多发性硬化症（MS）的I期临床试验。MCR课程是由NIH赞助的OHSU人类调查计划（HIP）的一部分。Yadav博士将进行一项为期24周的双盲安慰剂对照研究，使用口服硫辛酸（LA）治疗MS。LA已被证明可有效治疗和抑制小鼠实验性自身免疫性脑脊髓炎（EAE），来自EAE研究以及Yadav博士和她的导师Dennis Bourdette博士在MS患者中进行的试点研究的初步数据表明，对使用LA的影响拟定的研究主要旨在评估MS患者给予LA 24周的免疫学效应。本研究的主要目的是评估LA对MS中假定生物标志物的影响，如粘附分子和基质金属蛋白酶沿着其他炎症标志物。次要结局将包括评估高剂量LA给药的安全性和LA使用24周的潜在临床获益。本研究还将包括LA的药代动力学研究。将60例复发缓解型MS受试者随机分配至安慰剂组或1200 mg每日两次LA组。本研究将在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MS的潜在治疗方法。这项研究是相关的，因为目前MS的治疗选择具有显著的局限性，例如仅部分有效，仅以注射形式提供，具有显著的副作用并且非常昂贵。本申请为Yadav博士提出了一个结构化的教学培训计划，以确保她在5年奖励期结束时作为临床研究者的独立性。

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.