Lipoic acid as an immune modulator in multiple sclerosis

硫辛酸作为多发性硬化症的免疫调节剂

• 批准号: 7019589
• 负责人: VIJAYSHREE YADAV
• 金额: $ 13.39万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7019589
• 关键词: antioxidants; biomarker; blood chemistry; cell adhesion molecules; clinical research; clinical trial phase I; enzyme linked immunosorbent assay; human subject; human therapy evaluation; immunologic assay /test; immunomodulators; interferon gamma; metalloendopeptidases; multiple sclerosis; nervous system disorder chemotherapy; patient oriented research; pharmacokinetics; questionnaires; relapse /recurrence; sign /symptom; tumor necrosis factor alpha

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.

描述（由申请人提供）：医学博士Vijayshree Yadav寻求资金为受过指导的患者研究职业发展奖，以获得设计和进行科学严格的临床试验所需的技能。 Yadav博士是董事会认证的神经科医生，已完成她的神经免疫学研究金。她的职业目标是成为一名独立的临床研究者。实现这些目标的计划包括获得临床研究硕士学位（MCR），并成功地进行了多发性硬化症（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博士将在MS中使用口服Lipoic Acid（LA）进行24周双盲盲型对照研究。 LA已被证明可以有效地治疗和抑制MS疾病模型小鼠中的实验性自身免疫性脑脊髓炎（EAE）。来自EAE研究的初步数据以及来自Yadav博士和她的导师Dennis Bourdette进行的MS患者的试点研究，对使用LA时提出了显着的免疫学影响。拟议的研究主要旨在评估MS患者24周LA给药的免疫学影响。该研究的主要目的是评估LA对MS中推定的生物标志物的影响，例如粘附分子和基质金属蛋白酶9以及其他炎症标记。次要结果将包括评估高剂量LA给药的安全性以及LA使用24周的潜在临床益处。该研究还将包括LA的药代动力学研究。六十位MS受试者的MS的复发形式将随机分为安慰剂或每天两次洛杉矶。该研究将在OHSU的一般临床研究中心进行。这项研究将有助于探索口服LA作为MS的潜在治疗方法。这项研究很重要，因为MS的当前治疗方案具有重大局限性，例如仅是部分有效的，仅以可注射形式可用，具有明显的副作用，并且非常昂贵。该申请为Yadav博士提出了一项结构化的教学培训计划，以确保她在5年奖励期末作为临床研究者的独立性。