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: 7490648
• 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/7490648
• 关键词: Adverse effects; Animal Model; Antioxidants; Award; Biological Markers; Caring; Cell Adhesion Molecules; Central Nervous System Diseases; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Clinical effectiveness; Data; Demyelinations; Development; Diabetic Polyneuropathies; Disease; Disease model; Dose; Double-Blind Method; Drug Kinetics; Encephalomyelitis; Ensure; Experimental Autoimmune Encephalomyelitis; Fellowship; Funding; Future; Gelatinase B; Goals; Human; Immune; Inflammation; Inflammation Mediators; Inflammatory; Injectable; Injury; Intercellular adhesion molecule 1; Interferons; Investigation; Knowledge; Lesion; Long-Term Effects; Master' s Degree; Mediator of activation protein; Mentored Patient-Oriented Research Career Development Award; Mentors; Multiple Sclerosis; Mus; Neuraxis; Neurologist; Oral; Outcome; Pathology; Patients; Personal Satisfaction; Phase I Clinical Trials; Phase II Clinical Trials; Pilot Projects; Placebo Control; Placebos; Production; Randomized; Rate; Recombinant Interferon Beta; Relapse; Research; Research Personnel; Safety; Serum; Structure; Symptoms; T-Lymphocyte; Testing; Therapeutic; Thioctic Acid; Training Programs; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States National Institutes of Health; Week; Work; base; career; cell motility; clinical efficacy; copolymer 1; cytokine; day; design; dietary supplements; experience; human TNF protein; improved; innovation; macrophage; migration; natalizumab; neuroimmunology; novel strategies; pilot trial; placebo controlled study; pre-clinical; preclinical study; programs; skills

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）：Vijayshree Yadav 医学博士寻求资助以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 博士是一名经过委员会认证的神经科医生，已完成神经免疫学专科培训。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 (MCR) 硕士学位并成功开展多发性硬化症 (MS) 的 I 期临床试验。 MCR 课程是 OHSU 人类研究计划 (HIP) 的一部分，由 NIH 赞助。 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) 治疗多发性硬化症。 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)（一种多发性硬化症疾病模型）。 EAE 研究以及 Yadav 博士和她的导师 Dennis Bourdette 博士对 MS 患者进行的一项试点研究提供了初步数据，表明使用 LA 会产生显着的免疫学影响。拟议的研究主要旨在评估 MS 患者服用 LA 24 周后的免疫学效果。该研究的主要目标是评估 LA 对多发性硬化症中假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 以及其他炎症标志物。次要结果将包括评估高剂量 LA 给药的安全性以及使用 24 周 LA 的潜在临床益处。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 MS 的 MS 受试者将被随机分配到安慰剂组或每天两次 1200 毫克的 LA 组。该研究将在 OHSU 的普通临床研究中心进行。这项研究将有助于探索口服 LA 作为多发性硬化症的潜在治疗方法。这项研究具有重要意义，因为目前的多发性硬化症治疗方案具有显着的局限性，例如仅部分有效、仅以注射剂形式提供、具有显着的副作用且成本高昂。该申请为 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。