Complementary treatment approach to epilepsy

描述(由申请者提供)：候选人西格沃德·埃尔萨斯博士寻求资助一项以患者为导向的指导研究职业发展奖，以获得癫痫CAM领域的独立临床研究人员的技能。在为期五年的培训期间，埃尔萨斯博士将进行一项植物疗法治疗癫痫的临床试验。 临床试验将评估一种植物疗法治疗癫痫的安全性和有效性。广受欢迎的植物西番莲花是癫痫患者常用的。已发现西番莲花黄酮类化合物可以预防戊四氮诱发的癫痫发作，并在动物模型中激活抑制性GABA电流。 目的1：验证西番莲是一种有效的植物疗法治疗癫痫的假说。西番莲提取物将在俄勒冈健康与科学大学(OHSU)的生药学实验室进行类黄酮含量分析，然后将通过NIH抗惊厥筛选计划在一系列动物模型中重新测试其抗惊厥活性的剂量范围。黄酮类标准化的PASS/FLORA INCANTATA提取物将在一项随机安慰剂对照的II期临床试验中测试它们在减少部分癫痫患者癫痫发作频率方面的有效性。我们还将在使用标准化焦虑量表的随机安慰剂对照临床试验中测试类黄酮类标准化西番莲提取物是否有效降低癫痫患者的焦虑。 目的2：验证西番莲是一种安全的植物疗法治疗癫痫的假设。西番莲提取物的安全剂量和可能的直接副作用将在小型I期临床试验和II期试验中通过心电、血液学和肝功能测试进行测试。在第二阶段临床试验中，西番莲提取物与抗惊厥新陈代谢的可能相互作用将通过密切跟踪患者的抗惊厥药物水平来检验。西番莲提取物对镇静、抗惊厥副作用的可能增强作用将在第二阶段临床试验中通过认知测试和问卷调查来检验。在获奖期间，Elsas博士将继续接受OHSU人类调查项目临床调查硕士学位的培训。他将学习进行临床试验和应用生物统计学。Elsas博士将了解CAM的一般知识、生药学和植物学的监管环境，包括IND的申请程序。在所有方面的培训中，埃尔萨斯博士将由他的导师巴里·奥肯(Barry Oken)指导，巴里·奥肯是俄勒冈州立大学神经疾病补充和替代医学中心的主任。在获奖期结束时，埃尔萨斯博士将完成一项植物学的临床试验，并将处于获得独立研究资金的有利地位。

DESCRIPTION (provided by applicant): The candidate, Dr. Siegward Elsas, seeks funding for a Mentored Patient-Oriented Research Career Development Award to obtain the skills as an independent clinical researcher in the area of CAM in epilepsy. During the five-year training period, Dr. Elsas will conduct a clinical trial of a botanical treatment for epilepsy. The clinical trial will evaluate the safety and efficacy of a botanical treatment of epilepsy. The popular botanical Passionflower is commonly used by epilepsy patients. Passionflower flavonoids have been found to prevent pentylenetetrazol-induced seizures and to activate inhibitory GABA currents in animal models. Aim 1: Test the hypothesis that Passiflora is an effective botanical treatment for epilepsy. Passiflora incarnata extracts will be analyzed for flavonoid content at the pharmacognosy laboratory at Oregon Health and Science University (OHSU), and will then be retested for their dosage range of anticonvulsant activity in a series of animal models by the NIH anticonvulsant screening program. Flavonoid-standardized Pass/flora incarnata extracts will be tested for their effectiveness in reducing seizure frequency in partial epilepsy patients in a randomized placebo-controlled phase II clinical trial. We will also test if flavonoid-standardized Passiflora incarnata extracts are effective in reducing anxiety in epilepsy patients in the randomized placebo-controlled clinical trial using standardized anxiety scales. Aim 2: Test the hypothesis that Passiflora is a safe botanical treatment of epilepsy. Safe dosing and possible direct side effects of Passiflora extracts will be tested by ECG, hematological and liver function testing in a small phase I clinical trial and again in the phase II trial. Possible interactions of Passiflora extracts with anticonvulsant metabolism will be examined by closely following patient anticonvulsant levels in the phase II clinical trial. Possible potentiation of sedative anticonvulsant side effects by Passiflora extracts will be examined by cognitive testing and questionnaires in the phase II clinical trial. During the period of the award, Dr. Elsas will pursue training towards a Master's degree in clinical investigation in the Human Investigations Program at OHSU. He will learn to conduct clinical trials and to apply biostatistics. Dr. Elsas will learn about CAM in general, about pharmacognosy, and about the regulatory environment for botanicals including the application process for an IND. In all aspects of his training, Dr. Elsas will be supervised by his mentor Barry Oken, director of the Oregon Center for Complementary and Alternative Medicine in Neurological Disorders at OHSU. At the end of the award period, Dr. Elsas will have completed a clinical trial of a botanical and will be well positioned to obtain independent research funding.