Complementary treatment approach to epilepsy

描述（由申请人提供）：候选人Siegward Elsas博士寻求资助以指导患者为导向的研究职业发展奖，以获得癫痫CAM领域独立临床研究人员的技能。在为期五年的培训期间，Elsas博士将进行一项植物治疗癫痫的临床试验。 这项临床试验将评估植物治疗癫痫的安全性和有效性。流行的植物西番莲是癫痫患者常用的。西番莲黄酮类化合物已被发现可以防止戊四氮诱导的癫痫发作，并激活抑制性GABA电流的动物模型。 目的1：验证西番莲是一种有效的癫痫植物治疗的假设。将在俄勒冈州健康与科学大学（OHSU）的生药学实验室分析粉色西番莲提取物的类黄酮含量，然后通过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。将在一项随机安慰剂对照II期临床试验中测试类黄酮标准化的Pass/植物群胭脂树提取物在降低部分性癫痫患者癫痫发作频率方面的有效性。我们还将使用标准化焦虑量表在随机安慰剂对照临床试验中测试类黄酮标准化的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癫痫植物治疗的假设。西番莲提取物的安全剂量和可能的直接副作用将在一项小型I期临床试验中通过ECG、血液学和肝功能测试进行测试，并再次在II期试验中进行测试。将通过密切跟踪II期临床试验中患者的抗惊厥药物水平，检查西番莲提取物与抗惊厥药物代谢的可能相互作用。在II期临床试验中，将通过认知测试和问卷调查来检查西番莲提取物对镇静抗惊厥副作用的可能增强作用。在获奖期间，Elsas博士将在OHSU的人类调查项目中攻读临床调查硕士学位。他将学习进行临床试验和应用生物统计学。Elsas博士将学习CAM的一般知识，生药学知识，以及植物药的监管环境，包括IND的申请过程。在他培训的各个方面，Elsas博士将由他的导师巴里奥肯（OHSU俄勒冈州神经疾病补充和替代医学中心主任）监督。在奖励期结束时，Elsas博士将完成一项植物药的临床试验，并将有能力获得独立的研究资金。

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.