Huperzine for Cognitive and Functional Impairment in Schizophrenia

描述(申请人提供)：精神分裂症在美国影响着大约300万人，是导致残疾的主要原因之一。目前可用的药物只有部分有效，特别是对导致功能丧失的认知障碍。在中国进行的有限临床试验中，一种新药BMD-101已被证明在实验动物中具有神经保护、神经营养、胆碱能和多巴胺能作用，并似乎有利于认知症状。这项研究将测试BMD-101与现有药物一起使用时是否比现在更有效地治疗精神分裂症的认知和功能障碍。这种方法的优点和可行性将在两年内通过对72名对当前治疗没有最佳反应的精神分裂症患者进行随机、双盲、安慰剂对照、为期6个月的附加试验，比较两种剂量的BMD-101和安慰剂来确定。根据NIMH和FDA开发的Matrics电池的评估，这项初步研究的主要结果将是认知能力的改善。将评估一项共同的主要功能结果衡量标准，以满足FDA关于治疗精神分裂症认知功能障碍的适应症的要求。此外，安全性将通过不良事件报告、体检、生命体征、体重、心电图以及肝、肾、血液和代谢功能的实验室测试进行评估。有关疗效大小和安全性的数据将指导最终疗效研究的设计。第一年的里程碑将是试验中48名患者的随机化，完成第13周后续Matrics评估的75%的受试者保留13周，完成第26周后续Matrics评估的保留26周的66%。第二年的里程碑将是试验中72名患者的随机化，完成第13周后续Matrics评估的75%的受试者保留13周，完成第26周后续Matrics评估的保留26周的66%。在美国，精神分裂症影响着大约300万人，是导致残疾的主要原因之一。与公共卫生相关：目前可用的精神分裂症治疗只有部分有效，特别是对与疾病相关的功能缺陷背后的认知障碍。这项研究的重点是开发一种具有增强认知和神经保护特性的新药，当与现有药物一起使用时，可能会更有效地治疗精神分裂症的认知和功能障碍。

DESCRIPTION (provided by applicant): Schizophrenia affects approximately 3 million people in the US, and it is one of the leading causes of disability. Currently available drugs are only partially effective, particularly for the cognitive impairments that contribute to functional loss. A new investigational drug, BMD-101, has been shown to have neuroprotective, neurotrophic, cholinergic, and dopaminergic effects in laboratory animals and appeared to benefit cognitive symptoms in limited clinical trials conducted in China. This research will test whether BMD-101 when used together with existing drugs may more effectively treat the cognitive and functional impairments of schizophrenia than is now possible. The merit and feasibility of this approach will be established over two years by conducting a randomized, double-blind, placebo-controlled, 6-month add-on trial comparing two doses of BMD-101 to placebo in 72 patients with schizophrenia who have not responded optimally to current therapy. The primary outcome for this pilot study will be cognitive improvements as assessed by the NIMH- and FDA-developed MATRICS battery. A co-primary functional outcome measure will be evaluated to meet FDA requirements for the indication of treating cognitive dysfunction in schizophrenia. Additionally, safety will be assessed by adverse event report, physical exam, vital signs, weight, EKG, and laboratory tests of hepatic, renal, hematologic, and metabolic function. Data on effect sizes and safety will guide design of definitive efficacy studies. The milestones for year one will be randomization of 48 patients in the trial, retention for 13 weeks of 75% of subjects with completion of the week 13 follow-up MATRICS assessment, and retention for 26 weeks of 66% with completion of the week 26 follow- up MATRICS assessment. The milestones for year two will be randomization of 72 patients in the trial, retention for 13 weeks of 75% of subjects with completion of the week 13 follow-up MATRICS assessment, and retention for 26 weeks of 66% with completion of the week 26 follow- up MATRICS assessment. Schizophrenia affects approximately 3 million people in the US, and it is one of the leading causes of disability. PUBLIC HEALTH RELEVANCE: Currently available schizophrenia treatments are only partially effective, particularly for the cognitive impairments that underlie functional deficits associated with the illness. This research focuses on developing a new medication with cognition-enhancing and neuroprotective properties that when used together with existing medications may more effectively treat the cognitive and functional impairments of schizophrenia.