Huperzine for Cognitive and Functional Impairment in Schizophrenia

描述（由申请人提供）：精神分裂症在美国影响了大约300万人，它是导致残疾的主要原因之一。目前可用的药物仅部分有效，特别是对于导致功能丧失的认知障碍。一种新的研究药物BMD-101在实验动物中被证明具有神经保护、神经营养、胆碱能和多巴胺能作用，并且在中国进行的有限临床试验中似乎有益于认知症状。这项研究将测试当BMD-101与现有药物一起使用时，是否会比现在更有效地治疗精神分裂症的认知和功能障碍。该方法的优点和可行性将在两年内通过一项随机、双盲、安慰剂对照、6个月的附加试验来确定，该试验将在72名精神分裂症患者中比较两种剂量的BMD-101和安慰剂，这些患者对目前的治疗没有最佳反应。这项试点研究的主要结果将是认知改善，由NIMH和fda开发的matrix电池评估。将评估一项共同主要功能结局指标，以满足FDA对治疗精神分裂症患者认知功能障碍适应症的要求。此外，安全性将通过不良事件报告、体格检查、生命体征、体重、心电图以及肝、肾、血液学和代谢功能的实验室检查来评估。效应大小和安全性的数据将指导确定疗效研究的设计。第一年的里程碑将在试验中随机分配48名患者，75%的受试者在完成第13周随访评估后保留13周，66%的受试者在完成第26周随访评估后保留26周。第二年的里程碑将是试验中72名患者的随机化，75%的受试者在完成第13周随访matrix评估后保留13周，66%的受试者在完成第26周随访matrix评估后保留26周。在美国，精神分裂症影响了大约300万人，它是导致残疾的主要原因之一。公共卫生相关性：目前可用的精神分裂症治疗仅部分有效，特别是对于与该疾病相关的功能缺陷的认知障碍。本研究的重点是开发一种具有认知增强和神经保护特性的新药，当与现有药物一起使用时，可能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.