Huperzine for Cognitive and Functional Impairment in Schizophrenia

石杉碱甲治疗精神分裂症认知和功能障碍

• 批准号: 7694314
• 负责人: Scott W Woods
• 金额: $ 24.6万
• 依托单位: BIOMEDISYN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7694314
• 关键词: Acetylcholinesterase; Acetylcholinesterase Inhibitors; Activities of Daily Living; Adverse event; Affect; Alkaloids; Alzheimer' s Disease; China; Chinese People; Clinical Trials; Cognition; Cognitive; Conduct Clinical Trials; Data; Dose; Double-Blind Method; Drug Prescriptions; Electrocardiogram; Health; Hepatic; Impaired cognition; Interview; Investigational Drugs; Isomerism; Kidney; Laboratories; Laboratory Animals; Marketing; Measures; Metabolic; National Institute of Mental Health; Neurobehavioral Manifestations; Nutraceutical; Outcome; Outcome Measure; Patients; Pharmaceutical Preparations; Phase; Pilot Projects; Placebo Control; Placebos; Property; Randomized; Reporting; Research; Research Personnel; Role; Safety; Sales; Schizophrenia; Small Business Technology Transfer Research; Testing; Translating; Weight; base; cholinergic; cognitive enhancement; commercial application; commercialization; design; dietary supplements; disability; efficacy testing; follow-up; functional disability; functional loss; functional outcomes; hatching; huperzine A; interest; meetings; primary outcome; public health relevance; trial comparing

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.

描述（由申请人提供）：精神分裂症影响着美国大约 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 已被证明对实验动物具有神经保护、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 BMD-101 与现有药物一起使用是否可以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开展一项随机、双盲、安慰剂对照、为期 6 个月的附加试验来确定，该试验在 72 名未接受过治疗的精神分裂症患者中比较了两种剂量的 BMD-101 和安慰剂。对当前治疗有最佳反应。这项试点研究的主要结果将是通过 NIMH 和 FDA 开发的 MATRICS 电池评估的认知改善。将评估共同主要功能结果指标，以满足 FDA 对治疗精神分裂症认知功能障碍适应症的要求。此外，还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来评估安全性。有关效应大小和安全性的数据将指导明确疗效研究的设计。第一年的里程碑将是随机化试验中的 48 名患者，75% 的受试者完成第 13 周随访 MATRICS 评估后保留 13 周，完成第 26 周后 66% 的受试者保留 26 周后续 MATRICS 评估。第二年的里程碑将是试验中随机分配 72 名患者，75% 的受试者完成第 13 周随访 MATRICS 评估后保留 13 周，完成第 26 周后 66% 的受试者保留 26 周后续 MATRICS 评估。在美国，精神分裂症影响着大约 300 万人，它是导致残疾的主要原因之一。公众健康相关性：目前可用的精神分裂症治疗方法仅部分有效，特别是对于与该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认知增强和神经保护特性的新药物，与现有药物一起使用可以更有效地治疗精神分裂症的认知和功能障碍。