Efficacy and Safety of Galantamine for Dysfunction in Bipolar Disorder

加兰他敏治疗双相情感障碍功能障碍的疗效和安全性

• 批准号: 8137720
• 负责人: DAN VLAD IOSIFESCU
• 金额: $ 30.53万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-25 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8137720
• 关键词: Acute; Address; Advertisements; Anterior; Area; Biological; Bipolar Disorder; Brain; Brain imaging; Choline; Cholinesterase Inhibitors; Clinic; Clinical; Clinical Pharmacology; Clinical Research; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Data; Dementia; Depressed mood; Disease; Disease remission; Double-Blind Method; Enrollment; Epilepsy; Evaluation; Functional disorder; Galantamine; General Hospitals; Hippocampus (Brain); Hospitals; Impaired cognition; Impairment; Knowledge; Left; Magnetic Resonance Spectroscopy; Manic; Massachusetts; Measures; Membrane; Memory; Mood Disorders; Moods; Multiple Sclerosis; N-acetylaspartate; Neurocognitive; Neurons; Neuropsychological Tests; Occupations; Outcome; Patients; Performance; Pharmaceutical Preparations; Phase; Phospholipid Metabolism; Placebo Control; Placebos; Protons; Public Health; Randomized; Research; Rest; Safety; Study Subject; Symptoms; Temporal Lobe; Testing; Treatment Efficacy; Treatment outcome; base; burden of illness; cingulate gyrus; cognitive function; experience; functional disability; improved; innovation; placebo controlled study; programs; psychosocial; statistics; translational study

DESCRIPTION (provided by applicant): Cognitive impairment, and its associated psychosocial and vocational functional impairments, occurs in many patients with bipolar disorder even when mood symptoms are adequately treated. Despite its importance, no validated treatments exist for cognitive impairments in bipolar disorder. We propose to enroll 120 subjects with bipolar disorder in a 16-week randomized, double blind, placebo controlled study to assess the efficacy of galantamine (an acetyl cholinesterase inhibitor) for the treatment of functional and cognitive impairments in bipolar disorder. Before the onset of medication treatment and at the end of the study we will administer a battery of neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS) to measure N-acetylaspartate (NAA, a marker of neuronal viability) from the left and right hippocampus. We will use 1H-MRS data to investigate the relation between neuroprotective effects of galantamine (as reflected by NAA levels) and improvement of cognitive deficits in bipolar subjects. All clinical characterization of bipolar subjects, neuropsychological tests and treatment with galantamine or placebo will be conducted in the Bipolar Clinical and Research Program at Massachusetts General Hospital; magnetic resonance spectroscopy assessments will be performed at the Brain Imaging Center at McLean Hospital. We are particularly well prepared to undertake these studies as our research team uniquely combines expertise in clinical pharmacology research, neurocognitive and functional evaluations and magnetic resonance spectroscopy assessments in subjects with bipolar disorder. Demonstrating the efficacy and safety of galantamine for the treatment of cognitive and functional impairment in bipolar disorder will be a major advancement for a significant clinical and public health problem. This translational study will also explore the relationship between cognitive dysfunction and markers of neuronal viability in specific brain areas to allow us to better understand the pathophysiology of cognitive dysfunction in mood disorders.

描述（由申请人提供）：即使情绪症状得到充分治疗，许多双相情感障碍患者也会出现认知障碍及其相关的社会心理和职业功能障碍。尽管其重要性，但尚无针对双相情感障碍认知障碍的有效治疗方法。我们建议招募 120 名双相情感障碍受试者参加一项为期 16 周的随机、双盲、安慰剂对照研究，以评估加兰他敏（一种乙酰胆碱酯酶抑制剂）治疗双相情感障碍功能和认知障碍的疗效。在药物治疗开始之前和研究结束时，我们将进行一系列神经心理学测试和质子磁共振波谱 (1H-MRS)，以测量左右海马的 N-乙酰天冬氨酸（NAA，神经元活力的标志物）。我们将使用 1H-MRS 数据来研究加兰他敏的神经保护作用（由 NAA 水平反映）与双相情感障碍受试者认知缺陷改善之间的关系。双相情感障碍受试者的所有临床特征、神经心理学测试以及加兰他敏或安慰剂治疗都将在马萨诸塞州总医院的双相情感障碍临床和研究项目中进行；磁共振波谱评估将在麦克莱恩医院的脑成像中心进行。我们为开展这些研究做好了充分准备，因为我们的研究团队独特地将双相情感障碍受试者的临床药理学研究、神经认知和功能评估以及磁共振波谱评估方面的专业知识结合起来。证明加兰他敏治疗双相情感障碍认知和功能障碍的有效性和安全性将是解决重大临床和公共卫生问题的重大进步。这项转化研究还将探索特定大脑区域的认知功能障碍与神经元活力标记物之间的关系，以便我们更好地了解情绪障碍中认知功能障碍的病理生理学。