Dichlorphenamide vs Acetazolamide for Periodic Paralysis

双氯苯那胺与乙酰唑胺治疗周期性麻痹

• 批准号: 6846379
• 负责人: Robert C Griggs
• 金额: $ 120.83万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6846379
• 关键词: Acetazolamide; Acids; Award; Basic Science; Calcium; Carbonic Anhydrase Inhibitors; Chloride Ion; Chronic; Clinical; Clinical Treatment; Clinical Trials; Data; Defect; Diagnostic; Dichlorphenamide; Electrolytes; Frequencies; Functional disorder; Funding; Grant; Hyperkalemic periodic paralysis; Hypokalemic periodic paralysis; In Vitro; Individual; Ion Channel; Laboratories; Living Wills; Minority; Molecular; Molecular Diagnosis; Mutation; Numbers; Outcome; Paralysed; Patients; Pharmaceutical Preparations; Phase; Phenotype; Placebos; Potassium Chloride; Prevention; Preventive; Quality of life; Randomized; Randomized Controlled Trials; Recommendation; Resources; Sodium; Standards of Weights and Measures; Testing; Uncertainty; United States Food and Drug Administration; United States National Institutes of Health; Upper arm; Week; base; clinical phenotype; design; improved; in vivo; insight; muscle strength; placebo controlled study; prevent; response; treatment trial

This revised application for multicenter clinical trials of two carbonic anhydrase inhibitors in the periodic paralyses has been prepared with the help of planning grant R21 NS 39939-01A1. This grant was awarded because the carbonic anhydrase inhibitors (CAI) acetazolamide (ACZ) and dichlorphenamide (DCP) have been used in the periodic paralyses (PP) for many years but there is uncertainty whether treatment will prevent the chronic, progressive weakness that afflicts PP patients. Moreover, it is not known which agent, ACZ or DCP is preferable for attack prevention and treatment/prevention of weakness. Only 10% of patients are maintained on DCP, which may be preferred treatment. In the past decade, the molecular defects of many of the PP's have been identified, making possible the study of treatment in molecularly- defined patients with PP. We propose 14-center randomized controlled trials to test the pragmatic hypotheses that (1) DCP and ACZ will decrease the frequency of attacks of weakness in hyperkalemic PP (HYP) and in hypokalemic PP (HOP); (2) DCP will improve strength-to a greater extent than ACZ or placebo in both PP's; and (3) that DCP and ACZ will improve quality of life in both types of PP. The trials will also test the explanatory hypotheses that specific ion channel mutations will: (1) predict differing phenotypes and (2) predict differing responses to ACZ and DCP and that (3) ACZ/DCP effects on electrolyte and acid/base status are related to treatment responses. The planned HYP-HOP trials will: (1) develop standard treatments for the PP; (2) defend recommendations for long-term treatments in PP; (3) provide data for regulatory approval of DCP, which is essential to have it available for clinical use; (4) lay the groundwork for broader insight into channel dysfunction in the PP and a large number of neuromuscular and CNS channelopathies; (5) provide clinical resources for collaborating basic science laboratories to study pathomechanisms of channelopathies in vivo and vitro.

本修订申请针对两种碳酸酐酶抑制剂的定期多中心临床试验 瘫痪已在规划拨款 R21 NS 39939-01A1 的帮助下准备就绪。这笔补助金被授予 因为碳酸酐酶抑制剂 (CAI) 乙酰唑胺 (ACZ) 和二氯苯酰胺 (DCP) 具有 多年来一直用于治疗周期性麻痹（PP），但治疗是否有效尚不确定 预防 PP 患者出现的慢性进行性无力。此外，尚不清楚是哪个代理， ACZ或DCP更适合攻击预防和治疗/预防虚弱。仅占10% 患者维持 DCP，这可能是首选治疗。在过去的十年里，分子 许多 PP 的缺陷已被识别，使得分子治疗研究成为可能。 定义为 PP 患者。 我们提出 14 中心随机对照试验来检验以下实用假设：(1) DCP 和 ACZ 会减少高钾血症 PP (HYP) 和低钾血症 PP 中无力发作的频率 （跳）; (2) 在两种 PP 中，DCP 会比 ACZ 或安慰剂更大程度地提高强度； (3) DCP ACZ 将改善两种类型 PP 的生活质量。试验还将检验解释性假设 特定的离子通道突变将：（1）预测不同的表型和（2）预测不同的反应 ACZ 和 DCP 以及 (3) ACZ/DCP 对电解质和酸/碱状态的影响与治疗有关 回应。 计划中的 HYP-HOP 试验将： (1) 开发 PP 的标准治疗方法； (2) 辩护建议 用于 PP 的长期治疗； (3) 为DCP的监管审批提供数据，这对于 可供临床使用； (4) 为更广泛地了解通道功能障碍奠定基础 PP和大量神经肌肉和中枢神经系统通道病； (5) 提供临床资源 合作基础科学实验室研究体内和体外通道病的病理机制。