Dichlorphenamide vs Acetazolamide for Periodic Paralysis

本修订申请为两种碳酸酐酶抑制剂的多中心临床试验中的定期 在规划补助金R21 NS 39939- 01 A1的帮助下，为残疾人制定了一项计划。这笔赠款是由 因为碳酸酐酶抑制剂（CAI）乙酰唑胺（ACZ）和双氯芬酰胺（DCP）具有 多年来一直用于周期性麻痹（PP），但治疗是否会 预防慢性进行性虚弱，这种虚弱折磨PP患者。此外，还不知道是哪种药剂， ACZ或DCP对于预防发作和治疗/预防虚弱是优选的。只有10%的 患者维持DCP，这可能是优选的治疗。在过去的十年里， 许多PP的缺陷已经被确定，使得分子治疗的研究成为可能- 明确的PP患者。 我们提出了14个中心的随机对照试验来检验语用假设，即（1）DCP和ACZ 将降低高钾PP（HYP）和低钾PP的虚弱发作频率 (HOP)（2）DCP将改善力量-在两种PP中比ACZ或安慰剂更大程度上;（3）DCP 和ACZ将改善这两种类型PP的生活质量。这些试验也将检验解释性假设 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/DCP对电解质和酸碱状态的影响与处理有关 应答 计划中的HYP-HOP试验将：（1）开发PP的标准治疗方法;（2）捍卫建议 用于PP的长期治疗;（3）为DCP的监管批准提供数据，这对于 使其可用于临床使用;（4）为更广泛地了解通道功能障碍奠定基础， PP和大量的神经肌肉和CNS通道病;（5）提供临床资源， 与基础科学实验室合作，研究体内和体外通道病的病理机制。

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.