Phase 2 Study of 4-Aminopyridine for the Treatment of Episodic Ataxia Type 2

4-氨基吡啶治疗 2 型阵发性共济失调的 2 期研究

• 批准号: 8022784
• 负责人: JOANNA C JEN
• 金额: $ 19.99万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-15 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8022784
• 关键词: Phase; Study; Aminopyridine; Treatment; Episodic

DESCRIPTION (provided by applicant): Familial episodic ataxia (EA) syndromes are rare and heterogeneous monogenic disorders characterized by dramatic episodes of imbalance and uncoordination. Episodic ataxia type 2 (EA2) is the most common and the best characterized of all the EA syndromes. EA2 caused by mutations in CACNA1A (a neuronal calcium channel gene) typically presents with early onset debilitating ataxia episodes variably associated with nystagmus, headaches, and fluctuating weakness. Since the discovery of dramatic response of EA2 to acetazolamide, acetazolamide has been the first-line treatment for EA2. Yet, some patients are not responsive to acetazolamide, cannot tolerate the side effects, or are allergic to acetazolamide. For these patients (roughly a third of individuals who are currently participating in an ongoing UCLA Episodic Ataxia study as well a collaborative study with the University of Rochester), there are no alternative treatments. 4-Aminopyridine (4AP) was found in Europe to be effective in a few patients with EA2, and an extended release formulation of 4AP by Acorda Therapeutics has just been approved by the FDA in January 2010 for use in patients with multiple sclerosis. With assurance from Acorda to supply 4AP and placebo, a randomized trial is proposed to test the efficacy of 4AP in reducing ataxia episode frequency and secondarily to evaluate its tolerability and its impact on treatment satisfaction and health-related quality of life in patients with EA2. Recruitment of 20 subjects for this 3-year, double-blind, two-crossover, randomized trial of 4AP is proposed.

描述（由申请人提供）： 家族性发作性共济失调（EA）综合征是一种罕见的异质性单基因疾病，其特征是剧烈的不平衡和不协调发作。 发作性共济失调2型（EA 2）是所有EA综合征中最常见和最具特征的。由CACNA1A（一种神经元钙通道基因）突变引起的EA2通常表现为早发性衰弱性共济失调发作，与眼球震颤、头痛和波动性虚弱相关。自从发现EA2对乙酰唑胺的显著反应以来，乙酰唑胺一直是EA2的一线治疗药物。然而，一些患者对乙酰唑胺没有反应，不能耐受副作用，或者对乙酰唑胺过敏。对于这些患者（大约三分之一的人目前正在参加正在进行的加州大学洛杉矶分校发作性共济失调研究以及与罗切斯特大学的合作研究），没有替代治疗。4-在欧洲发现氨基吡啶（4AP）对少数EA2患者有效，Acorda Therapeutics的4AP缓释制剂刚刚于2010年1月获得FDA批准用于多发性硬化症患者。在Acorda保证提供4AP和安慰剂的情况下，提出了一项随机试验，以测试4AP在降低共济失调发作频率方面的疗效，其次是评估其耐受性及其对EA 2患者治疗满意度和健康相关生活质量的影响。拟招募20例受试者进行为期3年的4AP双盲、双交叉、随机试验。