Progesterone Therapy for Women with Epilepsy

描述（由申请人提供）：这项随机、安慰剂对照、双盲、多中心临床试验将评估辅助循环孕酮治疗在减少定位相关癫痫女性难治性癫痫发作频率方面的疗效。有相当多的科学证据表明，雌激素通常会增加，而黄体酮会降低神经元的兴奋性和癫痫发作。初步的公开试验表明，在大多数双侧加重的难治性癫痫发作的妇女中，周期性给药辅助天然孕酮补充剂可使癫痫发作频率降低50%以上。相比之下，口服合成黄体酮并没有显示出显著的疗效。黄体酮没有被广泛使用，因为它的益处还没有得到最终的证明。我们已经证明了黄体酮试验的可行性和安全性，在这项研究的初始阶段使用了150名受试者。我们现在建议着手完成对640名受试者的最终调查。在基线期，癫痫发作和月经图表记录了基线癫痫发作频率，并确定癫痫发作是否表现出一种急性发作模式。然后将研究对象分为双层地层和非双层地层。每个地层按2:1的比例随机分为黄体酮组和安慰剂组。治疗3个月期间癫痫发作频率与基线比较，同时监测抗癫痫药物和激素水平。该临床试验对女性癫痫患者具有相当大的潜在意义。尽管使用抗癫痫药物，约30%的患者仍持续发作。据估计，这些妇女中有35%有癫痫发作加重。如果这组人对激素治疗反应良好，我预计黄体酮可能受益约1,000,000倍。30倍。35) 10万名患有先天性癫痫的妇女以及可能更多的没有先天性癫痫的妇女表现出对癫痫发作的激素敏感性。

DESCRIPTION (provided by applicant): This randomized, placebo-controlled, double-blind, multicenter clinical trial will assess the efficacy of adjunctive cyclic progesterone therapy in lessening the frequency of intractable seizures in women with localization-related epilepsy. There is considerable scientific evidence to suggest that estrogen generally increases while progesterone decreases neuronal excitability and seizures. Preliminary open trials suggest that the cyclic administration of adjunctive natural progesterone supplement may lessen seizure frequency by over 50% in the majority of women with catamenially exacerbated intractable seizures. Oral synthetic progestins, in contrast, have not shown significant efficacy. Progesterone is not widely prescribed because its benefits have yet to be conclusively demonstrated. We have shown the feasibility and safety of a progesterone trial, using 150 subjects in the initial phase of this investigation. We now propose proceeding with the completion of this definitive investigation of 640 subjects. During the baseline phase, seizure and menstrual charts document baseline seizure frequency and determine if seizure occurrence shows a catamenial pattern of exacerbation. The subjects are then divided into catamenial and non-catamenial strata. Each stratum is randomized in a 2:1 ratio into progesterone and placebo treatment groups. Seizure frequency during 3 months of treatment is compared to baseline, while monitoring antiepileptic drug and hormone levels. This clinical trial has considerable potential significance for women with epilepsy. Approximately 30% have persistent seizures despite antiepileptic drug use. It is estimated that 35% of these women have catamenial seizure exacerbation. If this group responds favorably to hormonal therapy, 1 would expect that progesterone may benefit approximately (1,000,000 x .30 x .35) 100,000 women with catamenial epilepsy and perhaps many more women with no a priori demonstrated hormonal sensitivity to seizure occurrence.