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连续性环孕酮治疗在减少局部相关性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，雌激素通常增加，而孕酮降低神经元的兴奋性和癫痫发作。初步的开放试验表明，周期性服用天然孕酮补充剂可以减少癫痫发作频率超过50%，在大多数妇女与catamenially加剧顽固性癫痫发作。相反，口服合成孕激素没有显示出显著的疗效。预后并没有被广泛规定，因为它的好处还没有得到最终证明。我们已经证明了孕激素试验的可行性和安全性，在本研究的初始阶段使用了150名受试者。我们现在建议继续完成对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基线癫痫发作频率，并确定癫痫发作是否显示月经性加重模式。然后将受试者分为月经和非月经阶层。每层以2：1的比例随机分为孕酮和安慰剂治疗组。将治疗3个月期间的癫痫发作频率与基线进行比较，同时监测抗癫痫药物和激素水平。这项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，仍有约30%的患者持续癫痫发作。据估计，这些妇女中有35%有月经性癫痫发作加重。如果这一组对激素治疗反应良好，我预计孕酮可能会使大约（1，000，000 × 0.30 × 0.35）100，000名月经期癫痫妇女受益，也许还有更多的妇女没有先验证明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.