Progesterone Therapy for Women with Epilepsy

描述(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环孕酮治疗在减少与定位相关的癫痫的女性难治性癫痫发作频率方面的效果。有相当多的科学证据表明，雌激素通常会增加，而孕酮会降低神经元的兴奋性和癫痫发作。初步开放试验表明，在大多数患有月经性难治性癫痫加重的女性中，周期服用辅助性天然孕酮补充剂可以减少50%以上的癫痫发作频率。相比之下，口服合成孕激素并没有显示出显著的疗效。黄体酮没有被广泛开出，因为它的益处还没有得到确凿的证明。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，我们使用了150名受试者。我们现在建议继续完成这项对640名受试者的最终调查。在基线阶段，癫痫发作和月经表记录基线癫痫发作频率，并确定癫痫发作是否表现出月经模式的恶化。然后将受试者分为月经期和非月经期。每层按2：1的比例随机分为黄体酮和安慰剂治疗组。在监测抗癫痫药物和激素水平的同时，将治疗3个月期间的癫痫发作频率与基线进行比较。这项临床试验对女性癫痫患者具有相当大的潜在意义。尽管使用了抗癫痫药物，大约30%的人仍有持续性癫痫发作。据估计，这些妇女中有35%患有月经性癫痫加重。如果这组人对激素治疗反应良好，人们预计孕酮将使大约(1,000,000 x.30 x.35)100,000名患有月经性癫痫的女性受益，也许更多没有先天病史的女性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.