Neurocysticercosis: Combined Treatment with Praziquantel and Albendazole

描述（由申请人提供）：猪带绦虫脑囊虫病是世界上获得性癫痫发作的唯一主要原因，也是美国和其他工业化国家移民人群的常见诊断。我们已经证明，通过使用抗寄生虫治疗杀死脑囊肿可以改善相关癫痫发作疾病的预后。囊肿死亡不是药物的直接结果，而是由于宿主的免疫系统在治疗相关损伤引起的抗原暴露后破坏寄生虫而导致的。目前的抗寄生虫治疗方案仅提供部分疗效，杀死75%或更少的脑囊肿。我们假设，两种不同抗寄生虫药物的联合治疗将提高脑寄生虫的清除率，从而提供更好的杀囊肿疗效，并将进行双盲，一项随机临床试验，以确定吡喹酮（PZQ）和阿苯达唑（ABZ）的10天联合方案是否在相同的剂量和治疗时间长度下，提高了单独使用ABZ的杀寄生虫功效。另一个要检查的目的是，在18个月的随访期内，囊肿完全破坏（没有任何存活囊肿的患者）是否与癫痫发作次数减少有关。将有两项相关的子研究：i）ABZ和PZQ在脑囊虫病患者中的药代动力学，和ii）治疗脑囊虫病后完全治愈的免疫学标志物。母研究将确定联合抗寄生虫治疗在杀寄生虫效果和控制癫痫发作方面的获益。这种治疗模式将在世界范围内适用。这两项子研究应增加关于药物药代动力学的有用数据，并评估早期预测完全治愈的可能性。

DESCRIPTION (provided by applicant): Taenia solium neurocysticercosis is the single major cause of acquired epileptic seizures in the world, and a common diagnosis in immigrant populations in the USA and other industrialized countries. We have demonstrated that the prognosis of the associated seizure disorder improves by killing brain cysts using anti-parasitic treatment. Cyst death is not the direct result of the drug but actually results from the host's immune system destroying the parasite after antigenic exposure caused by treatment-associated damage. Current regimes of antiparasitic treatment offer only partial efficacy, killing 75% of brain cysts or less. We hypothesize that combined treatment with two different anti-parasitic drugs will improve clearance of brain parasites and thus provide better cysticidal efficacy, and will perform a double-blind, randomized clinical trial to determine if a 10-days combined regime of regime of praziquantel (PZQ) and albendazole (ABZ) improves the parasiticidal efficacy of ABZ alone at the same dose and length of treatment. A secondary aim to be examined is also whether complete cyst destruction (patients free of any viable cysts) is associated with fewer seizures in a 18-months follow up period. There will be two associated substudies: i) pharmacokinetics of ABZ and PZQ in patients with neurocysticercosis, and ii) immunological markers of complete cure after treatment for neurocysticercosis. The parent study will determine the benefits of combined antiparasitic therapy in terms of parasiticidal effect and control of seizures. This mode of therapy would have worldwide applicability. The two sub-studies should add useful data on the pharmacokinetics of the drugs and assess the possibility of early prediction of complete cure.