Neurocysticercosis: Combined Treatment with Praziquantel and Albendazole

描述(申请人提供)：猪带绦虫脑囊虫病是世界上后天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口的常见诊断。我们已经证明，通过使用抗寄生虫治疗杀死脑囊肿，相关癫痫障碍的预后得到改善。囊性死亡不是药物的直接结果，而是宿主的免疫系统在抗原暴露后破坏寄生虫造成的治疗相关损害。目前的抗寄生虫治疗方案只能提供部分疗效，杀死75%或更少的脑囊肿。我们假设，两种不同的抗寄生虫药物联合治疗将改善脑寄生虫的清除，从而提供更好的杀囊效果，并将进行双盲随机临床试验，以确定在相同剂量和治疗时间下，为期10天的吡喹酮(PZQ)和阿苯达唑(ABZ)联合治疗是否提高了ABZ单独治疗的寄生虫杀灭效果。要检查的第二个目标还是，在18个月的随访期内，完全囊性破坏(没有任何可存活的囊性物的患者)是否与较少的癫痫发作有关。将有两个相关的子研究：i)ABZ和PZQ在脑囊虫病患者中的药代动力学，以及ii)脑囊虫病治疗后完全治愈的免疫学标志物。母公司的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好处。这种治疗模式将在全球范围内适用。这两个子研究应该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.