Modafinil Treatment for Fatigue in HIV+ Patients

描述(由申请人提供)：疲劳仍然是许多艾滋病毒/艾滋病患者的主要问题，即使他们的健康本来是稳定的或通过抗逆转录病毒药物恢复的。艾滋病毒的疲劳与残疾和生活满意度降低有关，对那些考虑重返工作岗位的人来说是一个重大障碍。虽然在疫情早期，疲劳被归因于病毒和随之而来的机会性感染，但最近似乎本来可以延长生命的抗逆转录病毒药物也发挥了作用。 我们小组和其他人之前的研究表明，艾滋病毒/艾滋病患者的疲劳与精神刺激剂如右旋苯丙胺和哌醋甲酯有关。然而，由于医生不愿开这些药物，这些药物的获得受到限制，剂量增加往往是必要的，对于有药物滥用史的患者，它们在很大程度上是禁忌。因此，对艾滋病毒相关疲劳症的有效治疗仍然存在大量未得到满足的需求。 我们建议进行为期4周的安慰剂对照的莫达非尼双盲试验，用于临床上有显著疲劳感的HIV患者，随后对莫达非尼应答者进行为期8周的维持阶段。莫达非尼被批准用于治疗发作性睡病，但它的使用已扩大到治疗其他患有神经系统疾病或抑郁症的患者组的疲劳和日间过度嗜睡，结果是积极的。我们计划进入120名患者，预计至少有100名研究完成者。主要目标涉及莫达非尼与安慰剂相比对疲劳的疗效，在免疫学/病毒学措施方面的影响方面的安全性，以及在基线状态下对抑郁症状的影响。

DESCRIPTION (provided by applicant): Fatigue continues to be a major problem for many people with HIV/AIDS, even when their health is otherwise stable or restored by antiretroviral medication. Fatigue in HIV is associated with disability and diminished life satisfaction, and is a significant barrier for those who consider returning to work. While earlier in the epidemic, fatigue was attributed to the virus and concomitant opportunistic infections, more recently it seems that the otherwise life-extending antiretrovirals also play a role. Previous research by our group and others has demonstrated that fatigue in patients with HIV/AIDS is responsive to psychostimulants such as dextroamphetamine and methylphenidate. However, access to these drugs is limited by physician reluctance to prescribe them, dose escalation is often necessary, and for patients with substance abuse histories they are largely contraindicated. Consequently, there remains a significant unmet need for an effective treatment for HIV-associated fatigue. We propose to conduct a 4-week placebo controlled double blind trial of modafinil for HIV+ patients with clinically significant fatigue, followed by an 8-week maintenance phase for modafinil responders. Modafinil is approved for the treatment of narcolepsy, but its use has been extended to treat fatigue and excessive daytime sleepiness in other patient groups with neurological disease or depression, and findings have been positive. We plan to enter 120 patients with the expectation of having at least 100 study completers. The major aims concern modafinil efficacy for fatigue compared to placebo, safety in terms of effects on immunologic/virologic measures, and impact on depressive symptoms when present at baseline.