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，即使他们的健康状况稳定或通过抗逆转录病毒药物恢复。艾滋病毒感染者的疲劳与残疾和生活满意度下降有关，是那些考虑重返工作岗位的人的一个重大障碍。虽然在流行病的早期，疲劳归因于病毒和伴随的机会性感染，但最近似乎延长生命的抗逆转录病毒药物也发挥了作用。 我们小组和其他人以前的研究表明，艾滋病毒/艾滋病患者的疲劳对精神兴奋剂如苯丙胺和哌醋甲酯有反应。然而，由于医生不愿意开处方，这些药物的使用受到限制，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的。因此，对于HIV相关疲劳的有效治疗仍然存在显著未满足的需求。 我们建议进行一项为期4周的安慰剂对照双盲试验，莫达非尼的HIV+患者有临床意义的疲劳，随后是8周的维持期莫达非尼反应。莫达非尼被批准用于治疗发作性睡病，但其用途已扩展到治疗其他神经系统疾病或抑郁症患者群体的疲劳和白天过度嗜睡，并且研究结果是积极的。 我们计划入组120例患者，预计至少有100例患者完成研究。 主要目的涉及莫达非尼与安慰剂相比对疲劳的疗效，对免疫学/病毒学指标影响方面的安全性，以及对基线时存在的抑郁症状的影响。

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.