Neurocognitive Effects of Opiate Agonist Treatment in HIV Infected Drug Users

阿片激动剂治疗对 HIV 感染吸毒者的神经认知影响

• 批准号: 8516487
• 负责人: JULIA H. ARNSTEN
• 金额: $ 65.88万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516487
• 关键词: Adult; Affect; Aftercare; Agonist; American; Brain; Buprenorphine; Clinical Trials Design; Dementia; Disease; Drug Addiction; Drug Interactions; Drug usage; Drug user; Enrollment; Ensure; Epidemiology; Exhibits; Frequencies; Functional disorder; HIV; HIV Infections; Health Personnel; Highly Active Antiretroviral Therapy; Impairment; Improve Access; Longitudinal Studies; Maintenance Therapy; Measures; Methadone; Neurocognitive; Neurocognitive Deficit; Opiate Addiction; Opiates; Opioid; Outcome; Patients; Performance; Persons; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Randomized; Randomized Clinical Trials; Recommendation; Recording of previous events; Relative (related person); Research; Risk; Role; Running; Severities; Testing; Therapeutic; Time; Treatment outcome; United States Food and Drug Administration; adverse outcome; arm; design; experience; follow-up; improved; kappa opioid receptors; longitudinal design; methadone maintenance; mild neurocognitive impairment; motor deficit; mu opioid receptors; substance abuse treatment; treatment effect

DESCRIPTION (provided by applicant): Rates of HIV-associated neurocognitive (NC) disorders remain high, despite the emergence of HAART. HIV-infected drug users exhibit accelerated and more severe NC dysfunction than either HIV-infected persons without drug use histories, or uninfected drug users. Because the risk of NC impairment is also elevated in opioid users regardless of HIV-status, there is additive risk of NC impairment for HIV-infected opioid users. How medications commonly used to treat opioid dependence affect the progression NC dysfunction is poorly understood. Methadone is the most commonly used medication for opioid addiction treatment, and some studies suggest that methadone, a full mu opioid receptor agonist, may be associated with NC deficits. However, these studies have largely lacked longitudinal follow-up to assess whether long-term methadone maintenance is associated with progression of NC dysfunction. Further, despite its therapeutic benefits, methadone is under- utilized, with only 12% of opioid-dependent Americans receiving methadone in 2005. To remedy this, buprenrophine was approved for opioid addiction treatment in 2002. Buprenorphine, a partial mu opioid receptor agonist and kappa opioid receptor antagonist, may have favorable NC effects compared to methadone. However, few studies have examined buprenorphine's NC effects, and none have included longitudinal follow-up or focused on HIV-infected persons. To ensure that treatment providers understand the full range of buprenorphine's effects, it is crucial to evaluate the relative NC effects of buprenorphine and methadone in opioid users with and without HIV infection. In this revised application, we propose to use a randomized clinical trial (RCT) design to test the hypothesis that treatment with buprenorphine is associated with significant improvement in NC function in opioid-dependent drug users with- and with- out HIV, compared to methadone. We will also examine whether HIV-infection moderates the impact of opioid agonist therapies on NC function. We will enroll and randomize 160 subjects 1:1 to 6 months of buprenorphine or methadone treatment, both of which will be delivered in the same supervised setting by experienced substance abuse treatment physicians. We will stratify randomization by HIV-serostatus, to ensure equal numbers of HIV-infected subjects in each arm. Following randomization and a one week run-in, we will measure NC function with a state-of-the art NC battery. We will then repeat the NC battery after 3 and 6 months of opioid agonist treatment. Our specific aims are: (1) to determine, in an RCT, whether buprenorphine is associated with significant improvement in NC function compared to methadone; (2) to assess the impact of buprenorphine treatment on change in NC function over time; and (3) to assess the impact of methadone treatment on changes in NC function over time. This will be the first randomized longitudinal trial investigating the impact of methadone and buprenorphine on neurocognitive outcomes. Findings from this study have the potential to impact treatment recommendations for opioid dependence for drug users with or without HIV, to improve NC outcomes, and to deepen our understanding of brain-drug interactions.

描述（由申请人提供）：尽管出现了HAART，但与HIV相关的神经认知（NC）疾病的发生率仍然很高。与没有药物使用历史的HIV感染者或未感染的吸毒者相比，感染HIV的吸毒者表现出加速和严重的NC功能障碍。由于阿片类药物用户的NC损伤风险也会升高，无论HIV状态如何，因此HIV感染的阿片类药物使用者存在NC损害的添加剂风险。对治疗阿片类药物依赖性治疗的药物如何影响NC功能障碍的进展知之甚少。 美沙酮是阿片类药物成瘾治疗的最常用药物，一些研究表明，美沙酮是一种完整的MU阿片受体激动剂，可能与NC缺陷有关。但是，这些研究在很大程度上缺乏纵向随访，以评估长期美沙酮维持是否与NC功能障碍的进展有关。此外，尽管具有治疗益处，但美沙酮仍在使用，只有12％的阿片类药物依赖性美国人在2005年接受美沙酮。为了补救这种疗法，丁丙诺罗汀在2002年获得了阿片类药物成瘾治疗。在2002年，丁丙诺氨酸，部分Mu opioid受体受体和kappa aponist和kappa apodor aptogogain aptagogogan natcy to Medagogon ancone to Mer Medagon to Mer Medagogon anc Optia to Mer Medagon。但是，很少有研究检查了丁丙诺啡的NC效应，没有研究包括纵向随访或关注感染HIV的人。为了确保治疗提供者了解丁丙诺啡的全部效果，这是至关重要的 评估丁丙诺啡和美沙酮在患有和没有HIV感染的阿片类药物使用者中的相对NC效应。 在此修订后的应用中，我们建议使用随机临床试验（RCT）设计来检验以下假设：丁丙诺啡治疗与与美沙酮相比，与HIV相比，与HIV的阿片类药物依赖性药物使用者在NC功能的显着改善有关。我们还将检查HIV感染是否缓和了阿片类动力学疗法对NC功能的影响。我们将注册和随机分配160名受试者1：1至6个月的丁丙诺啡或美沙酮治疗，这两者都将在经验丰富的药物滥用治疗医生的同一监督环境中进行。我们将通过HIV-Serostatus对随机进行分层，以确保每个手臂中的HIV感染受试者相等。随机分组和一周的磨合后，我们将使用最先进的NC电池测量NC功能。然后，我们将在3个月和6个月的阿片类激动剂治疗后重复NC电池。我们的具体目的是：（1）在RCT中确定丁丙诺啡是否与美沙酮相比是否与NC功能的显着改善相关； （2）评估丁丙诺啡治疗对NC功能随时间变化的影响； （3）评估美沙酮处理对随着时间的变化的影响。 这将是首次研究美沙酮和丁丙诺啡对神经认知结果的影响的随机纵向试验。这项研究的发现有可能影响治疗建议对艾滋病毒或没有艾滋病毒的吸毒者的治疗建议，以改善NC结果，并加深我们对脑毒性相互作用的理解。