CBT and Modafinil for Cocaine Addiction

描述(申请人提供)：到目前为止，还没有发现有效的可卡因依赖的药物治疗方法。本试验建议认知行为疗法(CBT)作为心理社会平台，比较两种剂量的莫达非尼和安慰剂治疗可卡因成瘾的疗效。莫达非尼是一种上市的非典型兴奋剂，已被FDA批准用于治疗甲硝苯丙胺。莫达非尼作用于下丘脑前部几个核团的细胞内，以促进皮质激活，但不改变多巴胺系统。莫达非尼的对照试验表明，它可以减少嗜睡，提升情绪，提高注意力/注意力，并降低食欲。几项临床前人体试验表明，莫达非尼的滥用可能性很低。莫达非尼的副作用不大，莫达非尼与可卡因、安非他明或哌醋甲酯之间没有药代动力学相互作用。在我们小组的一项人体实验室研究中(n=12)，莫达非尼400和800毫克抑制了静脉注射可卡因的低剂量(20毫克)和高剂量(40毫克)的主观“高”、“药物效应”和“愿意为高水平付出的金额”。我们推测莫达非尼可作为可卡因的非典型激动剂替代疗法。莫达非尼应能改善可卡因戒断症状，减轻可卡因“兴奋”的多个维度，并增强CBT的益处。为了检验这些假设和莫达非尼的安全性，我们建议进行两周的筛查基准期，然后进行为期八周的随机平行研究，每天服用莫达非尼200毫克、400毫克和安慰剂。随访将在所有治疗停止后4周和8周进行。结果衡量标准将包括通过自我报告评估的不使用可卡因的天数和连续不使用天数，这些天数将通过每周三次尿液苯甲酰ecGonine定量化验得到确认。二级评估将包括情绪、白天嗜睡的测量，以及可卡因戒断和可卡因“兴奋”的主观方面。安慰剂和研究药物的依从性将通过定量的尿核黄素水平和血清莫达非尼水平进行评估。安全性将通过自我报告和反复体检、实验室研究、心电图和由独立的数据安全监测委员会进行监测相结合的方式进行评估。

DESCRIPTION (provided by applicant): Thus far, an effective pharmacologic treatment for cocaine dependence has not been discovered. The present trial proposes cognitive behavior therapy (CBT) as the psychosocial platform to compare two doses of modafinil with placebo for the treatment of cocaine addiction. Modafinil is a marketed, atypical stimulant which has been approved by the FDA for the treatment of nacrolepsy. Modafinil acts intracellularly in several nuclei in the anterior hypothalamus to promote cortical activation, but does not alter dopamine systems. Controlled trials with modafinil indicate that it decreases hypersomnolence, elevates mood, enhances attention/concentration, and decreases appetite. Several preclinical human trials indicate that abuse potential of modafinil is low. Side effect profile for modafinil is modest and modafinil does not have pharmacokinetic interactions with cocaine, amphetamines, or methylphenidate. In a human laboratory study (n=12) from our group, Modafinil 400 and 800 mg suppressed subjective "high," "drug effect," and "amount willing to pay for high" to both low doses (20 mg) and high doses (40 mg) of IV cocaine. We postulate that modafinil serves as an atypical agonist replacement therapy for cocaine. Modafinil should ameliorate the symptoms of cocaine abstinence, blunt multiple dimensions of the cocaine "high" and enhance benefits of the CBT. To test these hypotheses and the safety of modafinil, we propose a two week screening baseline period followed by an eight week randomized parallel study of modafinil 200 mg, 400 mg and placebo daily. Follow up will occur four and eight weeks after all therapies cease. Outcome measures will include the number of cocaine non-use days and consecutive non-use days as assessed by self-report that will be confirmed by urine assays for quantitative benzoylecgonine three times a week. Secondary assessments will include measures of mood, daytime sleepiness, and subjective aspects of cocaine withdrawal and cocaine "high." Compliance with placebo and study medications will be assessed by quantitative urine riboflavin levels and serum modafinil levels. Safety will be assessed by a combination of self-report and repeated physical examinations, laboratory studies, ECGs, and monitoring by an independent data safety monitoring board.