CBT and Modafinil for Cocaine Addiction

描述（由申请人提供）：迄今为止，尚未发现一种有效的药物治疗可卡因依赖。本试验提出认知行为疗法（CBT）作为社会心理平台，比较两种剂量的莫达非尼和安慰剂治疗可卡因成瘾。莫达非尼是一种上市的非典型兴奋剂，已被FDA批准用于治疗癫痫症。莫达非尼作用于下丘脑前部的几个核细胞内，促进皮层激活，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，改善情绪，提高注意力/集中力，降低食欲。一些临床前人体试验表明莫达非尼的滥用可能性很低。莫达非尼的副作用是适度的，莫达非尼与可卡因、安非他明或哌甲酯没有药代动力学相互作用。在我们组的一项人体实验室研究中（n=12），莫达非尼400和800毫克对低剂量（20毫克）和高剂量（40毫克）静脉注射可卡因都抑制了主观的“高”、“药物效果”和“愿意为高支付的金额”。我们假设莫达非尼作为非典型激动剂替代治疗可卡因。莫达非尼可改善可卡因戒断症状，钝化可卡因“高”的多维度，增强CBT的益处。为了验证这些假设和莫达非尼的安全性，我们建议进行为期两周的筛选基线期，然后进行为期八周的莫达非尼每日200mg、400mg和安慰剂的随机平行研究。随访将在所有治疗停止后的4周和8周进行。结果测量将包括不使用可卡因的天数和连续不使用可卡因的天数，由自我报告评估，并将通过每周一次的苯甲酰ecgonine尿检来确认。二次评估将包括情绪、白天嗜睡、可卡因戒断和可卡因“高”的主观方面的测量。通过定量尿核黄素水平和血清莫达非尼水平来评估安慰剂和研究药物的依从性。安全性将通过自我报告和反复体检、实验室研究、心电图以及独立数据安全监测委员会的监测来评估。

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.