Extended-Release Mixed Amphetamine Salts for Adults ADHD and Cocaine Dependence

描述(由申请人提供)：未经治疗的注意力缺陷/多动障碍(ADHD)是残疾的，其症状和后遗症会产生终生后果，例如，学习成绩受损和更高的物质使用障碍(SUD)率。到目前为止，兴奋剂是治疗儿童和成人ADHD的最有效的方法。同样，对可卡因的依赖会产生有问题的个人、社会和经济后果。目前还没有被批准的治疗可卡因依赖的药物，但越来越多的证据表明，类似激动剂的方法可能会带来好处。到目前为止，对成年可卡因依赖ADHD患者的速释和缓释哌醋甲酯的研究结果喜忧参半，这表明可能需要大剂量的长效苯丙胺制剂。在这里，我们建议测试两剂缓释混合苯丙胺盐(ER-MAS)，用于治疗患有ADHD的可卡因依赖者。我们之所以选择ER-MAS，是因为它的作用时间相对较长，而且在成人ADHD人群中具有耐受性。我们将进行一项为期12周的两点、三臂、双盲随机临床试验，比较安慰剂、60 mg ER-MAS和80 mg ER-MAS。每个地点将有25名患有ADHD的可卡因依赖者(地点总数：75人，每组25名受试者；总人数：150人，50人/组)。主要目标将包括：1.测量在ER-MAS(每天60或80毫克)缓释和PBO治疗期间可卡因使用的变化。假设：苯甲酰肾上腺素阳性尿检将减少，从80 mg；60 mg；PBO减少最多到最少。在ER-MAS(60或80 mg/d)缓释和PBO治疗期间测量ADHD症状的改善。假设：ADHD评定量表将从80 mg；60 mg；PBO下降到最大到最小。次要目标将是：1。测量作为ER-MAS和PBO的函数的一般功能CGI。假设：与PBO相比，接受右旋安非他明治疗的参与者的CGI评分将有更大的改善。测量ER-MAS与PBO期间冲动性的变化。假设：与PBO相比，ER-MAS将降低几个自我报告(Barretts冲动性量表)和行为测量(Card Sort，IMT，DMT，BART)所衡量的冲动性。这是一个几乎独一无二的机会，可以用一种药物治疗两种疾病，即ADHD和可卡因依赖，希望能改善这一难以治疗的人群的治疗结果。

DESCRIPTION (provided by applicant): Untreated attention-deficit/hyperactivity disorder (ADHD) is disabling and has life long consequences that emerge from its symptoms and sequelae, e.g., impaired school performance and higher substance use disorder (SUD) rates. To date, stimulant medications are the most effectively way to treat both childhood and adult ADHD. Similarly, cocaine dependence generates problematic individual, social, and economic consequences. There are no approved medications for the treatment of cocaine dependence, but accruing evidence suggests that an 'agonist'-like approach may provide benefit. To date studies of immediate and sustained-release methylphenidate for adult cocaine-dependent individuals with ADHD have produced mixed results, suggesting that high doses of a long-acting amphetamine preparation might be required. Here we propose testing 2 doses of an extended-release mixed amphetamine salt (ER-MAS) for the treatment of cocaine-dependent individuals with ADHD. We have chosen ER-MAS because of its relatively long duration of action and its tolerability in adult ADHD populations. We will conduct a two-site, three-arm, double blind randomized 12 week clinical trial comparing placebo, 60 mg ER-MAS, and 80 mg ER-MAS. There will be 25 cocaine dependent individuals with ADHD at each site (Site total: 75, 25 subject's per group; total N: 150, 50/group). Primary aims will include: 1. Measure change in cocaine use during treatment with ER-MAS (60 or 80 mg per day) sustained release and PBO. Hypothesis: Benzoylecognine positive urine screens will decrease with greatest to least reductions from 80mg>60mg>PBO. Measure improvement of ADHD symptomatology during treatment with ER-MAS (60 or 80 mg per day) sustained release and PBO. Hypothesis: ADHD-Rating Scale will decrease with greatest to least reductions from 80mg>60mg>PBO. Secondary Aims will be: 1. Measure general function CGI as a function of ER-MAS and PBO. Hypothesis: There will be greater improved CGI scores in participants receiving dextroamphetamine compared to PBO. Measure changes in impulsivity during ER-MAS vs. PBO. Hypothesis: ER-MAS will decrease impulsivity as measured by several self-report (Barretts Impulsivity Scale) and behavioral measures (Card Sort, IMT, DMT, BART) compared to PBO. Here a nearly unique opportunity exists to treat two conditions, ADHD and cocaine dependence, with a single medication, hopefully leading to improved treated outcome in this difficult-to-treat population.