Human Laboratory Screening of Lorcaserin in Smokers with Alcohol Use Disorder

患有酒精使用障碍的吸烟者中氯卡色林的人体实验室筛查

• 批准号: 9752761
• 负责人: Eric D Claus
• 金额: $ 21.47万
• 依托单位: THE MIND RESEARCH NETWORK
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-10 至 2021-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9752761
• 关键词: Addictive Behavior; Agonist; Alcohol consumption; Alcohol dependence; Alcoholic beverage heavy drinker; Alcohols; Attenuated; Behavior; Behavioral; Cigarette; Cigarette Smoker; Clinical; Consumption; Cross-Over Studies; Cross-Over Trials; Data; Development; Dopamine; Double-Blind Method; Drug Receptors; Evaluation; FDA approved; Face; Health; Human; Impulsivity; Intervention; Investigation; Joints; Laboratories; Ligands; Measures; Motivation; National Institute on Alcohol Abuse and Alcoholism; Nicotine; Nicotine Dependence; Outcome; Outcome Measure; Participant; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase II Clinical Trials; Placebos; Play; Population; Pre-Clinical Model; Protocols documentation; Randomized Controlled Trials; Regulation; Relapse; Rewards; Risk; Role; Screening procedure; Selective Serotonin Reuptake Inhibitor; Self Administration; Serotonergic System; Serotonin; Serotonin Receptor 5-HT2C; Smoker; Smoking; Subgroup; Substance Use Disorder; Testing; Time; Translating; United States Food and Drug Administration; Weight maintenance regimen; addiction; alcohol abuse therapy; alcohol response; alcohol use disorder; base; behavior measurement; cancer risk; cigarette smoke; cigarette smoking; clinical risk; cost effective; craving; drinking; high risk; human data; indexing; individualized medicine; interest; new therapeutic target; nicotine use; novel; pre-clinical; preclinical study; randomized trial; response; screening; serotonin receptor; side effect; smoking cessation

PROJECT SUMMARY Pharmacotherapy development remains a critical objective for reducing health and societal burdens associated with alcohol use disorder (AUD). Developing targeted treatments for specific AUD subgroups is a key aim under the NIAAA medication development strategy. Among those with AUD, cigarette smokers comprise a sizable and critical subgroup with disproportionally high long-term health risks, making it a key priority to advance therapies for concurrent AUD and cigarette smoking. The serotonin (5-hydroxtytryptamine; 5-HT) system is broadly implicated in addictive behaviors, in part reflecting the role of 5-HT in modulating dopamine function. Preclinical studies of 5-HT receptor drugs have shown that targeted modulation of the 5-HT2C receptor (implicated in 5-HT-related inhibition of DA function) alters the consumption and reinstatement of addictive drugs, including alcohol and nicotine. Additionally, preclinical evidence shows that 5-HT2C receptor agonists attenuate behavioral indices of impulsivity. Of the selective 5-HT2C receptor agonists, lorcaserin has superior near-term potential for repurposing as an AUD therapy, having been approved by the Food and Drug Administration for weight management. A recent Phase II clinical trial supported efficacy of lorcaserin for smoking cessation; however, no human trials have examined lorcaserin's effects on alcohol-related outcomes or measures of impulsivity. Human laboratory medication trials offer a time- and cost-effective option for validating preclinical findings prior to larger randomized controlled trials, and for testing candidate treatment mechanisms. This application proposes a human laboratory screening trial to evaluate lorcaserin as a novel candidate therapy for smokers with AUD. The effects of lorcaserin vs. placebo will be evaluated in a double- blind, within-subjects, crossover study with human laboratory endpoints. This study will provide initial human data on the effects of a 5-HT2C receptor agonist in relation to alcohol-related outcomes, informing its potential for further evaluation as a candidate treatment for AUD.

项目概要 药物疗法的发展仍然是减少相关健康和社会负担的一个关键目标 患有酒精使用障碍（AUD）。开发针对特定 AUD 亚组的针对性治疗方法是一个关键目标 根据 NIAAA 药物开发战略。在持有澳元的人中，吸烟者包括 规模庞大且关键的亚群，具有不成比例的高长期健康风险，使其成为优先考虑的事项 针对 AUD 和吸烟同时发生的先进疗法。血清素（5-羟色胺；5-HT） 系统广泛涉及成瘾行为，部分反映了 5-HT 在调节多巴胺中的作用 功能。 5-HT受体药物的临床前研究表明，靶向调节 5-HT2C 受体（参与 5-HT 相关的 DA 功能抑制）改变消耗和恢复 成瘾药物，包括酒精和尼古丁。此外，临床前证据表明 5-HT2C 受体 激动剂减弱冲动的行为指数。在选择性 5-HT2C 受体激动剂中，氯卡色林 已获得美国食品药品监督管理局 (FDA) 的批准，近期具有重新用作 AUD 疗法的优越潜力 体重管理的管理。最近的一项 II 期临床试验支持了氯卡色林的功效 戒烟；然而，尚无人体试验检验氯卡色林对酒精相关结果的影响 或冲动的措施。人体实验室药物试验为以下患者提供了一种具有时间和成本效益的选择： 在更大规模的随机对照试验之前验证临床前发现，并测试候选治疗 机制。该申请提出了一项人体实验室筛选试验来评估氯卡色林作为一种新型药物 AUD 吸烟者的候选疗法。氯卡色林与安慰剂的效果将通过双重评估进行评估 与人类实验室终点进行盲法、受试者内交叉研究。这项研究将提供初步的人类 关于 5-HT2C 受体激动剂与酒精相关结果的影响的数据，揭示其潜力 作为 AUD 候选治疗的进一步评估。