A Randomized Controlled Trial of Exenatide as an Adjunct to Nicotine Patch for Smoking Cessation and Prevention of Post-Cessation Weight Gain

艾塞那肽作为尼古丁贴片辅助戒烟和预防戒烟后体重增加的随机对照试验

• 批准号: 10367010
• 负责人: CHRISTOPHER D VERRICO
• 金额: $ 60.24万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367010
• 关键词: Abstinence; Address; Aftercare; Agonist; American; Amphetamines; Attenuated; Biochemical; Body Weight; Brain; Bupropion; Carbon Monoxide; Cause of Death; Cessation of life; Chronic Disease; Cigarette; Clinical; Cocaine; Combined Modality Therapy; Counseling; Cues; Data; Diabetes Mellitus; Disease; Double-Blind Method; Double-blind trial; Energy Intake; Enrollment; Ensure; Event; Event-Related Potentials; Food; Fright; GLP-I receptor; Goals; Health; Hyperglycemia; Individual; Light; Measures; Metabolic; Metabolic syndrome; Morbidity - disease rate; Nicotine; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome Measure; Outcome Study; Overweight; Patient Self-Report; Persons; Pharmaceutical Preparations; Phase III Clinical Trials; Pilot Projects; Placebos; Prediabetes syndrome; Prevalence; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Relapse; Reporting; Research; Research Personnel; Resources; Rewards; Risk Factors; Sample Size; Scientist; Site; Smoker; Smoking; Smoking Cessation Intervention; Smoking Prevention; Stimulus; Testing; Time; Tobacco Use Disorder; Tobacco use; Vulnerable Populations; Weight; Weight Gain; Woman; Work; alcohol effect; attenuation; cigarette smoke; cigarette smoking; dietary; disability; emotional stimulus; exenatide; exercise program; improved; innovation; mortality; nicotine patch; nicotine replacement; novel; novel strategies; obesity risk; placebo controlled study; pre-clinical; preclinical study; premature; primary outcome; recruit; relapse risk; response; smoking abstinence; smoking cessation; varenicline

PROJECT ABSTRACT Despite reductions in prevalence over the last few decades, over 34 million Americans currently smoke cigarettes, and tobacco use remains the leading preventable cause of death, disability, and disease. Among smokers who achieve abstinence, post-cessation weight gain (PCWG) is common and attributed to increased energy intake in the first weeks and months after quitting. PCWG is problematic for three reasons. First, many smokers, especially women, report fear of PCWG as a major barrier to quitting. Second, PCWG can precipitate a relapse. Third PCWG can contribute to the onset of a chronic illness, such as obesity or type 2 diabetes mellitus. First-line treatments, i.e. nicotine replacement therapies (NRT), varenicline and bupropion help people quit smoking but do not provide a clinically meaningful impact on PCWG. Our recent pilot work showed that a 6-week treatment with a glucagon-like peptide-1 receptor (GLP-1R) agonist, extended-release exenatide, as an adjunct to nicotine patch, improved abstinence and decreased PCWG in prediabetic and/or overweight treatment-seeking smokers. These findings, which are consistent with preclinical reports that GLP-1R agonists decrease the rewarding effects of nicotine and food, support GLP-1R as a promising target for facilitating smoking cessation and decreasing PCWG. The proposed research will assess the efficacy of extended-release exenatide as an adjunct to nicotine patch on smoking abstinence and PCWG during the first 3 months after quitting, when most weight gain occurs. A double-blind trial is proposed in which treatment-seeking smokers will be randomized to receive either 2 mg exenatide (once a week) or placebo as an adjunct to nicotine patch for 14 weeks, starting 2 weeks prior to target quit day. The primary outcome measures will be end-of-treatment smoking abstinence (4-week continuous) and PCWG. We predict that exenatide will improve abstinence and mitigate PCWG relative to placebo. Exploratory aims will examine the long-term (6 months) impact of exenatide on the primary study outcomes and the effect of exenatide on neuroaffective responses to food- and nicotine-related stimuli. Innovative aspects of this research include: 1) targeting GLP-1R to facilitate smoking cessation and decrease PCWG; 2) testing an approved medication that could be deployed quickly as an adjunctive treatment for use in combination with NRT; 3) providing the impetus for conducting pivotal Phase 3 clinical trials to establish the efficacy of exenatide-NRT combinations and 4) exploring a putative mechanism implicated in exenatide's effects on smoking and PCWG. This project stands to contribute significantly to current treatments for smoking cessation by identifying a first-in-class adjunct pharmacotherapeutic that uniquely targets both cessation and weight gain. This R01 resubmission application is proposed by an early- stage investigator who has assembled a team of scientists with relevant expertise and access to resources, including two-site recruitment capabilities, to ensure timely enrollment and successful completion of a large sample size (N=216).

项目摘要 尽管过去几十年中的患病率降低了，但目前有超过3400万美国人吸烟 香烟和烟草使用仍然是可预防的死亡，残疾和疾病的主要原因。之中 实现禁欲的吸烟者，结尾体重增加（PCWG）很常见，归因于增加 退出后的头几周和几个月，能量摄入量。 PCWG有问题，原因有三个。首先，很多 吸烟者，尤其是女性，报告对PCWG的恐惧是戒烟的主要障碍。其次，PCWG会沉淀 复发。第三个PCWG可以导致慢性疾病的发作，例如肥胖或2型糖尿病 Mellitus。一线疗法，即尼古丁替代疗法（NRT），Varenicline和Bupropion帮助 人们戒烟，但对PCWG没有临床意义的影响。我们最近的飞行员工作显示 用胰高血糖素样肽-1受体（GLP-1R）激动剂进行6周的治疗，延长释放艾鉴定， 作为尼古丁补丁的辅助手段，糖尿病前期和/或超重的戒酒和PCWG降低 寻求治疗的吸烟者。这些发现与GLP-1R激动剂的临床前报告一致 减少尼古丁和食物的奖励作用，支持GLP-1R作为促进的有希望的目标 戒烟并减少PCWG。拟议的研究将评估扩展释放的功效 亚烯酰胺作为尼古丁贴剂在戒烟和PCWG上的辅助 退出，当大多数体重增加时。提出了双盲试验，在其中寻求治疗的吸烟者 将随机分配接受2 mg艾烯酸酯（每周一次）或安慰剂作为尼古丁补丁的辅助 14周，从目标退出日前2周开始。主要结果指标将是治疗的结束 戒烟（4周连续）和PCWG。我们预测，艾烯酰胺将改善戒酒和 减轻PCWG相对于安慰剂。探索目的将检查长期（6个月）的影响 亚鉴定对主要研究结果以及艾烯二胺对食物和食物的神经影响反应的影响 尼古丁相关的刺激。这项研究的创新方面包括：1）针对GLP-1R促进吸烟 停止并减少PCWG； 2）测试可以快速部署的批准药物 与NRT结合使用的辅助治疗； 3）提供进行关键阶段3的动力 临床试验以建立Atenatide-NRT组合的功效和4）探索假定的机制 与艾韦替代对吸烟和PCWG的影响有关。该项目将为 通过识别第一类辅助药物治疗方法的当前戒烟治疗方法 独特的靶向戒烟和体重增加。此R01重新提交申请由早期提出 舞台调查员召集了一个科学家团队，具有相关的专业知识和资源访问权限， 包括两个站点的招聘能力，以确保及时入学和成功完成大型 样本尺寸（n = 216）。