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: 10649417
• 负责人: CHRISTOPHER D VERRICO
• 金额: $ 54.84万
• 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/10649417
• 关键词: Abstinence; 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, Controlled Trials; Relapse; Reporting; Research; Research Personnel; Resources; Rewards; Risk Factors; Risk Reduction; Sample Size; Scientist; Site; Smoker; Smoking; Smoking Cessation Intervention; Smoking Prevention; Smoking treatment; Stimulus; Testing; Tobacco Use Disorder; Tobacco use; Vulnerable Populations; Weight; Weight Gain; Woman; Work; alcohol effect; attenuation; cigarette smoke; cigarette smoking; dietary; disability; efficacy evaluation; emotional stimulus; exenatide; exercise program; improved; innovation; long term abstinence; mortality; nicotine patch; nicotine replacement; novel; novel strategies; obesity risk; placebo controlled study; pre-clinical; preclinical study; premature; primary outcome; randomized, clinical trials; 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 尽管在过去几十年中吸烟率有所下降，但目前仍有超过3400万美国人吸烟。 吸烟和烟草使用仍然是导致死亡、残疾和疾病的主要可预防原因。之间 戒烟后体重增加（PCWG）是常见的，并归因于吸烟者戒烟后体重增加。 在戒烟后的最初几周和几个月内的能量摄入。PCWG存在问题有三个原因。一是很多 吸烟者，特别是女性，报告说对PCWG的恐惧是戒烟的主要障碍。第二，PCWG可以沉淀 复发第三，PCWG可能导致慢性疾病的发作，如肥胖或2型糖尿病 糖尿病。一线治疗，即尼古丁替代疗法（NRT），伐尼克兰和安非他酮有助于 人们戒烟，但对PCWG没有临床意义的影响。我们最近的试点工作表明， 用胰高血糖素样肽-1受体（GLP-1 R）激动剂、缓释艾塞那肽 作为尼古丁贴片的辅助治疗，改善糖尿病前期和/或超重患者的戒断情况并降低PCWG 寻求治疗的吸烟者这些结果与GLP-1 R激动剂的临床前报告一致， 降低尼古丁和食物的奖励作用，支持GLP-1 R作为促进 戒烟和减少PCWG。拟议的研究将评估延长释放的疗效 艾塞那肽作为尼古丁贴片的辅助药物对戒烟和PCWG的作用 当大多数体重增加时，戒烟。一项双盲试验被提议，在该试验中，寻求治疗的吸烟者 将随机接受2 mg艾塞那肽（每周一次）或安慰剂作为尼古丁贴片的辅助治疗， 14周，从目标戒烟日前2周开始。主要结局指标为治疗结束时 戒烟（连续4周）和PCWG。我们预测，exenetamine将改善禁欲， 相对于安慰剂减轻PCWG。探索性目标将检查以下方面的长期（6个月）影响： 实验对主要研究结果的影响以及实验对食物神经情感反应的影响， 尼古丁相关刺激本研究的创新方面包括：1）靶向GLP-1 R以促进吸烟 停止和减少PCWG; 2）测试一种批准的药物，可以迅速部署， 与NRT联合使用的连续治疗; 3）为开展关键III期研究提供动力 确定艾塞那肽-NRT联合治疗疗效的临床试验和4）探索推定的机制 参与exenestrin对吸烟和PCWG的影响。该项目将为以下方面做出重大贡献 通过确定一种一流的辅助药物， 独特地针对戒烟和体重增加。此R 01重新提交申请是由早期- 阶段调查员已经组建了一个拥有相关专业知识和资源的科学家团队， 包括两个网站的招聘能力，以确保及时招生和顺利完成一个大的 样本量（N=216）。

项目成果

Exenatide as an adjunct to nicotine patch for smoking cessation and prevention of postcessation weight gain among treatment-seeking smokers with pre-diabetes and/or overweight: study protocol for a randomised, placebo-controlled clinical trial.

• DOI: 10.1136/bmjopen-2023-072707
• 发表时间: 2023-06-14
• 期刊: BMJ OPEN
• 影响因子: 2.9
• 作者: Yammine, Luba;Verrico, Christopher D.;Versace, Francesco;Webber, Heather E.;Suchting, Robert;Weaver, Michael F.;Kosten, Thomas R.;Alibhai, Husein;Cinciripini, Paul M.;Lane, Scott D.;Schmitz, Joy M.
• 通讯作者: Schmitz, Joy M.