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