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Medication development of a novel therapeutic for smoking cessation

新型戒烟疗法的药物开发

基本信息

批准号：
8914708
负责人：
DARLENE H BRUNZELL
金额：
$ 77.17万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-18 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8914708
关键词：
Abstinence Adverse effects Affect Alleles American Attenuated Behavior Control Behavioral Benefits and Risks Biological Brain Bupropion Cause of Death Clinical Clinical Research Clinical Trials Crossover Design Data Development Dose FDA approved Failure Feasibility Studies Food Future Genetic study Health Care Costs Human Impaired cognition Individual Industry Infusion procedures Knock-out Lead Measures Methods Motivation Mus Nicotine Nicotine Dependence Nicotinic Receptors Oral Pharmaceutical Preparations Phase Phase III Clinical Trials Placebo Effect Placebos Population Poverty Pre-Clinical Model Procedures Psychological reinforcement Public Health Randomized Clinical Trials Rattus Reporting Research Research Personnel Rewards Rodent Rodent Model Safety Sampling Schizophrenia Screening procedure Self Administration Self-Administered Smoker Smoking Societies Specificity Staging Symptoms Testing Therapeutic Tobacco Dependence Tobacco Use Cessation Treatment Efficacy Vulnerable Populations Withdrawal Work attenuation base cigarette smoking cost craving drug testing economic cost effective therapy efficacy testing experience innovation interest nicotine replacement novel novel therapeutics null mutation pre-clinical pre-clinical research preclinical efficacy preference receptor expression receptor function smoking cessation therapy design varenicline

项目摘要

DESCRIPTION (provided by applicant): Nearly 50 million Americans smoke cigarettes, the leading preventable cause of death worldwide. Although most report wanting to quit, few are successful during a given quit attempt even with currently available therapeutics. Of dozens of drugs tested in clinical trials for cessation over the last three decades, only 3 have been approved by the FDA (nicotine replacement, varenicline, bupropion). Additional effective medications are needed to help the majority of dependent smokers succeed in quitting permanently. This application uses a streamlined two-stage approach to evaluate the efficacy of a new compound as a medication for smoking cessation. In the first stage, preclinical feasibility studies will be performed based on highly convincing preliminary data in rodent models that are validated predictors of medications for smoking cessation in humans. These will be followed by the second stage, human clinical Phase 2a studies to detect medication evidence of efficacy for smoking cessation. Abstinence due to medication versus placebo will be compared within a well-validated, innovative procedure for initial test of efficacy. We will also assess the mechanisms through which this medication reverses symptoms of abstinence. These clinical studies benefit from a within- subject crossover design as a high throughput method for predicting therapeutic efficacy of smoking cessation drugs in a highly efficient manner. Moreover, a highly innovative component of this application is to test medication efficacy for smoking cessation in both the broader population of healthy dependent smokers and in smokers with schizophrenia, who have very high rates of smoking but limited therapeutic alternatives to quit smoking. The feasibility of this research is substantial, given the investigators' extensive experience conducting very similar preclinical and clinical research. Results of this application could lead to a new medication to treat nicotine dependence, reducing enormous costs to public health and providing perhaps the first effective treatment for cessation in the most vulnerable smokers.

描述（由申请人提供）：近5000万美国人吸烟，这是全球可预防的主要死亡原因。虽然大多数人报告想要戒烟，但即使使用目前可用的治疗方法，也很少有人在给定的戒烟尝试中成功。在过去的三十年里，在数十种用于戒烟的临床试验药物中，只有3种获得了FDA的批准（尼古丁替代品，伐尼克兰，安非他酮）。需要额外的有效药物来帮助大多数依赖性吸烟者成功永久戒烟。本申请使用简化的两阶段方法来评估一种新化合物作为戒烟药物的疗效。在第一阶段，将基于啮齿动物模型中高度令人信服的初步数据进行临床前可行性研究，这些数据是人类戒烟药物的有效预测因子。随后将进行第二阶段，人类临床2a期研究，以检测戒烟疗效的药物证据。将在经过充分验证的创新程序中比较药物与安慰剂引起的戒断，以进行初步疗效检验。我们还将评估这种药物逆转禁欲症状的机制。这些临床研究受益于受试者内交叉设计，作为以高效方式预测戒烟药物治疗效果的高通量方法。此外，本申请的一个高度创新的组成部分是在更广泛的健康依赖性吸烟者人群和患有精神分裂症的吸烟者中测试戒烟的药物疗效，这些吸烟者的吸烟率非常高，但戒烟的治疗替代方案有限。考虑到研究者在进行非常相似的临床前和临床研究方面的丰富经验，本研究的可行性是巨大的。这一应用的结果可能会导致一种新的药物来治疗尼古丁依赖，减少公共卫生的巨大成本，并可能为最脆弱的吸烟者提供第一种有效的戒烟治疗。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Initial Cross-Over Test of A Positive Allosteric Modulator of Alpha-7 Nicotinic Receptors to Aid Cessation in Smokers With Or Without Schizophrenia.

α-7 烟碱受体正变构调节剂的初步交叉测试有助于患有或不患有精神分裂症的吸烟者戒烟。

DOI：
10.1038/npp.2017.292
发表时间：
2018
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
0
作者：
Perkins,KennethA;RoyChengappa,KN;Karelitz,JoshuaL;Boldry,MargaretC;Michael,Valerie;Herb,Taylor;Gannon,Jessica;Brar,Jaspreet;Ford,Lisa;Rassnick,Stefanie;Brunzell,DarleneH
通讯作者：
Brunzell,DarleneH

Improving efficiency of initial tests for efficacy in smoking cessation drug discovery.

提高戒烟药物发现效果的初始测试效率。