Brain Nicotine Receptor Density & Response to Nicotine Patch

脑尼古丁受体密度

• 批准号: 8557167
• 负责人: Arthur Brody
• 金额: $ 3.8万
• 依托单位: BRENTWOOD BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8557167
• 关键词: Abstinence; Adult; Advertisements; Affect; Aftercare; American; Binding; Bolus Infusion; Brain; Brain Stem; Brain imaging; Bupropion HCl; Carbon Monoxide; Cerebellum; Chantix; Cigarette; Cigarette Smoker; Clinical; Clinical Data; Continuous Infusion; Cotinine; Data; Exhalation; Goals; Group Psychotherapy; Health; Human; Image; Inhalators; Internet; Lead; Link; Magnetic Resonance Imaging; Measures; Mental Depression; Methods; Newspapers; Nicotine; Nicotine Dependence; Nicotinic Receptors; Nose; Outcome; Participant; Patient Preferences; Patients; Persons; Pharmaceutical Preparations; Placebos; Positron-Emission Tomography; Procedures; Publishing; Randomized; Receptor Up-Regulation; Recruitment Activity; Reporting; Research; Risk; Satiation; Scanning; Self Efficacy; Severities; Smoke; Smoker; Smoking; Smoking Status; Telephone; Thalamic structure; Time; TimeLine; Tobacco; Tobacco Dependence; Treatment outcome; Up-Regulation; Visit; Withholding Treatment; Zyban; base; brain tissue; cigarette smoking; cost; craving; density; effective therapy; follow-up; imaging modality; improved; interest; neuropsychiatry; nicotine patch; nicotine replacement; non-smoker; non-smoking; pyridine; radiotracer; receptor; receptor density; response; screening; smoking cessation; smoking prevalence; standard of care; urinary; varenicline

DESCRIPTION (provided by applicant): Even though the health risks and societal costs of cigarette smoking are well-known, roughly 19.8% of American adults continue to smoke. While most smokers endorse a desire to quit, very few (< 5%) will actually quit in a given year without treatment, and only about 20-25% achieve abstinence after 6 months or more of effective treatment. Therefore, there continues to be a vital need to improve outcomes for cigarette smokers seeking treatment. Current first-line medications for Tobacco Dependence include nicotine replacement therapies (such as the patch, gum, lozenge, nasal spray, and inhaler), varenicline HCl (Chantix), and bupropion HCl (Zyban), with the current standard of care in most treatment settings being to choose specific medications based primarily on availability, ease of use, and patient preference. The goal of the proposed research is to improve the delivery of smoking cessation treatment by determining if pre-treatment 1422* nicotinic acetylcholine receptor (nAChR) density in cigarette smokers is associated with smoking cessation outcome with the standard nicotine patch taper. Pilot data from our ongoing studies using positron emission tomography (PET) and the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (abbreviated as 2-FA) in cigarette smokers indicate that the severity of up-regulation of 1422* nAChRs predicts who will be more or less likely to respond to treatment with the nicotine patch, and that this relationship between 1422* nAChR up-regulation and treatment outcome is more specific for nicotine patch treatment than for other smoking cessation treatments which are not linked as clearly with 1422* nAChR occupancy (e.g., bupropion HCl and group psychotherapy). The proposed study builds upon several ongoing lines of research. First, the 2-FA PET method to be used here was recently developed and refined by our group and close collaborators, and these refinements allow for improved precision in determining brain 1422* nAChR density in smokers than was previously possible. Second, both functional brain imaging studies of humans and post-mortem studies of human brain tissue demonstrate up-regulation of 1422* nAChRs in cigarette smokers compared to non-smoking controls, and the pilot data for this study indicates that the severity of this up-regulation is associated with response to nicotine replacement therapy. Third, the nicotine patch taper continues to be widely used. And fourth, clinical features and general measures of brain function (e.g., brain activity) have been used to predict treatment outcomes in Tobacco Dependence and other neuropsychiatric conditions; however, to our knowledge, there are no published reports linking the density of a specific brain receptor (1422* nAChRs) with treatment outcome for a medication that affects that receptor. For the proposed study, tobacco dependent cigarette smokers (n = 148; 10 to 30 cigarettes per day) will be recruited through newspaper and internet advertisements. Participants will undergo telephone and in-person screening, followed within one week by a 2-FA PET scanning session. For this PET session, a bolus of 2-FA will be injected over 1 minute and 2-FA will be infused for the remainder of the session. After 3 h (the amount of time needed for the radiotracer to reach an approximate steady state in the brain), participants will undergo 1 h of PET scanning. They will then be taken out of the scanner and will smoke to satiety (2 to 3 cigarettes). Participants will then be scanned an additional 3.5 h, so that both specific and non-displaceable 2-FA binding can be determined in regions of interest (ROIs) (e.g., thalamus, brainstem, and cerebellum). A structural magnetic resonance image of the brain will be obtained within one week of the PET session to aid in localization of ROIs on PET. Participants will then be randomly assigned to a 10-week course of treatment with either an active nicotine or matching placebo patch taper. Smoking status will be assessed at each weekly treatment visit and at the end of treatment using participant reports, exhaled carbon monoxide levels, and urinary cotinine levels. Pre-treatment 1422* nAChR density in the ROIs will be linked with treatment outcome (e.g., quit status) and other variables for the treatment groups (nicotine and placebo patch) separately and for the total group. Additionally, we will explore whether the combination of information from the PET images and rating scales can be used to identify even more robustly who will quit smoking with nicotine patch treatment.

描述(申请人提供)：尽管吸烟的健康风险和社会代价是众所周知的，但大约19.8%的美国成年人继续吸烟。虽然大多数吸烟者支持戒烟的愿望，但很少(5%)的人实际上会在没有接受治疗的情况下在一年内戒烟，只有大约20%-25%的人在经过6个月或更长时间的有效治疗后实现戒烟。因此，仍然迫切需要改善寻求治疗的吸烟者的结果。目前治疗烟草依赖的一线药物包括尼古丁替代疗法(如贴片、口香糖、含片、鼻喷雾和吸入器)、盐酸伐伦克林(Chantix)和盐酸安非他酮(Zyban)，目前大多数治疗环境中的护理标准是主要根据可用性、易用性和患者偏好选择特定药物。这项拟议研究的目的是通过确定吸烟者的1422*烟碱乙酰胆碱受体(NAChR)密度是否与标准尼古丁贴片缩减的戒烟结果相关，来改善戒烟治疗的提供。我们正在进行的利用正电子发射断层扫描(PET)和放射性示踪剂2-[18F]氟-3-(2(S)氮乙基甲氧基)吡啶(简称2-FA)在吸烟者中进行的研究的试点数据表明，1422*nAChRs上调的严重程度可以预测谁将或多或少对尼古丁贴片的治疗有反应，而且这种1422*nAChR上调与治疗结果之间的关系在尼古丁贴片治疗中更为具体，而其他戒烟治疗(如盐酸安非他酮和集体心理治疗)与1422*nAChR的占有率没有那么明显的联系。拟议的研究建立在几个正在进行的研究的基础上。首先，将在这里使用的2-FA PET方法是我们团队和密切合作者最近开发和改进的，这些改进允许比以前更精确地确定吸烟者的大脑1422*nAChR密度。其次，对人类的脑功能成像研究和对人脑组织的尸检研究都表明，与不吸烟的对照组相比，吸烟者的1422*nAChRs上调，这项研究的试点数据表明，这种上调的严重程度与尼古丁替代疗法的反应有关。第三，尼古丁贴片继续广泛使用。第四，临床特征和大脑功能的一般测量(例如，大脑活动)已被用于预测烟草依赖和其他神经精神疾病的治疗结果；然而，据我们所知，没有发表报告将特定大脑受体的密度(1422*nAChRs)与影响该受体的药物的治疗结果联系起来。在拟议的研究中，将通过报纸和互联网广告招募依赖烟草的吸烟者(n=148；每天10至30支香烟)。参与者将接受电话和面对面的筛查，然后在一周内进行2-FA PET扫描。对于这次PET治疗，将在1分钟内注射一剂2-FA，并在接下来的治疗中注入2-FA。3小时后(放射性示踪剂在大脑中达到接近稳定状态所需的时间)，参与者将接受1小时的正电子发射计算机断层扫描。然后，它们将被从扫描仪中取出，并将吸烟至饱腹感(2至3支)。然后将对参与者进行额外的3.5小时扫描，以便可以确定感兴趣区域(ROI)(例如丘脑、脑干和小脑)的特异性和不可移位的2-FA结合。脑部的结构磁共振图像将在PET会议的一周内获得，以帮助在PET上定位ROI。然后，参与者将被随机分配到为期10周的疗程中，使用活性尼古丁或匹配的安慰剂贴片逐渐减少治疗。吸烟状况将在每周治疗访问和治疗结束时使用参与者报告、呼出的一氧化碳水平和尿可替宁水平进行评估。治疗前ROI中的1422*nAChR密度将分别与治疗结果(例如，戒烟状态)和治疗组(尼古丁和安慰剂贴片)的其他变量联系在一起。此外，我们将探索PET图像和评级量表的信息组合是否可以用来更有力地识别谁将通过尼古丁贴片治疗戒烟。

项目成果

Quantitative Molecular Imaging of Neuronal Nicotinic Acetylcholine Receptors in the Human Brain with A-85380 Radiotracers.

使用 A-85380 放射性示踪剂对人脑神经元烟碱乙酰胆碱受体进行定量分子成像。

• DOI: 10.2174/157340511795445676
• 发表时间: 2011
• 期刊: Current medical imaging reviews
• 作者: Lotfipour,Shahrdad;Mandelkern,Mark;Brody,ArthurL
• 通讯作者: Brody,ArthurL

VIRTUAL REALITY CUE EXPOSURE THERAPY FOR THE TREATMENT OF TOBACCO DEPENDENCE.

• 发表时间: 2012
• 期刊: Journal of cyber therapy and rehabilitation
• 作者: C. Culbertson;Stephanie Shulenberger;R. De La Garza;T. Newton;A. Brody

Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans.

• DOI: 10.1016/j.neuropharm.2013.02.015
• 发表时间: 2014-09
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Jasinska AJ;Zorick T;Brody AL;Stein EA
• 通讯作者: Stein EA

Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers.

• DOI: 10.1017/s1461145712001022
• 发表时间: 2013-06
• 期刊: The international journal of neuropsychopharmacology
• 作者: Brody AL;Mukhin AG;La Charite J;Ta K;Farahi J;Sugar CA;Mamoun MS;Vellios E;Archie M;Kozman M;Phuong J;Arlorio F;Mandelkern MA
• 通讯作者: Mandelkern MA

In vivo brain imaging of human exposure to nicotine and tobacco.

• DOI: 10.1007/978-3-540-69248-5_6
• 发表时间: 2009
• 期刊: Handbook of experimental pharmacology
• 作者: Sharma A;Brody AL
• 通讯作者: Brody AL