Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans
2013年3月4日 更新者：Bernard Le Foll、Centre for Addiction and Mental Health
Does the Insula Control Smoking-induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans. Part I: Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans.
This study will evaluate effects of smoking on the dopaminergic system by using PET tomography with new radioligand, [11C]-(+)-PHNO.
Our primary hypothesis is that smoking a cigarette will produce dopamine release and this release can be measured using PET imaging and the [11C]-(+)-PHNO radiotracer.
The secondary hypothesis is that this smoking induced dopamine release will be correlated with subjective craving and anxiety ratings.
研究概览
地位
完全的
条件
详细说明
This will be a within-subjects study in healthy male and female smokers.
There will be one within factor condition: Smoking and Non Smoking.
Therefore, there will be a repeated measure of PET scans using [11C]-(+)-PHNO under two different conditions.
Ten subjects (n=5 male and n=5 female) included in the study will come on two different days and will have a Smoking or Non smoking session performed just before the PET study.
Subjective assessments will be conducted at each experimental condition.
研究类型
观察性的
注册 (实际的)
10
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
-
Ontario
-
Toronto、Ontario、加拿大、M5S 2S1
- Centre for Addiction and Mental Health - 33 Russell St
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
21年 至 45年 (成人)
接受健康志愿者
不
有资格学习的性别
全部
取样方法
非概率样本
研究人群
Healthy smokers
描述
Inclusion Criteria:
- Adult males or females
- Regular smoking of at least 10 cigarettes, excluding ultra-low nicotine cigarettes, per day for at least two years
- Score on the Fagerstrom Test for Nicotine Dependence of 4 or more
- No intention to quit or reduce tobacco use, and no treatment for tobacco dependence currently
- No history of abuse of or dependence on any other drug, defined by DSM-IV criteria
Exclusion Criteria:
- Pregnancy
- Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning
- Claustrophobia
- Cardiovascular or cerebrovascular diseases
- Major psychiatric disorders including mood, anxiety or psychotic disorders
- History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor
- Gross structural brain abnormalities as revealed by T1 weighted images
- Current use or use during the previous month of medication that may affect the CNS (e.g. neuroleptics, bupropion)
- Learning disability, amnesia or other conditions that impede memory and attention
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
|---|
|
Healthy smokers
Healthy male and female smokers.
Each subject will undergo PET scan (along with craving and anxiety questionnaires) on two conditions - Smoking and Non-smoking - on two separate visits.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
[11C]-(+)-PHNO binding potential
大体时间：Up to 14 days between PET scans
|
The process of imaging requires the injection of a positron-emitting radiotracer (here, [11C]-(+)-PHNO) that binds to the protein of interest (here, dopamine receptor DRD2/3) followed by the measurement of this binding using the PET scanner.
Dopamine release increases DRD 2/3 occcupancy which results in decreased radiotracer's binding potential, and vice versa.
[11C]-(+)-PHNO binding potential will be measured on two different conditions (Smoking vs. Non-smoking) on two separate days.
|
Up to 14 days between PET scans
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Subjective reports of craving
大体时间：Up to 14 days between PET scans
|
Levels of subjective craving will be assessed prior to and after each condition (Smoking vs. Non-smoking) on two separate days.
Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire of Smoking Urges, The Urge to Smoke scale, Tobacco Craving Questionnaire, and 21-item Visual Analogue Scale will be used.
|
Up to 14 days between PET scans
|
|
Subjective reports of anxiety
大体时间：Up to 14 days between PET scans
|
Subjective reports of anxiety will be collected prior to and after each condition (Smoking vs. Non-smoking) on two separate days.
State anxiety questions from the Spielberg State-Trait Anxiety Inventory will be used.
|
Up to 14 days between PET scans
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
调查人员
- 首席研究员：Bernard Le Foll, MD、Centre for Addiction and Mental Health
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Brody AL, Olmstead RE, London ED, Farahi J, Meyer JH, Grossman P, Lee GS, Huang J, Hahn EL, Mandelkern MA. Smoking-induced ventral striatum dopamine release. Am J Psychiatry. 2004 Jul;161(7):1211-8. doi: 10.1176/appi.ajp.161.7.1211.
- Wilson AA, McCormick P, Kapur S, Willeit M, Garcia A, Hussey D, Houle S, Seeman P, Ginovart N. Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography. J Med Chem. 2005 Jun 16;48(12):4153-60. doi: 10.1021/jm050155n.
- Le Foll B, Goldberg SR, Sokoloff P. The dopamine D3 receptor and drug dependence: effects on reward or beyond? Neuropharmacology. 2005 Sep;49(4):525-41. doi: 10.1016/j.neuropharm.2005.04.022.
- Le Foll B, Schwartz JC, Sokoloff P. Dopamine D3 receptor agents as potential new medications for drug addiction. Eur Psychiatry. 2000 Mar;15(2):140-6. doi: 10.1016/s0924-9338(00)00219-4.
- Le Foll B, Goldberg SR, Sokoloff P. Dopamine D3 receptor ligands for the treatment of tobacco dependence. Expert Opin Investig Drugs. 2007 Jan;16(1):45-57. doi: 10.1517/13543784.16.1.45.
- Brody AL, Mandelkern MA, Olmstead RE, Scheibal D, Hahn E, Shiraga S, Zamora-Paja E, Farahi J, Saxena S, London ED, McCracken JT. Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. Arch Gen Psychiatry. 2006 Jul;63(7):808-16. doi: 10.1001/archpsyc.63.7.808.
- Boileau I, Guttman M, Rusjan P, Adams JR, Houle S, Tong J, Hornykiewicz O, Furukawa Y, Wilson AA, Kapur S, Kish SJ. Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-(+)-PHNO in drug-naive Parkinson's disease. Brain. 2009 May;132(Pt 5):1366-75. doi: 10.1093/brain/awn337. Epub 2009 Jan 19.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2011年2月1日
初级完成 (实际的)
2013年2月1日
研究完成 (实际的)
2013年3月1日
研究注册日期
首次提交
2011年2月22日
首先提交符合 QC 标准的
2011年2月22日
首次发布 (估计)
2011年2月24日
研究记录更新
最后更新发布 (估计)
2013年3月5日
上次提交的符合 QC 标准的更新
2013年3月4日
最后验证
2013年3月1日
更多信息
与本研究相关的术语
其他研究编号
- 143/2010
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.