Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers
This trial aims to determine whether dopamine D3 receptors are elevated in smokers versus nonsmokers and whether correlations exist between D3 receptor binding potential (BP) and functional MRI (fMRI) reactivity to smoking cues, which has been associated with smoking relapse vulnerability.
Neuroimaging measures of D3 BP and smoking cue fMRI reactivity will be collected concurrently in otherwise healthy nicotine-dependent smokers and age-matched nonsmokers using a 3 Tesla MRI scanner configured to conduct fMRI and Positron Emission Tomography (PET).
We will measure D3 receptor BP using radiolabeled [11C]-(+)-PHNO, which has a relatively higher affinity for D3 versus D2 receptors.
We hypothesize that D3 BP will be elevated in smokers versus nonsmokers and that in smokers, there will be a positive correlation between smoking cue fMRI reactivity and D3 BP.
研究概览
研究类型
阶段
- 阶段1
联系人和位置
学习地点
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Massachusetts
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Belmont、Massachusetts、美国、02478
- Mclean Hospital
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Boston、Massachusetts、美国、02114
- Massachusetts General Hospital
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Charlestown、Massachusetts、美国、02129
- Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- competent to provide written informed consent
- Smokers: self-report of smoking 15 or more cigarettes/day for the past year, self-report of smoking first cigarette of the day within 30 minutes of awakening, meets DSM-IV criteria for Nicotine Dependence, provides expired breath carbon monoxide reading of > 10 ppm at enrollment
- Nonsmokers: self-report of consuming <100 cigarettes in their lifetime, none in the last 6 months, provides expired breath carbon monoxide reading of < 9 ppm at enrollment
- Women of childbearing potential: negative STAT serum beta-human chorionic gonadotrophin pregnancy test before scanning
Exclusion Criteria:
- pregnant or able to become pregnant and not willing to undergo blood pregnancy test
- unstable medical illness with likely hospitalization for treatment within 6 months
- life-threatening arrhythmia, cerebro-vascular or cardiovascular event within 6 months of enrollment; liver function tests elevated over 2.5x normal; CNS tumor or seizure disorder
- users of other tobacco- or nicotine-containing products (gum, patches, e-cigarettes)
- lifetime history of DSM-IV bulimia, organic mental disorder, brain injury or psychotic disorder
- 6 month history of non-nicotine substance use disorder or major depression
- history of multiple adverse drug reactions
- current use of excluded concomitant medications (smoking cessation medications)
- known history of allergic reaction to the PET ligand [11C]-PHNO, its components, or any medication
学习计划
研究是如何设计的?
设计细节
- 主要用途:基础科学
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Healthy Smokers
Healthy smokers aged 18-50 years reporting average cigarette consumption of 15 or more cigarettes/day for the past year, providing an expired breath carbon monoxide reading exceeding 10 ppm at screening.
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[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.
其他名称:
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实验性的:Healthy Nonsmokers
Healthy nonsmoking controls aged 18-50 reporting consumption of <100 cigarettes in their lifetime, none in the last 6 months, providing an exhaled breath carbon monoxide reading of < 9 ppm at screening.
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[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.
其他名称:
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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 |
|---|---|---|
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Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers
大体时间:March 2014
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We will determine whether dopamine D3 receptor binding potential, a dimensionless number which represents the relative concentration of dopamine D3 receptors available for binding, is elevated in smokers versus nonsmoking controls.
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March 2014
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Smoking Cue fMRI Reactivity Association with Dopamine D3 Receptor Binding Potential
大体时间:March 2014
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In smokers, we will determine whether an association exists between smoking cue fMRI reactivity intensity (beta weight) and dopamine D3 receptor binding potential, a relationship between receptor (D3) density and dopamine occupancy.
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March 2014
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合作者和调查者
调查人员
- 首席研究员:Marc J. Kaufman, Ph.D.、Mclean Hospital
出版物和有用的链接
一般刊物
- 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.
- Janes AC, Pizzagalli DA, Richardt S, deB Frederick B, Chuzi S, Pachas G, Culhane MA, Holmes AJ, Fava M, Evins AE, Kaufman MJ. Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence. Biol Psychiatry. 2010 Apr 15;67(8):722-9. doi: 10.1016/j.biopsych.2009.12.034. Epub 2010 Feb 20. Erratum In: Biol Psychiatry. 2010 May 15;67(10):1002.
- Le Foll B, Diaz J, Sokoloff P. Increased dopamine D3 receptor expression accompanying behavioral sensitization to nicotine in rats. Synapse. 2003 Mar;47(3):176-83. doi: 10.1002/syn.10170.
- Searle G, Beaver JD, Comley RA, Bani M, Tziortzi A, Slifstein M, Mugnaini M, Griffante C, Wilson AA, Merlo-Pich E, Houle S, Gunn R, Rabiner EA, Laruelle M. Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11C]PHNO, and a selective D3 receptor antagonist. Biol Psychiatry. 2010 Aug 15;68(4):392-9. doi: 10.1016/j.biopsych.2010.04.038.
- Tziortzi AC, Searle GE, Tzimopoulou S, Salinas C, Beaver JD, Jenkinson M, Laruelle M, Rabiner EA, Gunn RN. Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy. Neuroimage. 2011 Jan 1;54(1):264-77. doi: 10.1016/j.neuroimage.2010.06.044. Epub 2010 Jun 30.
- Pak AC, Ashby CR Jr, Heidbreder CA, Pilla M, Gilbert J, Xi ZX, Gardner EL. The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions. Int J Neuropsychopharmacol. 2006 Oct;9(5):585-602. doi: 10.1017/S1461145706006560. Epub 2006 Aug 31.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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