Clinical trial NCT01784016: Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers
Official title: Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Nicotine Dependence
Smoking Cue Reactivity
Relapse to Smoking
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2013-02-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers
timeFrame: March 2014
Secondary outcomes:
measure: Smoking Cue fMRI Reactivity Association with Dopamine D3 Receptor Binding Potential
timeFrame: March 2014
Other outcomes:
Locations:
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Charlestown
country: United States
facility: Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging
state: Massachusetts
Study officials:
affiliation: Mclean Hospital
name: Marc J. Kaufman, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
citation: 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.
citation: 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.