Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers

NCT ID: NCT01784016

Last Updated: 2014-05-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2014-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Nicotine Dependence Smoking Cue Reactivity Relapse to Smoking

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

[11C]-PHNO

Intervention Type RADIATION

\[11C\]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.

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.

Group Type EXPERIMENTAL

[11C]-PHNO

Intervention Type RADIATION

\[11C\]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.

Interventions

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[11C]-PHNO

\[11C\]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.

Intervention Type RADIATION

Other Intervention Names

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11C-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

Mclean Hospital

OTHER

Sponsor Role lead

Responsible Party

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Marc J. Kaufman

Director, Translational Imaging Laboratory, McLean Hospital

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marc J. Kaufman, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Mclean Hospital

Locations

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McLean Hospital

Belmont, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging

Charlestown, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 20172508 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12494400 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20599188 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20600980 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15943487 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16942635 (View on PubMed)

Other Identifiers

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R21DA031925-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

SmokingPETD2-3fMRI

Identifier Type: -

Identifier Source: org_study_id

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