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

This study has been withdrawn prior to enrollment.
(Technical complications.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01784016
First Posted: February 5, 2013
Last Update Posted: May 23, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Marc J. Kaufman, Mclean Hospital
  Purpose

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.


Condition Intervention Phase
Nicotine Dependence Smoking Cue Reactivity Relapse to Smoking Radiation: [11C]-PHNO Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers

Resource links provided by NLM:


Further study details as provided by Marc J. Kaufman, Mclean Hospital:

Primary Outcome Measures:
  • Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers [ Time Frame: March 2014 ]
    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.


Secondary Outcome Measures:
  • Smoking Cue fMRI Reactivity Association with Dopamine D3 Receptor Binding Potential [ Time Frame: March 2014 ]
    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.


Enrollment: 0
Study Start Date: January 2014
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Radiation: [11C]-PHNO
[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.
Other Name: 11C-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol
Experimental: 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.
Radiation: [11C]-PHNO
[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.
Other Name: 11C-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01784016


Locations
United States, Massachusetts
McLean Hospital
Belmont, Massachusetts, United States, 02478
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging
Charlestown, Massachusetts, United States, 02129
Sponsors and Collaborators
Mclean Hospital
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Marc J. Kaufman, Ph.D. Mclean Hospital
  More Information

Publications:
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.
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.
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.
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. Epub 2006 Aug 31.

Responsible Party: Marc J. Kaufman, Director, Translational Imaging Laboratory, McLean Hospital, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01784016     History of Changes
Other Study ID Numbers: SmokingPETD2-3fMRI
R21DA031925-01A1 ( U.S. NIH Grant/Contract )
First Submitted: January 30, 2013
First Posted: February 5, 2013
Last Update Posted: May 23, 2014
Last Verified: May 2014

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders


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