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

Primary Purpose

Nicotine Dependence, Smoking Cue Reactivity, Relapse to Smoking

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

[11C]-PHNO

About this trial

This is an interventional basic science trial for Nicotine Dependence

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Healthy Smokers

Healthy Nonsmokers

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers

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

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.

Full Information

NCT ID

NCT01784016

First Posted

January 30, 2013

Last Updated

May 22, 2014

Sponsor

Mclean Hospital

Collaborators

National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT01784016

Brief Title

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

2. Study Status

Record Verification Date

May 2014

Overall Recruitment Status

Withdrawn

Why Stopped

Technical complications.

Study Start Date

January 2014 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mclean Hospital

Collaborators

National Institute on Drug Abuse (NIDA)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nicotine Dependence, Smoking Cue Reactivity, Relapse to Smoking

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Healthy Smokers

Arm Type

Experimental

Arm Description

Arm Title

Healthy Nonsmokers

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

[11C]-PHNO

Other Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers

Description

Time Frame

March 2014

Secondary Outcome Measure Information:

Title

Smoking Cue fMRI Reactivity Association with Dopamine D3 Receptor Binding Potential

Description

Time Frame

March 2014

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marc J. Kaufman, Ph.D.

Organizational Affiliation

Mclean Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

McLean Hospital

City

Belmont

State/Province

Massachusetts

ZIP/Postal Code

02478

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

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

City

Charlestown

State/Province

Massachusetts

ZIP/Postal Code

02129

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

20172508

Citation

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.

Results Reference

background

PubMed Identifier

12494400

Citation

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.

Results Reference

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PubMed Identifier

20599188

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.

Results Reference

background

PubMed Identifier

20600980

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.

Results Reference

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PubMed Identifier

15943487

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.

Results Reference

background

PubMed Identifier

16942635

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.

Results Reference

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

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