- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT01784016
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.
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
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Massachusetts
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Belmont, Massachusetts, Estados Unidos, 02478
- McLean Hospital
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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Charlestown, Massachusetts, Estados Unidos, 02129
- Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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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.
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[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.
Otros nombres:
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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.
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[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Smoking Cue fMRI Reactivity Association with Dopamine D3 Receptor Binding Potential
Periodo de tiempo: 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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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Marc J. Kaufman, Ph.D., McLean Hospital
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- SmokingPETD2-3fMRI
- R21DA031925-01A1 (Subvención/contrato del NIH de EE. UU.)
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