Nicotinic Receptor Levels After Stopping Smoking
|ClinicalTrials.gov Identifier: NCT01704573|
Recruitment Status : Completed
First Posted : October 11, 2012
Last Update Posted : June 16, 2017
|Condition or disease||Intervention/treatment|
|Nicotine Addiction||Drug: 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine|
The nicotine metabolite ratio (NMR), a stable marker of nicotine clearance rate, is a robust predictor of smoking relapse. Individuals who are fast nicotine metabolizers have higher rates of relapse, compared to slow metabolizers, on nicotine replacement or placebo treatment. Nicotine exerts its reinforcing properties, in part, by binding to α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The α4β2* nAChRs are abundant and have high affinity for nicotine relative to other nAChR subtypes. The goal of this project is to identify abstinence-induced changes in neuronal nicotinic receptor availability that may underlie risk for smoking relapse.
The investigators propose to utilize positron emission tomography (PET) imaging to examine the association of variation in nicotine metabolism with return to availability of α4β2* nAChRs during early abstinence. The investigators will measure α4β2* receptor availability using the PET radio-ligand 2-[18F]FA, administered with bolus injection, on two separate occasions: during smoking as usual and after 24 hours of abstinence. The proposed study will help us understand the neurochemical mechanisms that underlie the higher risk of relapse among faster nicotine metabolizers, thereby pointing to potential targets for tailored therapy for these smokers at increased risk.
In addition, the investigators will invite six subjects who have completed the two PET scans described above to complete a third PET scan. During this third PET scan, the investigators plan to measure α4β2* receptor availability using the PET radio-ligand 2-[18F]FA, administered as bolus plus constant infusion after 24 hours of abstinence. The purpose will be to compare α4β2* nAChR binding potential data from the bolus 2-[18F]FA infusion protocol used in the main study to the bolus plus constant infusion protocol used in this third PET scan.
The protocol of this third PET scan will help the investigators demonstrate the feasibility at the University of Pennsylvania of administering the radiotracer as a bolus plus constant infusion, and the feasibility of scanning for two hours (versus one hour in the current protocol) paradigm. This data is important pilot data for future NIH grant submissions using this radiotracer.
|Study Type :||Observational|
|Actual Enrollment :||20 participants|
|Official Title:||Nicotinic Receptor Availability in Slow and Fast Nicotine Metabolizers|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||March 2012|
|Actual Study Completion Date :||December 2012|
NMR by abstinence status
This study uses a mixed design with one between-subject factor (NMR: continuous variable) and one within-subject factor (session: 24 hours abstinent vs. smoking as usual) to examine NMR by abstinence status interactions on α4β2* nAChR availability using 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine (2-[18F]FA) PET imaging.
Subjects will participate in two one-hour PET sessions: a) after smoking as usual (smoking exposure standardized) and b) the other following 24 hours of smoking abstinence.
All participants who complete both PET scans will also complete an anatomical MRI scan.
The study will be performed using an Investigational New Drug (IND) Application for the 2-[18F]FA radioligand. The 2-[18F]FA radiotracer allows us to measure nicotine receptors. The PET imaging technique used at these sessions allows us to measure the amount of light that 2-[18F]FA gives off in different regions of the brain, we can estimate how many nicotine receptors are in that region.
2-[18F]FA (radiotracer) is investigational, which means it is not approved by the United States Food and Drug Administration (FDA) for the way that it is being used in this research study. For this reason, we have received approval for all procedures in the current study including the use of 2-[18F]FA from the FDA.
Other Name: 2-[18F]FA, 2-FA
- Change in α4β2* nAChR binding potential [ Time Frame: Week 1 and up to Week 5 ]
This study uses a mixed design. A within-subject positron emission tomography (PET) study comparing α4β2* nAChR availability, using 2-[18F]FA PET imaging, at two timepoints (1) during smoking as usual; and (2) after 24 hours of overnight abstinence. The order of the PET scans will be counterbalanced across subjects to prevent order effects that could bias the study results. Nicotine metabolite ratio (NMR) serves as the between-subject factor.
The minimum amount of time between scans will be separated by one week. The maximum amount of time allowable between scans will be 4 weeks.
- Cigarette craving [ Time Frame: Week 0, Week 1, and up to Week 5 ]
The 10-item brief QSU (QSU-B) questionnaire will be used to assess smoking urges at medical screening and at each PET scanning session. The QSU contains 2 subscales (anticipation of reward, relief from negative affect).
During each PET scanning session, the measure will be administered both before and after the PET scan.
- Behavioral Performance on cognitive tasks [ Time Frame: Week 1 and up to Week 5 ]Explore potential correlations between α4β2* nAChR availability (smoking versus abstinence) with cognitive performance using 3 computer tasks: an N-back task assessing working memory, a continuous performance task assessing sustained attention, and a task assessing attentional bias to smoking cues.
Biospecimen Retention: Samples With DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01704573
|United States, Pennsylvania|
|Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Caryn Lerman, PhD||University of Pennsylvania|