Nicotinic Receptor Levels After Stopping Smoking

NCT01704573

Last updated date
Study Location
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Nicotine Addiction
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-65 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

1. Ages 18 to 65 years old.

2. Smoke 10 cigarettes per day for the previous 6 months.

3. Weigh less than 300lbs (due to limitations of the PET and MRI scanners).

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


1. Self-reported history of head trauma or brain (or CNS) tumor.


2. Self-reported history of claustrophobia (contraindicated for PET and MRI).


3. Having a cochlear implant or wearing bilateral hearing aids.


4. Self-reported use of pacemakers, certain metallic implants, or presence of metal
in the eye as contraindicated for MRI.


5. History of gunshot wound.


6. Circumstances or conditions that may interfere with magnetic resonance imaging
(MRI)


7. Inability to complete the baseline study procedures within four hours and/or
correctly, as determined by the PI.

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Nicotine AddictionNicotinic Receptor Levels After Stopping Smoking
NCT01704573
  1. Philadelphia, Pennsylvania
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title Nicotinic Receptor Levels After Stopping Smoking
Official Title Nicotinic Receptor Availability in Slow and Fast Nicotine Metabolizers
Brief Summary This positron emission tomography (PET) study examines the effects of 24 hours abstinence from smoking on return to availability of neuronal nicotinic receptors in slow and fast metabolizers of nicotine.
Detailed Description

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 ?4?2* nicotinic acetylcholine receptors (nAChRs) in the brain. The ?4?2* 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 ?4?2* nAChRs during early abstinence. The investigators will measure ?4?2* 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 ?4?2* 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 ?4?2* 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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Two saliva samples will be collected at the medical screening session. A 6ml saliva sample will be used for nicotine metabolite ratio (NMR) estimation, and a 2ml saliva sample for DNA extraction (using an Oragene collection kit).
Sampling Method Probability Sample
Study Population

20 adult, non-treatment seeking smokers, reporting consumption of greater than/equal to 10 cigarettes per day for at least 6 months will be the target population for the study. Participants will first be screened over the phone and then complete an in-person medical screen to ensure final eligibility. Enrolled participants will complete 2 PET scans and an MRI scan.

6 smokers who have completed the study and have agreed to be re-contacted for future studies will be invited to participate in an additional procedure. Participants will be screened over the phone and complete an in-person medical screen to ensure final eligibility. Enrolled participants will complete 1 PET scan.

Condition Nicotine Addiction
Intervention Drug: 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine

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
Study Groups/Cohorts 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 ?4?2* 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.

Intervention: Drug: 2-[18F]-fluro-3-[2(S)-2-azethidinylmethoxy]-pyridine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: October 9, 2012)
20
Original Actual Enrollment Same as current
Actual Study Completion Date December 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Ages 18 to 65 years old.
  2. Smoke 10 cigarettes per day for the previous 6 months.
  3. Weigh less than 300lbs (due to limitations of the PET and MRI scanners).

Exclusion Criteria:

  1. Smoking behavior:

    1. Current enrollment or plans to enroll in a smoking cessation program, or use other smoking cessation medications in the next 2 months.
    2. Provide a CO reading of less than 10 ppm at medical screening.
  2. Alcohol/Drugs:

    1. History of substance abuse and/or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants).
    2. Positive drug screen at any of the sessions (see page 8 for list of drugs and/or contra-indicated medications).
    3. Current alcohol consumption that exceeds 25 standard drinks/week.
    4. Providing a breath alcohol concentration (BrAC) reading of greater than or equal to 0.01 at any session.
  3. Medical:

    1. Women who are pregnant, planning a pregnancy, or lactating; all female subjects shall undergo a serum pregnancy test at the medical screening session and urine pregnancy tests at the two PET scans and MRI scan.
    2. Women of child-bearing age must agree in writing to use an approved method of contraception or agree to abstain from sexual intercourse
    3. History or current diagnosis of the following psychiatric diagnoses identified by the MINI (Mini International Neuropsychiatric Interview) such as psychosis, bipolar disorder, schizophrenia, major current depression, or any Axis 1 disorder
    4. Self-report of serious or unstable disease within the past 6 months (e.g., cancer [except melanoma], HIV/AIDS, stroke, angina, coronary disease, heart attack).
    5. History of epilepsy or a seizure disorder.
    6. Any medical or neurological condition that might interfere with the distribution of the radiotracer as determined by the study M.D.
  4. Medication:

    a. Current use or recent discontinuation (within last 14-days) of the following medications:

    • Any form of smoking cessation medication (Zyban, Wellbutrin, Wellbutrin SR, Chantix, NRT);
    • Recent (within last 14 days) or planned use of psychotropic medications (anti-psychotics, anti-depressants, anti-anxiety, anti-panic medications, mood stabilizers, opioids, and stimulants).
    • Participants shall be instructed to refrain from using any study prohibited drugs (note - participants are allowed to take prescription medicines not in the exclusion list) throughout their participation in the study.
  5. Imaging-Related Exclusion Criteria:

    1. Self-reported history of head trauma or brain (or CNS) tumor.
    2. Self-reported history of claustrophobia (contraindicated for PET and MRI).
    3. Having a cochlear implant or wearing bilateral hearing aids.
    4. Self-reported use of pacemakers, certain metallic implants, or presence of metal in the eye as contraindicated for MRI.
    5. History of gunshot wound.
    6. Circumstances or conditions that may interfere with magnetic resonance imaging (MRI)
    7. Inability to complete the baseline study procedures within four hours and/or correctly, as determined by the PI.
Sex/Gender
Sexes Eligible for Study:All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT01704573
Other Study ID Numbers 812051
P50CA143187 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD:No
Responsible Party University of Pennsylvania
Study Sponsor University of Pennsylvania
Collaborators
  • Pfizer
  • National Cancer Institute (NCI)
Investigators
Principal Investigator:Caryn Lerman, PhDUniversity of Pennsylvania
PRS Account University of Pennsylvania
Verification Date June 2017