Nicotine Addiction, Smoking Cessation
Conditions
Keywords
positron emission tomography, nicotine receptor
Brief summary
The investigators propose to use positron emission tomography (PET) imaging to determine whether nicotinic receptor availability at pretreatment predicts smoking cessation success. The investigators will recruit 30 smokers from those enrolled in the Pharmacogenetics of Nicotine Addiction Treatment clinical trial. The investigators will measure nicotinic receptor availability using the PET radioligand 2-\[18F\]FA, after overnight abstinence and prior to initiation of treatment.
Detailed description
Subjects will be asked to complete a short screening session, an orientation phone call, and two imaging sessions: one PET imaging session and one MRI session. Intake Session. This session will familiarize subjects with the study procedures and risks, as well as determine initial eligibility for the study. Subjects will first complete an Imaging Screening Form with study personnel. Subjects will also complete a Magnet Safety Form to check for any metal in the body. Finally, subjects will complete a Scanning Registration Form. Orientation Call. Dr. Dubroff (the Principal Investigator and study physician) will call subjects before the PET Scan Session to review the study procedures and risks and answer any questions subjects might have. PET Scan Session. Subjects will receive a telephone call the day before the session to remind them to stop smoking at 9:00pm that night. At the session, they will provide a series of samples. These include: * A urine sample to assess for the presence of study-prohibited drugs and medications (including cocaine, opiates, benzodiazepines, amphetamines, methamphetamines, tri-cyclic antidepressants, methadone, PCP, and barbiturates). * Women of childbearing age will be required to take a urine pregnancy test. * A breath alcohol concentration (BrAC) measurement. * A breath carbon monoxide (CO) reading. * Have your weight measured. After subjects arrive at the PET center, they will have two intravenous (I.V.) lines placed. A sterile solution will be dripped through the tubing to keep them open. Subjects will have blood pressure and heart rate taken prior to injection and three 10ml tubes of blood will be drawn to determine the baseline levels of radioactive tracer. After this, subjects will be injected with a radioactive tracer (a chemical that has a radioactive molecule attached to it) called 2-\[18F\]FA that will be pumped through one of the I.V. lines over an 8-hour period. During the waiting period subjects will complete two questionnaires, a brief IQ test, and five computer games. They will have repeated blood pressure and heart rate readings taken soon after the initial injection and every 45 minutes afterwards. The investigators will draw 3 ml (half a teaspoon) of blood from the second I.V. line every 15-30 minutes to measure radiotracer levels. Just prior to beginning the scan, subjects will be asked two questions about cravings. These questions will be asked every 30 minutes during the scan and then once more after subjects have exited the scan. The investigators will draw one 3ml tube of blood at the beginning of the PET scan and every 30 min during the PET scan (total 5 teaspoons) from the second I.V. line to measure radiotracer levels.
Interventions
None listed
Sponsors
Study design
Eligibility
Exclusion criteria
In addition to the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acetylcholinergic Nicotine Receptor Availability as Determined by 2FA -PET Brain Imaging. | following overnight nicotine abstinence | Acetylcholinergic Nicotine Receptor availability in the thalamus is decreased in smokers with slower rates of nicotine metabolism. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cigarette Craving as Measured by the Questionnaire on Smoking Urges. | Before and immediately following the PET scan. | Measure is post-scan subtracted from pre-scan ratings. Rating is measured using the standardized, Questionnaire on Smoking Urges - Brief Version (QSU-Brief) is a standardized measure consisting of 10 statements, each rated on a Likert-like scale from 1 (Strongly Disagree) to 7 (Strongly Agree). Responses for each item are summed to produce an overall score with a range of 10-70. |
Countries
United States
Participant flow
Recruitment details
10/01/2012-03/28/2014 recruitment at the Center for Interdisciplinary Research on Nicotine Addiction at the University of Pennsylvania
Participants by arm
| Arm | Count |
|---|---|
| Normal Nicotine Metabolizers Nicotine Metabolite Radio of \> or = 0.26 | 12 |
| Slow Nicotine Metabolizers Nicotine Metabolite Radio of \< 0.26. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Normal Nicotine Metabolizers | Total | Slow Nicotine Metabolizers |
|---|---|---|---|
| Age, Continuous | 48.7 years | 47.1 years | 45.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 17 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 7 Participants | 3 Participants |
| Region of Enrollment United States | 12 Participants | 24 Participants | 12 Participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 0 / 13 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Acetylcholinergic Nicotine Receptor Availability as Determined by 2FA -PET Brain Imaging.
Acetylcholinergic Nicotine Receptor availability in the thalamus is decreased in smokers with slower rates of nicotine metabolism.
Time frame: following overnight nicotine abstinence
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Slow Metabolizers. | Acetylcholinergic Nicotine Receptor Availability as Determined by 2FA -PET Brain Imaging. | 17.5 Distribution Volume Ratio (Vt/fp) | Standard Deviation 2.4 |
| Normal Metabolizers | Acetylcholinergic Nicotine Receptor Availability as Determined by 2FA -PET Brain Imaging. | 26.8 Distribution Volume Ratio (Vt/fp) | Standard Deviation 3.1 |
Change in Cigarette Craving as Measured by the Questionnaire on Smoking Urges.
Measure is post-scan subtracted from pre-scan ratings. Rating is measured using the standardized, Questionnaire on Smoking Urges - Brief Version (QSU-Brief) is a standardized measure consisting of 10 statements, each rated on a Likert-like scale from 1 (Strongly Disagree) to 7 (Strongly Agree). Responses for each item are summed to produce an overall score with a range of 10-70.
Time frame: Before and immediately following the PET scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Slow Metabolizers. | Change in Cigarette Craving as Measured by the Questionnaire on Smoking Urges. | -8.1 units on a scale | Standard Deviation 10.1 |
| Normal Metabolizers | Change in Cigarette Craving as Measured by the Questionnaire on Smoking Urges. | 1.8 units on a scale | Standard Deviation 7.7 |