Nicotine Dependence
Conditions
Keywords
Nicotine Addiction, fMRI, Baclofen
Brief summary
The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI), a functional candidate gene association approach (of dopaminergic addictions-targeted polymorphisms), and the dopamine-modulating and gamma-aminobutyric acid (GABA) B receptor agonist, baclofen, to examine the brain and behavioral responses in smokers to appetitive smoking reminders (cues that motivate continued smoking and relapse). These studies will provide a means to identify an appetitive cue-sensitive pharmacologic-responsive endophenotype. Once brain/behavioral/genetic endophenotypes can be determined prior to treatment, smoking cessation treatments can be structured to meet individual needs, which will significantly improve treatment outcome.
Interventions
DRUGBaclofen
DRUGplacebo
Sponsors
National Institute on Drug Abuse (NIDA)
National Institutes of Health (NIH)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Physically healthy, as determined by a comprehensive physical examination and approval of the study physician males or females who smoke cigarettes, ages 18-60. * Smoke ≥ 6 cigarettes per day for at least 6 months prior to study start date. * Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of child bearing potential but practicing a medically acceptable method of birth control. Examples of medically acceptable methods for this protocol include barrier (diaphragm or condom) with spermicide, an intrauterine device (IUD), the Nuvaring, oral contraceptives, levonorgestrel implant, hormonal injection or complete abstinence. * Provide voluntary informed consent. * Must be able to read. \[Subjects are required to be able to read because there are several self-administered measures that they must read, understand and provide written answers.\] * Intelligence quotient of ≥ 80.
Exclusion criteria
* History of head trauma or injury causing loss of consciousness, lasting more than five (5) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI. * Current Diagnostic and Statistical Manual-IV (DSM-IV) Axis I diagnoses other than nicotine dependence. * Presence of magnetically active irremovable prosthetics, plates, pins, permanent retainer, bullets, etc. (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body. * History of psychosis. * Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour. * Current diagnosis of or treatment within the last 3 months for alcohol dependence. * Current use of any smoking cessation treatments such as Zyban, Chantix, Wellbutrin, patch, gum, inhaler, electronic cigarettes, herbal preparations. * Vision problems that cannot be corrected with glasses. * Weight exceeding 300 pounds \[Imaging data acquisition is impaired with high weight individuals\]. * History of stroke.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cigarettes Smoked Per Day | 3 weeks (Scan Day 1, week1- Scan Day 2, week 4) | Cigarettes per day at Scan Day 2; Baclofen group vs. placebo group |
Countries
United States
Participant flow
Recruitment details
Participants were recruitment between March 2013-March 2017 via word of mouth, flyers, an online study database managed by the University of Pennsylvania, and also social media advertisements (Facebook).
Pre-assignment details
Prior to study group assignments, all participants must first provide informed consent and then are found to be eligible to participate in the study after completing the screening process. The screening process included a full physical and psychological evaluation to ensure all participants are both physically and mentally healthy enough.
Participants by arm
| Arm | Count |
|---|---|
| Sugar Pill Placebo-treated subjects will follow the identical schedule as Baclofen subjects.
placebo | 22 |
| Baclofen Baclofen will be dispensed in pill form. Baclofen will be prescribed at 20 mg 4 times per day. Each baclofen pill will be 10 mg. Thus, 2 pills will be taken at each scheduled dose for a total of 8 pills a day over a period of 8 weeks. In this way, the titration schedule, taper and potential dose reductions can be managed.
Baclofen | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 5 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Sugar Pill | Baclofen |
|---|---|---|---|
| Age, Continuous | 39.5 Years STANDARD_DEVIATION 11.9 | 40.2 Years STANDARD_DEVIATION 12.1 | 38.9 Years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized Race African American | 26 Participants | 14 Participants | 12 Participants |
| Race/Ethnicity, Customized Race Asian | 4 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Mixed Race | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White Hispanic | 4 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White Non-Hispanic | 8 Participants | 3 Participants | 5 Participants |
| Region of Enrollment United States | 44 Participants | 22 Participants | 22 Participants |
| Sex: Female, Male Female | 16 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Male | 28 Participants | 14 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 17 / 22 | 16 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Cigarettes Smoked Per Day
Cigarettes per day at Scan Day 2; Baclofen group vs. placebo group
Time frame: 3 weeks (Scan Day 1, week1- Scan Day 2, week 4)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Cigarettes Smoked Per Day | Scan Day 1 | 14.19 Cigarettes per day | Standard Error 1.01 |
| Sugar Pill | Cigarettes Smoked Per Day | Scan Day 2 | 7.67 Cigarettes per day | Standard Error 1.05 |
| Baclofen | Cigarettes Smoked Per Day | Scan Day 1 | 14.23 Cigarettes per day | Standard Error 1.2 |
| Baclofen | Cigarettes Smoked Per Day | Scan Day 2 | 7.76 Cigarettes per day | Standard Error 1.1 |