Nicotine Dependence
Conditions
Keywords
Smokers, fMRI, varenicline
Brief summary
Varenicline is the best smoking cessation agent to date; however it is only effective in a subgroup of smokers and is associated with undesirable side effects in other subgroups. To understand the underlying pharmaco-heterogeneity, the proposed project will use perfusion functional magnetic resonance imaging and a functional candidate gene association approach using brain, behavioral, and clinical endpoints in a placebo-controlled study of chronic varenicline administration in smokers. Brain and behavioral responses to smoking cues will be will be significantly greater in 9/10-repeats compared to 10/10-repeats. DAT 9/10-repeat smokers receiving varenicline will have better treatment outcome compared to 10/10-repeats. For the purposes of the clinical trial portion of the study, the change from cigarettes per day at Baseline to the last day of treatment will be reported.
Interventions
DRUGVarenicline
Varenicline will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.
DRUGPlacebo
Placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective for Varenicline: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.
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
No
Inclusion criteria
* Physically healthy male or female nicotine dependent patients ages 18-60 without other current drug dependence or psychiatric diagnosis. * Smoke ≥ 10 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 from at least 2 weeks prior to screening until 30 days after the last dose of varenicline. Examples of medically acceptable methods for this protocol include barrier (diaphragm or condom) with spermicide, an intrauterine (IUD), oral contraceptives, levonorgestrel implant, or complete abstinence. * Subjects provide voluntary informed consent. * Subjects must read at 8th grade level or higher.
Exclusion criteria
* History of head trauma or injury causing loss of consciousness, lasting more than three (3) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI. * Presence of magnetically active prosthetics, plates, pins, permanent retainer, bullets, etc. in patient's body (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. * Self report of HIV positive and on medication for symptoms: Determined on an individual basis by results from the physical examination and final approval by the study physician. * Symptomatic presence of other hematological disease. * Clinically significant hepatic (liver), renal (kidney), neurological, or endocrinological abnormalities. * History of any cardiovascular event within the last 6 months and any serious/significant cardiovascular event in the subject's life. This will be determined on an individual basis by the study physician. * History of psychosis or seizures. * Use of medications or natural herbs that may cause sedation or may effect the brain systems that are being studied (medication use will be evaluated on a case-by-case basis). * Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cigarettes Per Day | last week of treatment (1-8 weeks) | Cigarettes per day at Baseline versus 8 weeks of treatment, placebo-controlled |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 1/2012-7/2015. Methods used to recruit were flyers, advertisements on public transportation, Craigslist, word of mouth. 596 potential subjects were phone screened, 124 of those successfully consented, 43 were randomized
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants will receive either varenicline or placebo
Varenicline or placebo: Varenicline or placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks. | 22 |
| Varenicline Subjects will receive either varenicline or placebo
Varenicline or placebo: Varenicline or placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks. | 21 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Varenicline | Total |
|---|---|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 11.1 | 36.2 years STANDARD_DEVIATION 11.9 | 38.1 years STANDARD_DEVIATION 1.8 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 15 Participants | 8 Participants | 23 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Mixed Race | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic | 18 Participants | 21 Participants | 39 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 12 Participants | 18 Participants |
| Region of Enrollment United States | 22 participants | 21 participants | 43 participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 21 |
| other Total, other adverse events | 13 / 22 | 8 / 21 |
| serious Total, serious adverse events | 0 / 22 | 0 / 21 |
Outcome results
Primary
Cigarettes Per Day
Cigarettes per day at Baseline versus 8 weeks of treatment, placebo-controlled
Time frame: last week of treatment (1-8 weeks)
Population: Population was the number of randomized subjects who participated in any treatment length. One subject per group was not included in this analysis as one withdrew a few days after their first scan and the other was lost to follow up after their first scan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Cigarettes Per Day | Baseline | 15.7 cigarettes per day | Standard Error 2.5 |
| Placebo | Cigarettes Per Day | Following Treatment | 9.8 cigarettes per day | Standard Error 2.6 |
| Varenicline | Cigarettes Per Day | Baseline | 14.3 cigarettes per day | Standard Error 1.8 |
| Varenicline | Cigarettes Per Day | Following Treatment | 5.3 cigarettes per day | Standard Error 1.6 |
p-value: 0.0004t-test, 2 sided
p-value: 0.1t-test, 2 sided