Nicotine Dependence, Nicotine Use Disorder, Smoking, Tobacco Use Disorder
Conditions
Keywords
Baclofen, Conditioning, Classical, Nicotine, Smoking
Brief summary
The purpose of this study is to determine whether baclofen is effective in reducing smoking urge, withdrawal, and reinforcement in moderate to heavy cigarette smokers.
Detailed description
OBJECTIVES: The long-term objective of this research program is to improve treatments for tobacco smokers by investigating the effects of medications on self-reported and psychophysiological responses to smoking cues and on behavioral-economic measures of smoking reinforcement during a period of tobacco deprivation. The specific objectives of the present application are to investigate the dose-response effects of baclofen (a gamma-aminobutyric acid B agonist), 1) on urge, and withdrawal, and 2) on the reinforcement value of smoking as measured by choices for puffs on cigarettes versus an alternative reinforcer among current smokers after 4 hours of smoking deprivation. RESEARCH PLAN: The study will use a randomized placebo-controlled between-subjects design with 64 smokers to investigate the effects of placebo and two doses (20 or 40 mg/day) of baclofen on urge to smoke and withdrawal and on choices for smoking versus money after 4 hours of deprivation. METHODS: Participants will be healthy people who smoke at least 10 cigarettes per day and who are motivated for future smoking cessation. On Day 0, a baseline session will occur after 4 hours of smoking deprivation and on Day 10 of medication the same assessments will be repeated after the final medication dose has been stabilized for at least 3 days and after 4 hours of supervised smoking deprivation has occurred. Medication differences in urge and withdrawal and in the reinforcement value of smoking cigarettes will be investigated. Dependent measures of urge and withdrawal will be by self-report. The dependent measure of reinforcement value is the ratio of choices for cigarette puffs versus money during a subsequent 2-1/2 hr period. The choice procedure will clarify the relative reinforcement value of smoking while controlling for non-specific decreases in general activity level resulting from sedation. Nicotine self-administration during the medication period will be quantified using saliva cotinine, as a secondary effect. CLINICAL RELEVANCE: More effective interventions for tobacco use could result in less suffering and mortality and in considerable savings in health care costs associated with cardiovascular disease, pulmonary disorders, and cancer.
Interventions
DRUGBaclofen
Dosing taken orally for a total of 12 days: 40mg/day vs. 0mg/day (placebo tabs). The 40mg condition will receive 15mg/day the first 3 days(Days 1,2,3), 30mg/day for 3 days(Days 4,5,6), and 40mg/day for 3 days(Days 7,8,9). Downward titration: 40mg/day condition will receive 40mg/day(Day 10), 20mg/day(Day 11), and 10mg/day(Day 12).
DRUGPlacebo
Matched placebo capsules containing inert filler taken orally for a total of 12 days
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Smoke at least 10 cigarettes per day for at least 6 months and considering quitting smoking in the next 6 months-
Exclusion criteria
* Planning to attempt smoking cessation within the next 4 months * Weight less than 110 lbs. or above 220 lbs. * Use of tobacco products other than cigarettes in the previous month. * History of: Kidney disease, uncontrolled conditions (e.g., cardiac disease, pulmonary disease, diabetes, hypertension) Neurological disease (including stroke, mini-stroke, brain injury, Alzheimers Disease, encephalitis, meningitis, seizure disorder),Phenylketonuria Schizophrenia, Schizoaffective Disorder, Paranoid Disorder, or Schizotypal Disorder. * Current alcohol and/or drug use disorder as indicated by a screening questionnaire, past treatment for alcohol or substance use problems unless in remission(clean and sober for past year or more) or intention to seek treatment in the next 6 months for alcohol or substance use problems. * For women: Pregnancy, nursing, not using a reliable form of birth control. * Allergy to baclofen, Lioresal, or Kemstro. * Taking the following medications: antidepressants(excluding selective serotonin reuptake inhibitors), bupropion, phenothiazines, antihistamines, sedative/hypnotics, benzodiazepines, alpha blockers, beta blockers. * Lives with someone enrolled in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Score on Questionnaire of Smoking Urges | Measures are assessed on the tenth day of medication titration, after 5 hours of smoking deprivation. | Questionnaire of Smoking Urges assesses cravings to smoke. the score is the mean of 10 7-point Likert ratings so the range of the total score is from 1 (no urge) to 7 (intense urge). These data are only available on the subset of participants who participated through Day 10. |
| Minnesota Nicotine Withdrawal Questionnaire | Day 10 | Measure of degree of nicotine withdrawal at the time. Scored as the mean of 8 5-point ratings so the total score ranges from 0 (no withdrawal) to 4 (severe withdrawal). These data are only available on the subset of participants who participated through Day 10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Self-administration as Quantified by Carbon Monoxide Boost During a Behavioral Self-administration Task. | Measures are assessed on the tenth day of medication titration, after 5 hours of smoking deprivation. | Expired carbon monoxide (CO) assessed before and after a 2.5-h period when they make choices for cigarette puffs versus money. CO Boost is the difference score, possibly ranging from -25 (improved) to +25 (worse). These data are only available on the subset of participants who participated through Day 10.. |
| Cigarette Choice Task | Tenth day of medication titration | At 20 times spaced over a 2.5 h period, participants chose between smoking two puffs (of pre-determined size) of a cigarette and receiving US$0.10. The primary behavioral outcome measure was number of cigarette choices, ranging from 0 (no smoking) to 20 (smoking the most allowed). These data are only available on the subset of participants who participated through Day 10. |
Countries
United States
Participant flow
Recruitment details
Participants were veterans recruited from the Veterans Affairs Medical Center, Veterans Affairs Medical Center staff, visitors, and smokers recruited from the community.
Pre-assignment details
Nine people washed out or failed to return before assignment to groups, or were assessed with an invalid informed consent so the IRB required their data to be excluded from all analyses, and no demographic information is available on these people, leaving n = 32 with at least age and gender.
Participants by arm
| Arm | Count |
|---|---|
| Baclofen Condition Baclofen taken orally for 12 days total up to 40 mg/day maximum, divided into 3 equal portions each day. Participants receive 12 mg/day the first 3 days, 30 mg/day the next 3 days, and 40 mg/day on Days 7, 8, 9. Testing is on day 10 after the first dose is taken, with downward titration days 10-12 of 30 mg on Day 10, 20 mg on Day 11 and 10 mg on Day 12. | 17 |
| Placebo Condition Placebo capsules identical to active medication, 3/day for 12 days. | 15 |
| Total | 32 |
Baseline characteristics
| Characteristic | Baclofen Condition | Placebo Condition | Total |
|---|---|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 10.7 | 43.5 years STANDARD_DEVIATION 9.8 | 45.6 years STANDARD_DEVIATION 10.3 |
| Fagerstrom Test for Nicotine Dependence | 6.18 units on a scale STANDARD_DEVIATION 1.59 | 5.93 units on a scale STANDARD_DEVIATION 2.76 | 6.06 units on a scale STANDARD_DEVIATION 2.18 |
| Number of cigarettes smoked per day | 20.4 cigarettes STANDARD_DEVIATION 7.6 | 19.0 cigarettes STANDARD_DEVIATION 8.1 | 19.7 cigarettes STANDARD_DEVIATION 7.8 |
| Number of years smoked daily | 28.5 years STANDARD_DEVIATION 11.9 | 24.9 years STANDARD_DEVIATION 11.7 | 26.9 years STANDARD_DEVIATION 11.7 |
| Region of Enrollment United States | 17 participants | 15 participants | 32 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 8 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 20 |
| serious Total, serious adverse events | 0 / 21 | 1 / 20 |
Outcome results
Primary
Minnesota Nicotine Withdrawal Questionnaire
Measure of degree of nicotine withdrawal at the time. Scored as the mean of 8 5-point ratings so the total score ranges from 0 (no withdrawal) to 4 (severe withdrawal). These data are only available on the subset of participants who participated through Day 10.
Time frame: Day 10
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen Condition | Minnesota Nicotine Withdrawal Questionnaire | 1.06 units on a scale | Standard Deviation 1.73 |
| Placebo Condition | Minnesota Nicotine Withdrawal Questionnaire | 1.58 units on a scale | Standard Deviation 2.35 |
Comparison: Analysis of variance, group by time (Day 0 vs. Day 10).p-value: 0.21ANOVA
Primary
Total Score on Questionnaire of Smoking Urges
Questionnaire of Smoking Urges assesses cravings to smoke. the score is the mean of 10 7-point Likert ratings so the range of the total score is from 1 (no urge) to 7 (intense urge). These data are only available on the subset of participants who participated through Day 10.
Time frame: Measures are assessed on the tenth day of medication titration, after 5 hours of smoking deprivation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen Condition | Total Score on Questionnaire of Smoking Urges | 5.5 units on a scale | Standard Deviation 2.1 |
| Placebo Condition | Total Score on Questionnaire of Smoking Urges | 5.3 units on a scale | Standard Deviation 2.3 |
p-value: 0.57ANOVA
Secondary
Cigarette Choice Task
At 20 times spaced over a 2.5 h period, participants chose between smoking two puffs (of pre-determined size) of a cigarette and receiving US$0.10. The primary behavioral outcome measure was number of cigarette choices, ranging from 0 (no smoking) to 20 (smoking the most allowed). These data are only available on the subset of participants who participated through Day 10.
Time frame: Tenth day of medication titration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen Condition | Cigarette Choice Task | 15.4 choices | Standard Deviation 5.7 |
| Placebo Condition | Cigarette Choice Task | 18.2 choices | Standard Deviation 4.8 |
p-value: 0.79ANOVA
Secondary
Nicotine Self-administration as Quantified by Carbon Monoxide Boost During a Behavioral Self-administration Task.
Expired carbon monoxide (CO) assessed before and after a 2.5-h period when they make choices for cigarette puffs versus money. CO Boost is the difference score, possibly ranging from -25 (improved) to +25 (worse). These data are only available on the subset of participants who participated through Day 10..
Time frame: Measures are assessed on the tenth day of medication titration, after 5 hours of smoking deprivation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baclofen Condition | Nicotine Self-administration as Quantified by Carbon Monoxide Boost During a Behavioral Self-administration Task. | 4.69 units on a scale | Standard Deviation 4.16 |
| Placebo Condition | Nicotine Self-administration as Quantified by Carbon Monoxide Boost During a Behavioral Self-administration Task. | 5.27 units on a scale | Standard Deviation 5.9 |
p-value: 0.6ANOVA