Baclofen Effects on Smoking Urge and Withdrawal

Phase 2

Terminated

Conditions: Nicotine Dependence
Nicotine Use Disorder
Tobacco Use Disorder
Smoking

Interventions: Drug: Placebo
Drug: Baclofen

Registration Number: NCT00257894

Lead Sponsor: VA Office of Research and Development

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 41

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo condition	Placebo	Placebo capsules identical to active medication, 3/day for 12 days.
Baclofen condition	Baclofen	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.