Baclofen Effects on Smoking Urge and Withdrawal

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Terminated
• CT.gov ID: NCT00257894
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Nicotine Use Disorder; Nicotine Dependence; Smoking; Tobacco Use Disorder	Drug: Baclofen; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Baclofen Effects on Smoking Urge and Withdrawal
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Baclofen; 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).; Other Names: Seroquel
Placebo Comparator: Placebo condition Placebo capsules identical to active medication, 3/day for 12 days.	Drug: Placebo; Matched placebo capsules containing inert filler taken orally for a total of 12 days

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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..

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Medical Center, Providence	Providence	Rhode Island	United States	02908

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Damaris Rohsenow, PhD, VA Medical Center, Providence

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT00257894
• Other Study ID Numbers: NEUA-029-04F
• First Posted: Nov 23, 2005
• Last Update Posted: Nov 4, 2015
• Last Verified: Oct 1, 2015

• Keywords provided by VA Office of Research and Development: Baclofen; Conditioning, Classical; Nicotine; Smoking
• Additional relevant MeSH terms: Disease; Tobacco Use Disorder; Baclofen

Study Results

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 Detail	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.

Arm/Group Title	Baclofen Condition	Placebo Condition
Arm/Group Description	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.	Placebo capsules identical to active medication, 3/day for 12 days.
Period Title: Overall Study
STARTED	21	20
COMPLETED	17	15
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Baclofen Condition	Placebo Condition	Total
Arm/Group Description	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.	Placebo capsules identical to active medication, 3/day for 12 days.	Total of all reporting groups
Overall Participants	17	15	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.4 (10.7)	43.5 (9.8)	45.6 (10.3)
Sex: Female, Male (Count of Participants)
Female	6 35.3%	7 46.7%	13 40.6%
Male	11 64.7%	8 53.3%	19 59.4%
Region of Enrollment (participants) [Number]
United States	17 100%	15 100%	32 100%
Fagerstrom Test for Nicotine Dependence (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.18 (1.59)	5.93 (2.76)	6.06 (2.18)
Number of cigarettes smoked per day (cigarettes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cigarettes]	20.4 (7.6)	19.0 (8.1)	19.7 (7.8)
Number of years smoked daily (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.5 (11.9)	24.9 (11.7)	26.9 (11.7)

Outcome Measures

1. Primary Outcome

Title	Total Score on Questionnaire of Smoking Urges
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen Condition	Placebo Condition
Arm/Group Description	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.	Placebo capsules identical to active medication, 3/day for 12 days.
Measure Participants	16	11
Mean (Standard Deviation) [units on a scale]	5.5 (2.1)	5.3 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baclofen Condition, Placebo Condition
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.57
	Comments	Effect size close to zero (eta squared of .01)
	Method	ANOVA
	Comments	Interaction effect term from group by time ANOVA

2. Secondary Outcome

Title	Nicotine Self-administration as Quantified by Carbon Monoxide Boost During a Behavioral Self-administration Task.
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen Condition	Placebo Condition
Arm/Group Description	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.	Placebo capsules identical to active medication, 3/day for 12 days.
Measure Participants	16	11
Mean (Standard Deviation) [units on a scale]	4.69 (4.16)	5.27 (5.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baclofen Condition, Placebo Condition
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.60
	Comments	Effect size about zero (eta squared = .01)
	Method	ANOVA
	Comments	Interaction term from a group by time ANOVA

3. Secondary Outcome

Title	Cigarette Choice Task
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen Condition	Placebo Condition
Arm/Group Description	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.	Placebo capsules identical to active medication, 3/day for 12 days.
Measure Participants	16	11
Mean (Standard Deviation) [choices]	15.4 (5.7)	18.2 (4.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baclofen Condition, Placebo Condition
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.79
	Comments	Effect size (eta squared) = 0
	Method	ANOVA
	Comments	Interaction term of a group by time ANOVA

4. Primary Outcome

Title	Minnesota Nicotine Withdrawal Questionnaire
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen Condition	Placebo Condition
Arm/Group Description	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.	Placebo capsules identical to active medication, 3/day for 12 days.
Measure Participants	16	12
Mean (Standard Deviation) [units on a scale]	1.06 (1.73)	1.58 (2.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baclofen Condition, Placebo Condition
	Comments	Analysis of variance, group by time (Day 0 vs. Day 10).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.21
	Comments	For test of drug by time interaction effect
	Method	ANOVA
	Comments	Medium effect size, eta squared = .061

Adverse Events

Time Frame	1 year 11 months
Adverse Event Reporting Description	Jan. 2007 - Nov. 2008
Arm/Group Title	Baclofen Condition		Placebo Condition
Arm/Group Description	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.		Placebo capsules identical to active medication, 3/day for 12 days.
All Cause Mortality
	Baclofen Condition		Placebo Condition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Baclofen Condition		Placebo Condition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		1/20 (5%)
Musculoskeletal and connective tissue disorders
Hospitalization	0/21 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Baclofen Condition		Placebo Condition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.