Cigarette Smoking, Tobacco Use
Conditions
Keywords
tobacco, smoking, gabapentin, abstinence
Brief summary
Gabapentin is an anti-epileptic agent that has shown preliminary evidence of efficacy for improving symptoms of cocaine and alcohol withdrawal in pilot studies. Since the neurobiology of alcohol, cocaine and nicotine withdrawal is similar, the preliminary evidence of efficacy of gabapentin for symptoms of alcohol and cocaine withdrawal suggests, that gabapentin might likely help nicotine withdrawal symptoms and thus tobacco abstinence. The effect of gabapentin on two of the neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate further suggest a potential therapeutic mechanism for gabapentin in tobacco abstinence. However, the exact mechanism of action of gabapentin is currently not known. We have recently completed an open label pilot trial of gabapentin for tobacco abstinence involving 50 smokers. The findings from that study provide promising preliminary results and suggest that further testing of gabapentin for helping cigarette smokers quit tobacco use is worth pursuing. Overall, gabapentin is well tolerated and has low abuse potential. Our goal is to evaluate novel, safe, acceptable, and effective therapies that may help increase tobacco abstinence rates. Currently, no randomized trials testing the efficacy of gabapentin for smoking abstinence have been published. While our previous study provides promising evidence regarding the potential efficacy of gabapentin for smoking abstinence, an additional dose ranging study is needed prior to pursuing a large randomized trial. The primary aim of the dose ranging study will be to obtain additional evidence of efficacy, and information on the optimal dose of gabapentin to employ in the larger randomized controlled trial.
Detailed description
A total of 120 participants will be recruited in this study and randomly assigned to one of the three groups. Participants in group A will receive gabapentin 1800-mg/day orally for 12-weeks while participants in group B will receive gabapentin 2700-mg/day orally for 12-weeks. Participants in group C will receive a matching placebo for the same duration. We have selected this dose regimen based on our experience with using gabapentin in the pilot study. The present study is designed as a randomized, blinded, placebo-controlled, three-arm, parallel-group, dose-ranging, phase II clinical trial. In addition to receiving gabapentin or placebo, all subjects will receive a brief behavioral counseling intervention during participation in the study.
Interventions
DRUGPlacebo
Placebo pill - non active sugar pill designed to look alike to the gabapentin medication
DRUGGabapentin - 1800 mg/day
gabapentin - 1800 mg/day for 12 weeks.
DRUGGabapentin - 2700 mg/day
gabapentin - 2700 mg/day for 12 weeks.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Are between 18 to 65 years of age 2. Have smoked ≥10 cigarettes/day for the past 1 year or more 3. Are willing to make a quit attempt 4. Are able to participate fully in all aspects of the study; and 5. Have been provided with, understand, and have signed the informed consent.
Exclusion criteria
1. Meet diagnostic criteria for current major depressive disorder or lifetime history of bipolar disorder or schizophrenia. Patients with mild or moderate depressive symptoms as assessed by the CES-D and determined by the physician, but who do not meet current diagnostic criteria for major depressive disorder, will be included 2. Are currently (within past 30 days) using antipsychotics, or antidepressants 3. Are currently (in previous 30 days) using any tobacco treatment program (i.e., behavioral therapy, nicotine replacement therapy, bupropion SR, clonidine, or nortriptyline) 4. Have used an investigational drug within the 30 days prior to enrolling in this study 5. Have recent history (in the past year) of alcohol abuse or dependence as assessed by the CAGE questionnaire and study investigators 6. Have a recent history of drug abuse as assessed by the Drug Abuse Screening Test 20 (DAST-20) and physician interview 7. Are pregnant, lactating, or of child bearing potential, likely to become pregnant during the medication phase and not willing to use contraception. The following birth control measures are acceptable: birth control pills, approved intra-uterine contraceptive devices, the use of two combined barrier methods (diaphragm with spermicide or condom with spermicide), injections, surgical sterilization and abstinence 8. Have a history of any major cardio-vascular events in the past 6 months including unstable angina, acute MI or coronary angioplasty 9. Have clinically significant acute or chronic progressive or unstable neurologic (myasthenia gravis), hepatic, renal, cardiovascular, respiratory (bronchospastic disease) or metabolic disease 10. Are currently on the following prescribed medications known to interact with gabapentin and unable to stop them during the study: Maalox®, cimetidine and morphine. Patients will be cautioned not to use sedatives (such as benzodiazepines, antihistamines, anti-cholinergics, trazodone, zaleplon, anti-psychotics, barbiturates, opiates, zolpidem and eszopiclone) during the study 11. Have another house-hold member or relative participating in the study 12. Have known allergy to gabapentin or its constituents; and 13. Are professional drivers or operators of heavy machinery and unable to refrain from these activities during the medication phase of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemically Confirmed 7-day Point Prevalence Abstinence From Tobacco | 12 weeks following start of medication | Point prevalence tobacco abstinence was adjudicated if the following conditions were met: (a) self-reported tobacco abstinence for the previous 7 days with a negative response to the question Have you used any type of tobacco, even a puff, in the past 7 days? and (b) Expired Carbon Monoxide equal or less then 8 parts per million. |
Countries
United States
Participant flow
Recruitment details
Recruitment began on 08/07/2007 and completed on 12/10/2008. Interested subjects who passed a phone pre-screen were seen at a medical clinic (Mayo Clinic in Rochester, MN and Franciscan Skemp Medical Center in Lacrosse, WI) for consenting and additional study procedures to determine eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo pill was identical in appearance to the active medication. Initial dosage consisted of 1 pill by mouth in the morning and night. The dose was increased over the first 2 weeks to the target frequency of three times a day. This dose was continued for the next 9 weeks and tapered in the last week. The medication was stopped at the end of 12 weeks. | 27 |
| Gabapentin - 1800 mg /Day Gabapentin was initiated at a dose of 300 mg by mouth in the morning and night. The dose was increased over the first 2 weeks to the target doses of 600 mg three times a day. This dose was continued for the next 9 weeks and tapered in the last week. The medication was stopped at the end of 12 weeks. | 27 |
| Gabapentin - 2700 mg/Day Gabapentin was initiated at a dose of 300 mg by mouth in the morning and night. The dose was increased over the first 2 weeks to the target doses of 900 mg three times a day. This dose was continued for the next 9 weeks and tapered in the last week. The medication was stopped at the end of 12 weeks. | 26 |
| Total | 80 |
Baseline characteristics
| Characteristic | Gabapentin - 1800 mg /Day | Gabapentin - 2700 mg/Day | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 26 Participants | 27 Participants | 80 Participants |
| Age Continuous | 41.1 years STANDARD_DEVIATION 9.5 | 40.7 years STANDARD_DEVIATION 13.5 | 41.0 years STANDARD_DEVIATION 11.1 | 40.9 years STANDARD_DEVIATION 11.3 |
| Cigarettes per day | 23.7 cigarettes per day STANDARD_DEVIATION 6.9 | 20.9 cigarettes per day STANDARD_DEVIATION 7.9 | 20.0 cigarettes per day STANDARD_DEVIATION 6.6 | 21.5 cigarettes per day STANDARD_DEVIATION 7.2 |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 11 Participants | 30 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 16 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 27 | 12 / 27 | 7 / 26 |
| serious Total, serious adverse events | 1 / 27 | 0 / 27 | 1 / 26 |
Outcome results
Primary
Biochemically Confirmed 7-day Point Prevalence Abstinence From Tobacco
Point prevalence tobacco abstinence was adjudicated if the following conditions were met: (a) self-reported tobacco abstinence for the previous 7 days with a negative response to the question Have you used any type of tobacco, even a puff, in the past 7 days? and (b) Expired Carbon Monoxide equal or less then 8 parts per million.
Time frame: 12 weeks following start of medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Biochemically Confirmed 7-day Point Prevalence Abstinence From Tobacco | 5 participants |
| Gabapentin - 1800 mg /Day | Biochemically Confirmed 7-day Point Prevalence Abstinence From Tobacco | 4 participants |
| Gabapentin - 2700 mg/Day | Biochemically Confirmed 7-day Point Prevalence Abstinence From Tobacco | 0 participants |
Comparison: Data were compared between treatment groups using Fisher's exact test for binary outcomes.p-value: 0.77Fisher Exact
Comparison: Data were compared between treatment groups using Fisher's exact test for binary outcomes.p-value: 1Fisher Exact