Smoking
Conditions
Brief summary
A total of 20 subjects will participate in this four week, between groups, double-blind, placebo controlled study. Subjects will participate in two experimental sessions separated by approximately one week. Subjects will be randomized to receive either 50 mg cycloserine or placebo combined with cue exposure. Several physiological and subjective outcome measures (e.g., heart rate, blood pressure, galvanic skin response) will be obtained during the sessions. Experimental sessions will last approximately 4.5 hours with follow-up sessions lasting approximately thirty minutes. Our aims are: 1. To examine the effect of cycloserine vs. placebo on extinction of smoking cue reactivity in overnight abstinent smokers. Reactivity to smoking cues will be captured with self-report smoking urges and physiological measures (heart rate, blood pressure, and skin conductance). We hypothesize that cycloserine, relative to placebo, will facilitate extinction of smoking cue reactivity. 2. To examine the effect of cycloserine vs. placebo when combined with two 4.5 hour laboratory cue exposure training sessions, on smoking behavior in smokers. Smoking behavior will be measured with self-report smoking and saliva cotinine levels. 3. To examine the effect of cycloserine vs. placebo on memory performance in nicotine dependent smokers. Memory performance will be measured with verbal learning, recognition and recall tasks. 4\) To examine the safety and tolerability of cycloserine treatment in smokers. We hypothesize that cycloserine will be well tolerated by smokers.
Interventions
DRUGCycloserine
50 mg Cycloserine given in two separate experimental sessions separated by approximately one week.
DRUGPlacebo
Matched placebo for subjects randomized to placebo arm. Given in two experimental sessions separated by approximately one week.
Sponsors
VA Connecticut Healthcare System
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* female and male smokers, aged 18 to 55 years; * history of smoking daily for the past 12 months, at least 10 cigarettes daily; * CO level \> 10ppm; * for women: not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods other than OCP; * Non-treatment seeking nicotine dependent smokers.
Exclusion criteria
* history of heart disease, renal or hepatic diseases or other medical conditions that the physician investigator deems as contraindicated for the patient to be in the study; * regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) and/or recent psychiatric diagnosis and treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia and panic disorder within the past year; * current dependence on alcohol or on drugs other than nicotine; * regular use of any other tobacco products than cigarettes, including smokeless tobacco and nicotine products; * allergy to cycloserine; * subjects with epilepsy or a history of seizures; * Treatment seeking nicotine dependent smokers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cigarettes Smoked Per Day | 1 week follow-up | The number of cigarettes smoked per day at the 1 week follow up time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cigarettes Smoked Per Day | 4 Week Followup | The number of cigarettes smoked per day at the 4-week follow up timepoint. |
| Urinary Cotinine Level | 4 Week Follow-up Timepoint | Urinary Cotinine level at the 4-week follow up timepoint |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cycloserine 50 mg cycloserine | 12 |
| Placebo Matched placebo | 13 |
| Total | 25 |
Baseline characteristics
| Characteristic | Placebo | Cycloserine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 12 Participants | 25 Participants |
| Age Continuous | 41.5 years STANDARD_DEVIATION 11.5 | 41.1 years STANDARD_DEVIATION 6.2 | 41.3 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment United States | 13 participants | 12 participants | 25 participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Cigarettes Smoked Per Day
The number of cigarettes smoked per day at the 1 week follow up time point.
Time frame: 1 week follow-up
Population: The number of participants used for analysis were those who completed the 4-week follow-up timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycloserine | Cigarettes Smoked Per Day | 10.3 Cigarettes per day | Standard Deviation 6.3 |
| Placebo | Cigarettes Smoked Per Day | 13.9 Cigarettes per day | Standard Deviation 12.7 |
Secondary
Cigarettes Smoked Per Day
The number of cigarettes smoked per day at the 4-week follow up timepoint.
Time frame: 4 Week Followup
Population: The number of subjects in the study at the 4-week timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycloserine | Cigarettes Smoked Per Day | 9.9 Cigarettes per day | Standard Deviation 7.7 |
| Placebo | Cigarettes Smoked Per Day | 11.0 Cigarettes per day | Standard Deviation 9.2 |
Secondary
Urinary Cotinine Level
Urinary Cotinine level at the 4-week follow up timepoint
Time frame: 4 Week Follow-up Timepoint
Population: Subjects used for analysis are those who reached the 4 week followup timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycloserine | Urinary Cotinine Level | 1645.5 Mean ng/ml | Standard Deviation 1180.8 |
| Placebo | Urinary Cotinine Level | 2062.6 Mean ng/ml | Standard Deviation 1091.1 |