Smoking Cessation
Conditions
Keywords
D-cycloserine, Smoking cues, Cognitive remediation, physiologic reactivity, craving
Brief summary
One hundred seventy-five eligible participants will be enrolled with aim of randomizing 60 to a double-blind, placebo-controlled trial of D-cycloserine added to cue-exposure treatment to prevent relapse to smoking. Subjects who sign an informed consent, meet inclusion criteria, and demonstrate response to cue reactivity at the screening visit, will either be: * started on approximately 3 weeks of either nicotine replacement therapy (NRT) at a dose of either 14 or 21 mg/day or varenicline titrated to 1.0 mg bid; decision of which method to use to quit smoking will be based on participant choice as well as taking into account any medical contraindications to either therapy. * evaluated to confirm abstinence from smoking. Recently abstinent participants referred by a smoking cessation clinic, PCP or self referred must have an expired air CO \< 10 ppm to confirm abstinence. Subjects who are able to demonstrate 18-24 hours of abstinence prior to the first Cue Exposure Therapy Visit (CET I) will be eligible to be randomized to two visits of study medication and cue exposure treatment, spaced five to nine days apart. Subjects will complete 2 follow-up visits at 2-4 days and four weeks after the last CET visit. The entire study involves twelve visits and will last approximately ten weeks. For recently abstinent participants referred by a smoking cessation clinic, PCP or self referred, the study involves 7 visits (screening and baseline visit will be merged into one and there is no CBT component) and will last approximately 7 weeks.
Interventions
DRUGD-cycloserine
2 single weekly doses, 50 mg capsule
DRUGPlacebo
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants must have smoked an average of ≥ 10 cigarettes/day during the past 6 months * have expired air CO ≥ 10 ppm or urine cotinine ≥ 100 ng/mL * meet DSM-IV criteria for nicotine dependence * aged 18 - 65 * Recently abstinent participants referred by a PCP, smoking cessation clinic or self referred must have an expired air CO \< 10 ppm to confirm abstinence
Exclusion criteria
* Severe or uncontrolled medical or psychiatric illness * History of multiple hospitalizations within the last six months for an ongoing medical condition * Any significant, current and unstable cardiovascular disease, end stage renal failure, severe COPD requiring oxygen, any current unstable neurological disease, a history of seizures or epilepsy, or a history of head trauma with lasting neurological sequelae, will be excluded for their safety. * Major depressive episode, mania or mixed episode in the prior 6 months * Lifetime history of psychosis, delusional disorder, organic mental disorder by DSM-IV criteria, or ongoing cognitive impairment will also be excluded for their safety, * Current excessive use of alcohol (\>21 drinks/week in female subjects; \>28 drinks/week in male subjects) * Current use of illicit drugs. * Current steroid use, current, daily use of benzodiazepines, or participants who are unwilling to modify their benzodiazepine use will. * Pregnant or breastfeeding women will be excluded, as well as women of childbearing potential who will not use a medically acceptable method of contraception (i.e. IUD, oral contraceptives). * Participants who are deaf, blind, or experience any other significant sensory impairment that would preclude them from completing study procedures will also be excluded, as well as participants who are unable to understand study procedures or provide informed consent. * Participants receiving isoniazid or ethionamide, or who have a known sensitivity to D-cycloserine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of D-cycloserine + Cue-exposure Treatment on Continuous Abstinence From Tobacco Smoking. | Up to 6 weeks | Participants assigned to receive D-cycloserine + CET will achieve better maintenance of tobacco abstinence, as assessed with self-report and saliva cotinine measurements, than those who receive placebo + CET at week 6 follow up visits |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of D-cycloserine + Cue-exposure Treatment on Skin Conductance | 6 weeks | Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (skin conductance) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Assessment of skin conductance was made after each audio recording was presented. The skin conductance mean was obtained for each script (smoking vs neutral). Differences in responsivity (skin conductance) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET. |
| Effect of D-cycloserine + Cue-exposure Treatment on Heart Rate | 6 weeks | Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (heart rate) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Heart rate measurement was obtained after each audio recording was presented. The heart rate mean was obtained for each script (smoking vs neutral). Differences in responsivity (heart rate) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET. |
| Effect of D-cycloserine + Cue-exposure Treatment on Electromyogram | 6 weeks | Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (electromyogram) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Electromyogram of the corrugator (EMGc)measurement was obtained after each audio recording was presented. The EMGc mean was obtained for each script (smoking vs neutral). Differences in responsivity (EMGc) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET. |
| Effect of D-cycloserine + Cue-exposure Treatment on Craving | 6 weeks | Recently abstinent smokers assigned to receive D-cycloserine + CET will have less craving at the Post-Extinction Assessment than those who receive placebo + CET The scale used to measure craving was a Visual Analogue Scale 0 (no desire at all) - 7 (unable to resist) Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Craving level was obtained after each audio recording was presented. The craving mean was obtained for each script (smoking vs neutral). Differences in craving level response to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET. |
| Effect of D-cycloserine + Cue-exposure Treatment on Attentional Bias Toward Smoking Cuesmeasured With the Emotional Stroop Task | Baseline and week 6 | Recently abstinent smokers assigned to receive D-cycloserine + CET will have less attentional bias (Smoking Stroop task) toward smoking cues at the Post-Extinction Assessment than those who receive placebo + CET The Emotional Stroop uses smoking-related words and neutral words to measure attentional bias toward smoking related cues. Attentional bias is a central feature of many cognitive theories of addiction and can be measured with an emotional analog of the Stroop task. In this task, participants name the colors in which words are printed, and the words vary in their relevance to smoking. Extensive research has shown that patients are often slower to name the color of a word associated with concerns relevant to their clinical condition due to distraction by the meaning of the word(Williams, Mathews et al. 1996). The Stroop interference Score is obtained by subtracting Reaction Time (RT) to smoking minus the Reaction Time to neutral |
Countries
United States
Participant flow
Recruitment details
One hundred fifty participants were enrolled (signed consent), but only 98 were found eligible and started study procedures. Eighty one participants started smoking cessation CBT, and 62 finished and were randomized to receive either D-cycloserine or identical placebo added to exposure treatment to prevent relapse to smoking.
Pre-assignment details
Participants received their choice of nicotine patch or varenicline (0.5 mg per day for 3 days, 0.5 mg bid for 4 days, 1 mg bid for 4 wks) and weekly cognitive behavioral therapy for smoking cessation.
Participants by arm
| Arm | Count |
|---|---|
| Placebo 50 mg capsule,single dose, twice, one week apart, by mouth
Placebo | 32 |
| D-cycloserine 50 mg capsule,single dose, twice, one week apart, by mouth
D-cycloserine: 2 single weekly doses, 50 mg capsule | 30 |
| Total | 62 |
Baseline characteristics
| Characteristic | Placebo | D-cycloserine | Total |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 11.4 | 48.4 years STANDARD_DEVIATION 12.4 | 47.7 years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 19 Participants | 22 Participants | 41 Participants |
| Sex: Female, Male Male | 13 Participants | 8 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 32 | 24 / 30 |
| serious Total, serious adverse events | 1 / 32 | 0 / 30 |
Outcome results
Primary
Effect of D-cycloserine + Cue-exposure Treatment on Continuous Abstinence From Tobacco Smoking.
Participants assigned to receive D-cycloserine + CET will achieve better maintenance of tobacco abstinence, as assessed with self-report and saliva cotinine measurements, than those who receive placebo + CET at week 6 follow up visits
Time frame: Up to 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Effect of D-cycloserine + Cue-exposure Treatment on Continuous Abstinence From Tobacco Smoking. | 9 percentage of participants |
| D-cycloserine | Effect of D-cycloserine + Cue-exposure Treatment on Continuous Abstinence From Tobacco Smoking. | 30 percentage of participants |
Secondary
Effect of D-cycloserine + Cue-exposure Treatment on Attentional Bias Toward Smoking Cuesmeasured With the Emotional Stroop Task
Recently abstinent smokers assigned to receive D-cycloserine + CET will have less attentional bias (Smoking Stroop task) toward smoking cues at the Post-Extinction Assessment than those who receive placebo + CET The Emotional Stroop uses smoking-related words and neutral words to measure attentional bias toward smoking related cues. Attentional bias is a central feature of many cognitive theories of addiction and can be measured with an emotional analog of the Stroop task. In this task, participants name the colors in which words are printed, and the words vary in their relevance to smoking. Extensive research has shown that patients are often slower to name the color of a word associated with concerns relevant to their clinical condition due to distraction by the meaning of the word(Williams, Mathews et al. 1996). The Stroop interference Score is obtained by subtracting Reaction Time (RT) to smoking minus the Reaction Time to neutral
Time frame: Baseline and week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Effect of D-cycloserine + Cue-exposure Treatment on Attentional Bias Toward Smoking Cuesmeasured With the Emotional Stroop Task | 35.27 Stroop interference Score | Standard Deviation 74.93 |
| D-cycloserine | Effect of D-cycloserine + Cue-exposure Treatment on Attentional Bias Toward Smoking Cuesmeasured With the Emotional Stroop Task | 50.30 Stroop interference Score | Standard Deviation 74.85 |
p-value: 0.473t-test, 2 sided
Secondary
Effect of D-cycloserine + Cue-exposure Treatment on Craving
Recently abstinent smokers assigned to receive D-cycloserine + CET will have less craving at the Post-Extinction Assessment than those who receive placebo + CET The scale used to measure craving was a Visual Analogue Scale 0 (no desire at all) - 7 (unable to resist) Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Craving level was obtained after each audio recording was presented. The craving mean was obtained for each script (smoking vs neutral). Differences in craving level response to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Effect of D-cycloserine + Cue-exposure Treatment on Craving | 2.28 change in units on a scale | Standard Deviation 2.3 |
| D-cycloserine | Effect of D-cycloserine + Cue-exposure Treatment on Craving | 1.44 change in units on a scale | Standard Deviation 1.87 |
p-value: 0.123ANOVA
Secondary
Effect of D-cycloserine + Cue-exposure Treatment on Electromyogram
Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (electromyogram) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Electromyogram of the corrugator (EMGc)measurement was obtained after each audio recording was presented. The EMGc mean was obtained for each script (smoking vs neutral). Differences in responsivity (EMGc) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Effect of D-cycloserine + Cue-exposure Treatment on Electromyogram | 0.25 change in micro volts | Standard Deviation 1.02 |
| D-cycloserine | Effect of D-cycloserine + Cue-exposure Treatment on Electromyogram | 0.46 change in micro volts | Standard Deviation 1.52 |
p-value: 0.818ANOVA
Secondary
Effect of D-cycloserine + Cue-exposure Treatment on Heart Rate
Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (heart rate) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Heart rate measurement was obtained after each audio recording was presented. The heart rate mean was obtained for each script (smoking vs neutral). Differences in responsivity (heart rate) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Effect of D-cycloserine + Cue-exposure Treatment on Heart Rate | -0.13 change in beats per minute | Standard Deviation 2.64 |
| D-cycloserine | Effect of D-cycloserine + Cue-exposure Treatment on Heart Rate | 0.98 change in beats per minute | Standard Deviation 2.34 |
p-value: 0.94ANOVA
Secondary
Effect of D-cycloserine + Cue-exposure Treatment on Skin Conductance
Recently abstinent smokers assigned to receive D-cycloserine + CET will have less physiologic (skin conductance) reactivity to smoking cues at the Post-Extinction Assessment than those who receive placebo + CET. Subjects were presented with 2 blocks of audio recordings, one smoking-related script and one neutral script unrelated to smoking. Assessment of skin conductance was made after each audio recording was presented. The skin conductance mean was obtained for each script (smoking vs neutral). Differences in responsivity (skin conductance) to smoking cues (smoking script) was compared between subjects who received D-cycloserine + CET and subjects who received placebo + CET.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Effect of D-cycloserine + Cue-exposure Treatment on Skin Conductance | 0.14 change in microSiemens | Standard Deviation 0.46 |
| D-cycloserine | Effect of D-cycloserine + Cue-exposure Treatment on Skin Conductance | 0.18 change in microSiemens | Standard Deviation 0.31 |
p-value: 0.574ANOVA
p-value: 0.747ANOVA