Insomnia, Nicotine Dependence
Conditions
Keywords
insomnia, nicotine dependence, smoking, smoking cessation, zyban
Brief summary
Objectives: The primary objective of this study is to determine the efficacy of eszopiclone at treating sleep problems related to withdrawal from nicotine in healthy smokers attempting smoking cessation. Sleep disturbances are a significant problem for smokers who are trying to quit smoking. Smokers may be more likely to have sleep problems and both nicotine withdrawal and agents used to aid smoking cessation (e.g., pharmacotherapies) may disrupt sleep. Lunesta (eszopiclone) is a medication that has been approved by the FDA to treat insomnia. Eszopiclone's efficacy for treating insomnia makes it a promising agent for treating nicotine withdrawal-related symptoms of sleep disturbance. This study will be 7 weeks duration. All participants will begin taking Zyban at the beginning of week 1 and will be asked to try to quit smoking at the beginning of week 2. Participants will also begin to take Lunesta or matched placebo (3 mg qd x 6 weeks) on the target quit date at the beginning of week 2. All subjects will receive eight (8) weekly sessions of brief individual supportive smoking cessation counseling. Hypothesis: It is hypothesized that significantly fewer sleep problems will be reported by participants taking Lunesta as compared to placebo. Specifically, it is expected that participants taking Lunesta will report less difficulty falling and staying asleep, higher sleep quality, and less insomnia-related fatigue and distress than participants taking placebo.
Interventions
DRUGEszopiclone
eszopiclone (lunesta) - 3 mg qd x 6 weeks, oral capsule
DRUGBupropion
bupropion SR in oral capsule will be begun at the beginning of week 1 (150 mg qd x 7 days) with an increase to the full dose (150 mg bid x 6 weeks) at the beginning of week 2.
Sponsors
Sumitomo Pharma America, Inc.
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are between ages 18-65 years old. * Meet DSM-IV criteria for nicotine dependence. * Smoke at least 15 cigarettes (3/4 pack) daily (averaged over 1 week, in the past 1 month) and have an expired breath CO level \> 10. * At the time of initial evaluation, are motivated to quit smoking in the next 30 days. * Receive a score of ≥ 10 on the Insomnia Severity Index (ISI) * Have the capacity to give informed consent, and are English-speaking.
Exclusion criteria
* Are taking an over-the-counter or prescription medications that are known to affect sleep. * Are taking medications contraindicated for use with eszopiclone or bupropion including: Ketoconazole, Itraconazole, Clarithromycin, Erythromycin, Nefazodone, Troleandomycin, Ritonavir, Nelfinavir, Trazodone, and Methadone. * Are using any over-the-counter analgesics that contain caffeine. * Have serious medical disorders that may make participation in the trial unsafe. * Are physiologically dependent on and/or abusing alcohol or other drugs of abuse (e.g., cocaine, opiates, benzodiazepines, etc.) in the past 6 months prior to randomization into the trial. * Consume greater than 1 alcoholic beverage per day or greater than 7 alcoholic drinks per week. * Meet DSM-IV criteria for a current diagnosis of major depressive disorder, panic disorder or post-traumatic stress disorder, or a current or past history bipolar disorder, schizophrenia, or anorexia or bulimia nervosa. Have a past history of major depression, with historical evidence of suicidal or homicidal behavior, or psychotic symptoms. * Have the presence of suicidal or homicidal ideation, or significant impairment of social or occupational functioning, either at study baseline during the evaluation process, or during participation in the trial. * Are from the same household as another study participant. * A history of seizures of any etiology. * A history of hypersensitivity to bupropion or Lunesta (eszopiclone).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of Insomnia as Measured by the Insomnia Severity Index | 6 weeks after target smoking quit date | Insomnia Severity Index (ISI): 13-item self-report measure which examines symptoms of insomnia, consequences of insomnia, and subjective distress related to sleep problems. Subjects rate the symptoms and consequences of insomnia on a 5 point Likert scales. For example, subjects are asked to rate the severity of their insomnia (e.g., difficulty falling asleep from 0=none to 4=very severe). Scores on the first 7 items are summed for a total insomnia score ranging from 0-28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Abstinence as Measured by Self Reported Smoking and Confirmed by CO Level | 6 weeks after target smoking quite date | Endpoint abstinence will be defined as 0 cigarettes over the seven days prior to the subject's Timeline Follow-Back evaluation at the end of week 7 (end of trial) and a Carbon Monoxide (CO) level ≤ 5. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Greater New Haven area and surrounding communities through targeted television, radio, and newspaper ads, fliers, and referrals from clinicians. Recruitment occurred between July of 2007 and October of 2008. Approximately 900 phone screens and 12 in-person screens were completed during the course of the study.
Pre-assignment details
Major reasons for exclusion at phone screen were report of no sleep problems, use of illegal substances, psychiatric or medical exclusions, and low smoking. Major reasons for exclusion during the in-person screening process included withdrawal of informed consent, alcohol or illicit drug use, and low smoking.
Participants by arm
| Arm | Count |
|---|---|
| Zyban + Lunesta Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and Eszopiclone (Lunesta; 3 mg qd x 6 weeks) | 1 |
| Zyban + Placebo Bupropion SR (Zyban; 150 mg qd x 7 days, then 150 mg bid x 6 weeks) and placebo pill (1 pill per day x 6 weeks) | 3 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Zyban + Lunesta | Zyban + Placebo | 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 | 1 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United States | 1 participants | 3 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 3 |
Outcome results
Primary
Level of Insomnia as Measured by the Insomnia Severity Index
Insomnia Severity Index (ISI): 13-item self-report measure which examines symptoms of insomnia, consequences of insomnia, and subjective distress related to sleep problems. Subjects rate the symptoms and consequences of insomnia on a 5 point Likert scales. For example, subjects are asked to rate the severity of their insomnia (e.g., difficulty falling asleep from 0=none to 4=very severe). Scores on the first 7 items are summed for a total insomnia score ranging from 0-28.
Time frame: 6 weeks after target smoking quit date
Population: Baseline descriptive data was examined for the 4 participants. Outcome measures were available for 2 participants. Due to the small number of participants, statistical comparisons were not able to be performed.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Zyban + Lunesta | Level of Insomnia as Measured by the Insomnia Severity Index | 11 Units on a Scale | Full Range 0 |
| Zyban + Placebo | Level of Insomnia as Measured by the Insomnia Severity Index | 5 Units on a Scale | Full Range 0 |
Comparison: It was hypothesized that the Zyban+Lunesta group would report lower ISI scores at end of trial than the Zyban+Placebo group.p-value: <0.05Descriptive data
Secondary
Smoking Abstinence as Measured by Self Reported Smoking and Confirmed by CO Level
Endpoint abstinence will be defined as 0 cigarettes over the seven days prior to the subject's Timeline Follow-Back evaluation at the end of week 7 (end of trial) and a Carbon Monoxide (CO) level ≤ 5.
Time frame: 6 weeks after target smoking quite date
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zyban + Lunesta | Smoking Abstinence as Measured by Self Reported Smoking and Confirmed by CO Level | 1 participants |
| Zyban + Placebo | Smoking Abstinence as Measured by Self Reported Smoking and Confirmed by CO Level | 1 participants |
Comparison: It is predicted that subjects taking eszopiclone will be more likely to report abstinence at trial endpoint than those taking placebo.p-value: <0.05Fisher Exact