Insomnia, Migraine
Conditions
Keywords
insomnia, migraine, eszopiclone, insomnia in migraineurs
Brief summary
It is hypothesized that treating insomnia in migraineurs, many of whom also have tension headaches, prolongs total sleep time to the extent that it decreases overall headache frequency. Chronic headache sufferers also feel more tired during the day, undoubtedly affecting daytime functioning, which is hypothesized to improve as well with prolonged total sleep time.
Detailed description
The objective of the study is to determine the effect of prolonging total sleep time in migraineurs with insomnia on overall headache frequency, daytime alertness, fatigue, and functioning. The prolongation of total sleep time is accomplished by bedtime administration of 3 mg eszopiclone (Lunesta™), compared with placebo through a parallel-group design.
Interventions
DRUGeszopiclone
3 mg tablet every night at bedtime
DRUGplacebo
1 tablet every night at bedtime
Sponsors
MedVadis Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women, 18 to 64 years of age (inclusive) with International Headache Society (IHS)-II migraine with/without aura and Diagnostic and Statistical Manual (DSM)-IV primary insomnia (sleep onset/sleep maintenance). 2. Migraine frequency is 4-12 times per month, with a maximum of 20 days with headache per month, for 1 month or longer prior to screening. 3. A usual, estimated total sleep time of 6½ hours per night or less, for 1 month or longer prior to screening, due to problems falling asleep, waking up during the night, or waking up early.
Exclusion criteria
1. Abortive migraine treatment with schedule II-III opioids. 2. Use of caffeine-containing medications, prescription and non-prescription, not exceeding 10 days per month. 3. Preventive migraine treatment with tricyclics or anticonvulsants. 4. Treatment of insomnia with non-prescription medications, such as diphenhydramine, melatonin, or valerian, and prescription medications, such as hypnotics, barbiturates, benzodiazepines, sedating antihistamines, antidepressants, and antipsychotics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Sleep Time | Baseline, 6 weeks | Participants were asked to record an estimated total time asleep on a daily basis. Nightly estimates were averaged over a 2 week period for baseline and 6 week period so that the total sleep time represents the average total time asleep each night. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Sleep | Baseline, 6 weeks | Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period * Overall sleep quality was measured on a scale of 1=poor to 10=excellent. * Daytime alertness was measured on a scale of 1=not alert to 10=extremely alert. * Daytime fatigue was measured on a scale of 1=not tired to 10=extremely tired. * Daytime functioning was measured on a scale of 1=poor to 10=excellent. |
| Daytime Fatigue | Measured every two weeks (1&2, 3&4, 5&6) | Participants were asked to keep a daily record. * Daytime fatigue was measured on a scale of 1=not tired to 10=extremely tired. The average among weeks 1 and 2, weeks 3 and 4, and weeks 5 and 6 were taken, resulting in 3 averages, where the lowest average is reported as the minimum value of the full range, the middle average is reported as the median, and the highest average is reported as the maximum value of the full range |
| Nighttime Awakenings | Baseline, 6 weeks | Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period |
| Headache Duration | Baseline, 6 weeks | Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period |
| Headache Intensity | Baseline, 6 weeks | Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period * Headache intensity was measured on a scale of 1=not intense to 10=worst headache possible |
| Headache Frequency | Baseline, 6 weeks | Number of days per week in which a participant had a headache. Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period |
Participant flow
Pre-assignment details
A total of 113 subjects were screened. 79 of them were randomized (69.9%). Of the 34 subjects who were not randomized, 8 were screen failures (23.5%), 17 were baseline failures (50.0%), 4 withdrew consent (11.8%), and 5 were lost to follow-up (14.7%).
Participants by arm
| Arm | Count |
|---|---|
| Eszopiclone 3 mg Participants with IHS-II migraine with and/or without aura and with DSM-IV primary insomnia. They were treated for 6 weeks with 3mg eszopiclone, followed by a 2-week runout period. Participants came in for five visits: a screening visit, a randomization visit, a compliance visit, an end-treatment visit, and an exit/early termination visit. | 38 |
| Placebo Participants with IHS-II migraine with and/or without aura and with DSM-IV primary insomnia. They were treated for 6 weeks with placebo, followed by a 2-week runout period. Participants came in for five visits: a screening visit, a randomization visit, a compliance visit, an end-treatment visit, and an exit/early termination visit. | 41 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 |
Baseline characteristics
| Characteristic | Eszopiclone 3 mg | 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 | 38 Participants | 41 Participants | 79 Participants |
| Age, Continuous | 43.8 years STANDARD_DEVIATION 11.1 | 45.0 years STANDARD_DEVIATION 10.5 | 44.4 years STANDARD_DEVIATION 10.8 |
| Race/Ethnicity, Customized Caucasian | 80 percentage of participants | 80 percentage of participants | 80 percentage of participants |
| Race/Ethnicity, Customized Other | 20 percentage of participants | 20 percentage of participants | 20 percentage of participants |
| Region of Enrollment United States | 38 participants | 41 participants | 79 participants |
| Sex: Female, Male Female | 29 Participants | 34 Participants | 63 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 41 |
| other Total, other adverse events | 0 / 38 | 0 / 41 |
| serious Total, serious adverse events | 0 / 38 | 0 / 41 |
Outcome results
Primary
Total Sleep Time
Participants were asked to record an estimated total time asleep on a daily basis. Nightly estimates were averaged over a 2 week period for baseline and 6 week period so that the total sleep time represents the average total time asleep each night.
Time frame: Baseline, 6 weeks
Population: Modified ITT (defined as all participants who took study medication at least 5 days per week for the first 2 weeks of the 6-week treatment period and provided the corresponding diary entries for sleep and headache.)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszoplicone 3mg | Total Sleep Time | Baseline | 5.4 hours | Standard Deviation 0.8 |
| Eszoplicone 3mg | Total Sleep Time | 6 week average | 6.3 hours | Standard Deviation 0.9 |
| Placebo | Total Sleep Time | Baseline | 5.5 hours | Standard Deviation 1 |
| Placebo | Total Sleep Time | 6 week average | 6.1 hours | Standard Deviation 0.8 |
Comparison: The null hypothesis is that there is no difference in the 6 week average total sleep timep-value: 0.33t-test, 2 sided
Secondary
Daytime Fatigue
Participants were asked to keep a daily record. * Daytime fatigue was measured on a scale of 1=not tired to 10=extremely tired. The average among weeks 1 and 2, weeks 3 and 4, and weeks 5 and 6 were taken, resulting in 3 averages, where the lowest average is reported as the minimum value of the full range, the middle average is reported as the median, and the highest average is reported as the maximum value of the full range
Time frame: Measured every two weeks (1&2, 3&4, 5&6)
Population: modified ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eszoplicone 3mg | Daytime Fatigue | 4.3 score on a scale |
| Placebo | Daytime Fatigue | 4.8 score on a scale |
Secondary
Headache Duration
Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period
Time frame: Baseline, 6 weeks
Population: modified ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszoplicone 3mg | Headache Duration | Baseline | 4.0 hours | Standard Deviation 2.3 |
| Eszoplicone 3mg | Headache Duration | 6 weeks | 3.9 hours | Standard Deviation 1.8 |
| Placebo | Headache Duration | Baseline | 3.7 hours | Standard Deviation 2.2 |
| Placebo | Headache Duration | 6 weeks | 3.8 hours | Standard Deviation 2.2 |
Comparison: The null hypothesis is that there is no difference in headache duration between eszopiclone and placebo groups at 6 weeks.p-value: 0.98t-test, 2 sided
Secondary
Headache Frequency
Number of days per week in which a participant had a headache. Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period
Time frame: Baseline, 6 weeks
Population: modified ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszoplicone 3mg | Headache Frequency | Baseline | 2.9 days/week | Standard Deviation 1.2 |
| Eszoplicone 3mg | Headache Frequency | 6 weeks | 2.5 days/week | Standard Deviation 1.3 |
| Placebo | Headache Frequency | Baseline | 3.1 days/week | Standard Deviation 1.2 |
| Placebo | Headache Frequency | 6 weeks | 2.5 days/week | Standard Deviation 1.4 |
Comparison: The null hypothesis is that there is no difference in average days/week between eszopiclone and placebo groups at 6 weeks.p-value: 0.89t-test, 2 sided
Secondary
Headache Intensity
Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period * Headache intensity was measured on a scale of 1=not intense to 10=worst headache possible
Time frame: Baseline, 6 weeks
Population: modified ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszoplicone 3mg | Headache Intensity | Baseline | 5.6 score on a scale | Standard Deviation 2.3 |
| Eszoplicone 3mg | Headache Intensity | 6 weeks | 5.5 score on a scale | Standard Deviation 2 |
| Placebo | Headache Intensity | Baseline | 5.3 score on a scale | Standard Deviation 1.6 |
| Placebo | Headache Intensity | 6 weeks | 5.6 score on a scale | Standard Deviation 1.8 |
Comparison: The null hypothesis is that there is no difference in headache intensity between eszopiclone and placebo groups at 6 weeks.p-value: 0.82t-test, 2 sided
Secondary
Nighttime Awakenings
Participants were asked to keep a daily record. The average among weeks 1 and 2, weeks 3 and 4, and weeks 5 and 6 were taken, resulting in 3 averages, where the lowest average is reported as the minimum value of the full range, the middle average is reported as the median, and the highest average is reported as the maximum value of the full range
Time frame: Measured every two weeks (1&2, 3&4, 5&6)
Population: modified ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Eszoplicone 3mg | Nighttime Awakenings | 1.5 awakenings/night |
| Placebo | Nighttime Awakenings | 2.1 awakenings/night |
Secondary
Nighttime Awakenings
Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period
Time frame: Baseline, 6 weeks
Population: modified ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszoplicone 3mg | Nighttime Awakenings | 6 weeks | 1.5 awakenings/night | Standard Deviation 1.1 |
| Eszoplicone 3mg | Nighttime Awakenings | Baseline | 2.4 awakenings/night | Standard Deviation 1.5 |
| Placebo | Nighttime Awakenings | 6 weeks | 2.2 awakenings/night | Standard Deviation 1.4 |
| Placebo | Nighttime Awakenings | Baseline | 2.7 awakenings/night | Standard Deviation 1.3 |
Comparison: The null hypothesis is that there is no difference between the eszopiclone and placebo groups in the number of awakenings/night at 6 weeks.p-value: 0.03t-test, 2 sided
Secondary
Quality of Sleep
Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period * Overall sleep quality was measured on a scale of 1=poor to 10=excellent. * Daytime alertness was measured on a scale of 1=not alert to 10=extremely alert. * Daytime fatigue was measured on a scale of 1=not tired to 10=extremely tired. * Daytime functioning was measured on a scale of 1=poor to 10=excellent.
Time frame: Baseline, 6 weeks
Population: modified ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eszoplicone 3mg | Quality of Sleep | Overall sleep quality, Baseline | 5.1 score on a scale | Standard Deviation 1.1 |
| Eszoplicone 3mg | Quality of Sleep | Overall sleep quality, 6 weeks | 6.7 score on a scale | Standard Deviation 1.2 |
| Eszoplicone 3mg | Quality of Sleep | Daytime alertness, Baseline | 6.1 score on a scale | Standard Deviation 1.1 |
| Eszoplicone 3mg | Quality of Sleep | Daytime alertness, 6 weeks | 6.9 score on a scale | Standard Deviation 1.3 |
| Eszoplicone 3mg | Quality of Sleep | Daytime fatigue, Baseline | 5.2 score on a scale | Standard Deviation 1.4 |
| Eszoplicone 3mg | Quality of Sleep | Daytime fatigue, 6 weeks | 4.3 score on a scale | Standard Deviation 1.4 |
| Eszoplicone 3mg | Quality of Sleep | Daytime functioning, Baseline | 6.5 score on a scale | Standard Deviation 1.2 |
| Eszoplicone 3mg | Quality of Sleep | Daytime functioning, 6 weeks | 7.0 score on a scale | Standard Deviation 1.3 |
| Placebo | Quality of Sleep | Daytime functioning, 6 weeks | 6.9 score on a scale | Standard Deviation 1.3 |
| Placebo | Quality of Sleep | Overall sleep quality, Baseline | 4.9 score on a scale | Standard Deviation 1.1 |
| Placebo | Quality of Sleep | Daytime fatigue, Baseline | 5.5 score on a scale | Standard Deviation 1.5 |
| Placebo | Quality of Sleep | Overall sleep quality, 6 weeks | 6.2 score on a scale | Standard Deviation 1 |
| Placebo | Quality of Sleep | Daytime functioning, Baseline | 6.3 score on a scale | Standard Deviation 1.5 |
| Placebo | Quality of Sleep | Daytime alertness, Baseline | 6.0 score on a scale | Standard Deviation 1.4 |
| Placebo | Quality of Sleep | Daytime fatigue, 6 weeks | 5.0 score on a scale | Standard Deviation 1.5 |
| Placebo | Quality of Sleep | Daytime alertness, 6 weeks | 6.6 score on a scale | Standard Deviation 1.2 |
Comparison: Null hypothesis is that there is no difference between Eszopiclone and placebo groups in sleep quality averaged over 6 weeks of treatment.p-value: 0.1t-test, 2 sided
Comparison: Null hypothesis is that there is no difference between Eszopiclone and placebo groups in daytime alertness averaged over 6 weeks of treatment.p-value: 0.29t-test, 2 sided
Comparison: Null hypothesis is that there is no difference between Eszopiclone and placebo groups in daytime fatigue averaged over 6 weeks of treatment.p-value: 0.05t-test, 2 sided
Comparison: Null hypothesis is that there is no difference between Eszopiclone and placebo groups in daytime functioning averaged over 6 weeks of treatment.p-value: 0.76t-test, 2 sided