Treatment of Insomnia in Migraineurs | NCT00812214

Treatment of Insomnia in Migraineurs | NCT00812214 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Eszopiclone (Lunesta) 3mg	Experimental	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.	Drug: eszopiclone
Placebo	Placebo Comparator	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.	Drug: placebo

Name	Type	Description	Arm Group Labels	Other Names
eszopiclone	Drug	3 mg tablet every night at bedtime	Eszopiclone (Lunesta) 3mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Baseline, 6 weeks

Secondary Outcomes

Measure	Description	Time Frame
Nighttime Awakenings	Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period	Baseline, 6 weeks
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

Name	Affiliation	Role
Egilius LH Spierings, M.D., Ph.D.	MedVadis Research Corporation	Principal Investigator

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25323219	Result	Spierings EL, McAllister PJ, Bilchik TR. Efficacy of treatment of insomnia in migraineurs with eszopiclone (Lunesta(R)) and its effect on total sleep time, headache frequency, and daytime functioning: A randomized, double-blind, placebo-controlled, parallel-group, pilot study. Cranio. 2015 Apr;33(2):115-21. doi: 10.1179/0886963414Z.00000000084. Epub 2014 Oct 16.

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00038 subjects FG00141 subjects
COMPLETED		FG00035 subjects FG00140 subjects
NOT COMPLETED		FG0003 subjects FG0011 subjects

Type	Comment	Reasons
Lost to Follow-up		FG0003 subjects FG0011 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.)

Posted

Mean

Standard Deviation

hours

Baseline, 6 weeks

ID	Title	Description
OG000	Eszoplicone 3mg	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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Eszopiclone 3mg	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.

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Egilius L.H. Spierings, M.D., Ph.D.	MedVadis Research Corporation	617-744-1310		Spierings@MedVadis.com

Condition Browse Module

ID	Term
D007319	Sleep Initiation and Maintenance Disorders
D008881	Migraine Disorders

ID	Term
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases

Intervention Browse Module

ID	Term
D000069582	Eszopiclone

ID	Term
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines

Title

Denominators

Categories

- ParticipantsBG00038
- ParticipantsBG00141
- ParticipantsBG00279

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years	BG00038 BG00141 BG00279
>=65 years	BG0000 BG0010 BG0020

Race/Ethnicity, Customized

Baseline data only available for mITT participants (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)

Number

percentage of participants

Title

Denominators

Categories

Caucasian

- ParticipantsBG00035
- ParticipantsBG00140
- ParticipantsBG00275

Title	Measurements
	BG00080 BG00180 BG00280

Other

- ParticipantsBG00035
- ParticipantsBG00140
- ParticipantsBG00275

Title	Measurements
	BG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference in the 6 week average total sleep time	t-test, 2 sided	two-tailed student's t-test for independent samples	0.33														Superiority	For the purpose of the power calculation, it was assumed that the difference in total sleep time between the treatment groups is 40 minutes, with a standard deviation of 60. The pilot nature of the study allowed the use of alpha = 0.05 and beta = 0.2, with two-sided comparison, generating a required sample size of 37 subjects per arm.

Secondary

Nighttime Awakenings

Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period

modified ITT

Posted

Mean

Standard Deviation

awakenings/night

Baseline, 6 weeks

ID	Title	Description
OG000	Eszopiclone 3mg	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.
OG001	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.

Units	Counts
Participants	OG00035 OG00140

Title

Denominators

Categories

Baseline

Title	Measurements
	OG0002.4± 1.5 OG0012.7± 1.3

6 weeks

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference between the eszopiclone and placebo groups in the number of awakenings/night at 6 weeks.	t-test, 2 sided		0.03														Superiority

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

modified ITT

Posted

Median

Full Range

awakenings/night

Measured every two weeks (1&2, 3&4, 5&6)

ID	Title	Description
OG000	Eszopiclone 3mg	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.
OG001	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.

Units	Counts
Participants	OG00035 OG00140

Title

Denominators

Categories

Title	Measurements
	OG0001.5(1.5 to 1.6) OG0012.1(2.1 to 2.2)

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.

modified ITT

Posted

Mean

Standard Deviation

score on a scale

Baseline, 6 weeks

ID	Title	Description
OG000	Eszopiclone 3mg	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.
OG001	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.

Units	Counts
Participants	OG00035 OG00140

Title

Denominators

Categories

Overall sleep quality, Baseline

Title	Measurements
	OG0005.1± 1.1 OG0014.9± 1.1

Overall sleep quality, 6 weeks

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis is that there is no difference between Eszopiclone and placebo groups in sleep quality averaged over 6 weeks of treatment.	t-test, 2 sided		0.1														Superiority
OG000 OG001	Null hypothesis is that there is no difference between Eszopiclone and placebo groups in daytime alertness averaged over 6 weeks of treatment.

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.

modified ITT

Posted

Median

Full Range

score on a scale

Measured every two weeks (1&2, 3&4, 5&6)

ID	Title	Description
OG000	Eszopiclone 3mg	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.
OG001	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.

Units	Counts
Participants	OG00035 OG00140

Title

Denominators

Categories

Title	Measurements
	OG0004.3(4.2 to 4.4) OG0014.8(4.8 to 5.2)

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

modified ITT

Posted

Mean

Standard Deviation

days/week

Baseline, 6 weeks

ID	Title	Description
OG000	Eszopiclone 3mg	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.
OG001	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.

Units	Counts
Participants	OG00035 OG00140

Title

Denominators

Categories

Baseline

Title	Measurements
	OG0002.9± 1.2 OG0013.1± 1.2

6 weeks

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference in average days/week between eszopiclone and placebo groups at 6 weeks.	t-test, 2 sided		0.89														Superiority

Secondary

Headache Duration

Participants were asked to keep a daily record. 6 week data were averaged over the 6 week period

modified ITT

Posted

Mean

Standard Deviation

hours

Baseline, 6 weeks

ID	Title	Description
OG000	Eszopiclone 3mg	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.
OG001	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.

Units	Counts
Participants	OG00035 OG00140

Title

Denominators

Categories

Baseline

Title	Measurements
	OG0004.0± 2.3 OG0013.7± 2.2

6 weeks

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference in headache duration between eszopiclone and placebo groups at 6 weeks.	t-test, 2 sided		0.98														Superiority

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

modified ITT

Posted

Mean

Standard Deviation

score on a scale

Baseline, 6 weeks

ID	Title	Description
OG000	Eszopiclone 3mg	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.
OG001	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.

Units	Counts
Participants	OG00035 OG00140

Title

Denominators

Categories

Baseline

Title	Measurements
	OG0005.6± 2.3 OG0015.3± 1.6

6 weeks

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis is that there is no difference in headache intensity between eszopiclone and placebo groups at 6 weeks.	t-test, 2 sided		0.82														Superiority