Chronic Insomnia
Conditions
Brief summary
This proposal will assess risks for transition from therapeutic hypnotic use to abuse in people with insomnia. The investigators will study a hypothesized at-risk sub-population, insomniacs with hyperarousal, and compare two hypnotics, a drug with mood effects, eszopiclone, versus one without mood effects, zolpidem.
Detailed description
Persons with DSM-V diagnosed insomnia disorder, aged 18-65 yrs, with no other sleep disorders, unstable medical or psychiatric diseases or drug dependency will be entered to the trial. Following a screening NPSG and MSLT, participants will be randomized to zolpidem XR 12.5 mg (n=60), eszopiclone 3 mg (n=60), or placebo (n=50) nightly for 6 months. After 6 months of nightly use, over a 2-week choice period, they were instructed to discontinue hypnotic use, but if necessary, to self-administer either 1, 2, or 3 capsules of their assigned blinded medication (zolpidem XR 6.25 mg, 6.25 mg, placebo; eszopiclone 2 mg, 1 mg, placebo as capsules 1, 2 and 3 respectively; or 3 placebos). Nightly sleep at home will be recorded by actigraphy for one week after the screening NPSG and MSLT and before treatment is initiated and actigraphy again during the two week discontinuation.
Interventions
DRUGplacebo
six months of nightly placebo
DRUGZolpidem CR
six months of nightly zolpidem
DRUGEszopiclone
Sponsors
Henry Ford Health System
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
* DSM-5 diagnosis of insomnia
Exclusion criteria
* acute or unstable medical disease, * current or past history of psychiatric disease, alcoholism or drug abuse, and other primary sleep disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Capsules Taken During Discontinuation From Either Active Drug vs Placebo Over a Two Week Period | total number of capsules chosen in week 1 and week 2 of the discontinuation period | instruction to stop nightly hypnotic use over a two-week discontinuation period with option to choose of 1, 2, 3 capsules, if necessary |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Time Asleep Over Time in Bed During the Two-week Discontinuation Period | mean nightly sleep efficiency during week 1 and week 2 of the discontinuation period | comparing the three treatment arms for nightly hypnotic efficacy using actigraphic determined sleep efficiency over the two week discontinuation period |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Intervention: Six months of nightly placebo
placebo | 14 |
| Zolpidem CR Intervention: Six months of zolpidem cr 12.5 mg nightly use
Zolpidem CR | 11 |
| Eszopiclone Intervention: Six months of eszopiclone 3 mg nightly use
Eszopiclone | 16 |
| Total | 41 |
Baseline characteristics
| Characteristic | Eszopiclone | Total | Placebo | Zolpidem CR |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 41 Participants | 14 Participants | 11 Participants |
| Age, Continuous | 41.1 years STANDARD_DEVIATION 12.6 | 43.5 years STANDARD_DEVIATION 11.1 | 47.2 years STANDARD_DEVIATION 9.1 | 42.5 years STANDARD_DEVIATION 10.8 |
| Average daytime sleep latency in min | 11.7 minutes STANDARD_DEVIATION 5.1 | 11.5 minutes STANDARD_DEVIATION 5.4 | 11.1 minutes STANDARD_DEVIATION 5.1 | 11.9 minutes STANDARD_DEVIATION 6.5 |
| Baseline PSG defined sleep efficiency | 78.7 percent sleep per 8 hrs STANDARD_DEVIATION 13 | 76.7 percent sleep per 8 hrs STANDARD_DEVIATION 13.3 | 75.2 percent sleep per 8 hrs STANDARD_DEVIATION 15.9 | 75.7 percent sleep per 8 hrs STANDARD_DEVIATION 10.5 |
| Race (NIH/OMB) Count of Participants American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Count of Participants Asian | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Count of Participants Black or African American | 8 Participants | 19 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) Count of Participants More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Count of Participants Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Count of Participants Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Count of Participants White | 8 Participants | 19 Participants | 4 Participants | 7 Participants |
| Region of Enrollment United States | 16 participants | 41 participants | 14 participants | 11 participants |
| Sex: Female, Male Female | 14 Participants | 36 Participants | 12 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 11 | 0 / 16 |
| other Total, other adverse events | 0 / 14 | 0 / 11 | 0 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 11 | 0 / 16 |
Outcome results
Primary
Total Number of Capsules Taken During Discontinuation From Either Active Drug vs Placebo Over a Two Week Period
instruction to stop nightly hypnotic use over a two-week discontinuation period with option to choose of 1, 2, 3 capsules, if necessary
Time frame: total number of capsules chosen in week 1 and week 2 of the discontinuation period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Number of Capsules Taken During Discontinuation From Either Active Drug vs Placebo Over a Two Week Period | 0.43 Total number capsules chosen | Standard Deviation 1.6 |
| Zolpidem CR | Total Number of Capsules Taken During Discontinuation From Either Active Drug vs Placebo Over a Two Week Period | 2.6 Total number capsules chosen | Standard Deviation 4.5 |
| Eszopiclone | Total Number of Capsules Taken During Discontinuation From Either Active Drug vs Placebo Over a Two Week Period | 6.3 Total number capsules chosen | Standard Deviation 10.5 |
p-value: =0.05ANOVA
Secondary
Percent of Time Asleep Over Time in Bed During the Two-week Discontinuation Period
comparing the three treatment arms for nightly hypnotic efficacy using actigraphic determined sleep efficiency over the two week discontinuation period
Time frame: mean nightly sleep efficiency during week 1 and week 2 of the discontinuation period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent of Time Asleep Over Time in Bed During the Two-week Discontinuation Period | 81.9 % sleep time/bedtime | Standard Deviation 8.1 |
| Zolpidem CR | Percent of Time Asleep Over Time in Bed During the Two-week Discontinuation Period | 84.4 % sleep time/bedtime | Standard Deviation 5.1 |
| Eszopiclone | Percent of Time Asleep Over Time in Bed During the Two-week Discontinuation Period | 83.0 % sleep time/bedtime | Standard Deviation 4.9 |
p-value: =0.643ANOVA