Asthma, Insomnia
Conditions
Brief summary
This trial will test the efficacy and safety of ramelteon, a selective melatonin agonist, on patients with insomnia comorbid with asthma.
Detailed description
Subjects with insomnia comorbid with asthma will be randomized to placebo or ramelteon at night for 6 weeks.
Interventions
DRUGRamelteon
melatonin agonist
Sponsors
Takeda
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Ages 18 - 60 with both insomnia and asthma. * Insomnia: * a complaint of difficulty initiating sleep, difficulty maintaining sleep, or waking up too early or sleep that is chronically nonrestorative or poor in quality, * the sleep difficulty occurs despite adequate opportunity and circumstances for sleep, and * at least one form of daytime impairment related to the nighttime sleep difficulty must be present. The sleep complaint should be present on most days for at least 3 months. * Additional inclusion criteria include: a subjective TST \<6.5 h and a subjective SL \> 45 min per night; a mean LPS \>20 min over 2 consecutive nights by polysomnography (neither night could have been \<15 min); a habitual bedtime between 10 PM and 1 AM; and ISI score \> 10 (based on 0-4 scale). LPS is defined as amount of time to the first 10 minutes of continuous sleep. * Asthma will be diagnosed based on suggestive clinical history and either * airway hyperresponsiveness indicated by a 20% or greater decrease in FEV1 in response to inhalation of methacholine at 8 mg/mL or less * bronchodilator-responsive expiratory airflow limitation (if FEV1 \< 70% of predicted value or \< 1.5 L, improving ≥200 mL and 12% in response to 180 µg of albuterol aerosol). In addition to the above criteria, patients should have well-controlled asthma as evidenced by ACQ score \< 1.5.
Exclusion criteria
* Primary sleep pathology, other than insomnia as assessed by sleep history and confirmed by polysomnography to exclude significant sleep apnea (RDI \> 15), periodic leg movements (movement arousal index \> 15), REM behavior disorder; or circadian sleep-wake disorders * History of cognitive or other neurological disorders; * History of DSM-IV criteria for any major psychiatric disorder, including mania or alcohol or substance abuse; * Depressive symptoms as assessed by the CES-D. Subjects with a score of 22 or greater indicates that the person may be suffering from a major depression and therefore, will be referred to their physician; * Unstable or serious medical conditions; * Current, or use within the past month, of psychoactive, hypnotic, stimulant or analgesic medications (except occasionally); * Shift work or other types of self imposed irregular sleep schedules; * Obesity (BMI \> 35 Kg/m2); or * Pregnancy or desire to become pregnant during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pittsburgh Sleep Quality Index | baseline and post-treatment (at end of 5 weeks) | The change in ISI and PSQI from baseline to end of study will be compared between the two groups. PSQI has a score range of 0-21, with lower the number being less sleep disturbances ISI has a score range of 0-28, with lower score meaning less insomnia symptoms |
| Insomnia Severity Index | 5 weeks | The change in ISI and PSQI from baseline to end of study will be compared between the two groups. PSQI has a score range of 0-21, with lower the number being less sleep disturbances ISI has a score range of 0-28, with lower score meaning less insomnia symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daytime Sleepiness (Epworth Sleepiness Scale) | baseline and post-treatment (at end of 5 weeks) | Score of 0-24, with 24 being the most sleepy |
| Daytime Performance (Digit Symbol Substitution Test) | baseline and post-treatment (at end of 5 weeks) | DSST tests the number of correct digit-symbol pairs that an individual can identify within an allotted period (60-90 sec). It test memory and concentration, among other parameters. DSST score can range from 0-125, with 125 being the most number correct during the allotted time period. |
| Daytime Lung Function (Peak Flow Monitoring) in Liter/Min | baseline and during treatment period (during 5th week) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon Participants with insomnia and asthma are randomized to Ramelteon 8mg and sleep hygiene for 5 weeks or to placebo and sleep hygiene for 5 weeks. Ramelteon or placebo to be taken within 30 minutes before | 2 |
| Placebo Participants with insomnia and asthma are randomized to Ramelteon 8mg and sleep hygiene for 5 weeks or to placebo and sleep hygiene for 5 weeks. Ramelteon or placebo to be taken within 30 minutes before | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Placebo | Ramelteon | 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 | 2 Participants | 3 Participants |
| Age Continuous | 38 years | 34.5 years STANDARD_DEVIATION 9.2 | 35.6 years STANDARD_DEVIATION 6.8 |
| Region of Enrollment United States | 1 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Insomnia Severity Index
The change in ISI and PSQI from baseline to end of study will be compared between the two groups. PSQI has a score range of 0-21, with lower the number being less sleep disturbances ISI has a score range of 0-28, with lower score meaning less insomnia symptoms
Time frame: 5 weeks
Population: The 2 subjects in the Ramelteon group completed the study. The 1 subject in the placebo group did not complete the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Insomnia Severity Index | -6.5 units on a scale | Standard Deviation 6.36 |
Primary
Pittsburgh Sleep Quality Index
The change in ISI and PSQI from baseline to end of study will be compared between the two groups. PSQI has a score range of 0-21, with lower the number being less sleep disturbances ISI has a score range of 0-28, with lower score meaning less insomnia symptoms
Time frame: baseline and post-treatment (at end of 5 weeks)
Population: The 2 subjects in the Ramelteon group completed the study. The 1 subject in the placebo group did not complete the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Pittsburgh Sleep Quality Index | 2 units on a scale | Standard Deviation 0 |
Secondary
Daytime Lung Function (Peak Flow Monitoring) in Liter/Min
Time frame: baseline and during treatment period (during 5th week)
Population: This measure was added during the study and no subjects completed the measure.
Secondary
Daytime Performance (Digit Symbol Substitution Test)
DSST tests the number of correct digit-symbol pairs that an individual can identify within an allotted period (60-90 sec). It test memory and concentration, among other parameters. DSST score can range from 0-125, with 125 being the most number correct during the allotted time period.
Time frame: baseline and post-treatment (at end of 5 weeks)
Population: The 2 subjects in the Ramelteon group completed the study. The 1 subject in the placebo group did not complete the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Daytime Performance (Digit Symbol Substitution Test) | 8 Number correct | Standard Deviation 1.4 |
Secondary
Daytime Sleepiness (Epworth Sleepiness Scale)
Score of 0-24, with 24 being the most sleepy
Time frame: baseline and post-treatment (at end of 5 weeks)
Population: The 2 subjects in the Ramelteon group completed the study. The 1 subject in the placebo group did not complete the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Daytime Sleepiness (Epworth Sleepiness Scale) | 3.5 units on a scale | Standard Deviation 0.7 |