Bipolar Disorder, Insomnia
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy of suvorexant, added to existing medications, for treatment-resistant insomnia in individuals with bipolar disorder. The investigators hypothesize that participants receiving suvorexant for one week will experience significantly greater improvement in sleep duration compared to participants receiving placebo.
Detailed description
Participants will be randomized to receive double-blind suvorexant or placebo for one week, after which all participants will receive open treatment with suvorexant for three months.
Interventions
DRUGSuvorexant
DRUGPlacebo
Sponsors
Merck Sharp & Dohme LLC
Stanford 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 No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for bipolar I disorder (296.70), bipolar II disorder (296.89), or bipolar disorder not otherwise specified (296.80), with concurrent insomnia related to bipolar disorder (307.42). 2. Currently taking ≥ 1 prescription psychotropic medication (hypnotic agents, anxiolytics, atypical antipsychotics, mood stabilizers, and/or antidepressants) for management of bipolar disorder. 3. Subjective total sleep time (sTST) \< 6 hours on ≥ 1 night during the prior week.
Exclusion criteria
1. Current hypo/manic symptoms, as evidenced by the Young Mania Rating Scale (YMRS) total score ≥ 12. 2. Current (past 6 months) alcohol or substance use disorder. 3. Current psychosis. 4. Patients who are actively suicidal or evaluated as being a high suicide risk. 5. Women who are currently pregnant or breastfeeding. 6. Clinically significant abnormalities on baseline laboratory tests (comprehensive metabolic panel, fasting lipid panel, Complete Blood Count (CBC) with differential, thyroid stimulating hormone). 7. Presence of any unstable and/or potentially confounding neurological and/or medical disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subjective Total Sleep Time - Acute | baseline and week 1 of double-blind, placebo-controlled phase | Measured by self-report electronic sleep diary. Change is calculated as week 1 value minus week 0 value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Objective Total Sleep Time - Acute | baseline and week 1 of double-blind, placebo-controlled phase | Measured by actigraphy. Change is calculated as week 1 value minus week 0 value. |
| Subjective Total Sleep Time - Subchronic | week 1 and month 3 of open treatment phase | Measured by self-report electronic sleep diary. Change is calculated as the month 3 value minus the week 1 value |
| Change in Objective Total Sleep Time - Subchronic | week 1 and month 3 of open treatment phase | Measured by actigraphy. Change is measured as the month 3 value minus the week 1 value. |
Countries
United States
Participant flow
Pre-assignment details
61 participants consented, 48 participants were randomized to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Suvorexant Participants receive double-blind suvorexant for one week, dosed at 10mg every bedtime for the first 3 nights, then increased to 20mg every bedtime for the last 4 nights. Following the double-blind phase, participants receive open-label suvorexant for 3 months, dosed at 10mg every bedtime for the first 3 nights, then increased to 20mg every bedtime for the remainder of 3 months. | 19 |
| Placebo Participants receive double-blind placebo to match suvorexant for one week. Following the double-blind phase, participants receive open-label suvorexant for 3 months, dosed at 10mg every bedtime for the first 3 nights, then increased to 20mg every bedtime for the remainder of 3 months. | 17 |
| Total | 36 |
Baseline characteristics
| Characteristic | Suvorexant | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 52.84 years STANDARD_DEVIATION 14.792 | 44.53 years STANDARD_DEVIATION 14.841 | 48.92 years STANDARD_DEVIATION 15.197 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Multi/Other | 5 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 9 Participants | 21 Participants |
| Region of Enrollment United States | 19 Participants | 17 Participants | 36 Participants |
| Sex: Female, Male Female | 14 Participants | 11 Participants | 25 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 25 | 0 / 46 |
| other Total, other adverse events | 1 / 23 | 1 / 25 | 3 / 46 |
| serious Total, serious adverse events | 0 / 23 | 1 / 25 | 0 / 46 |
Outcome results
Primary
Change in Subjective Total Sleep Time - Acute
Measured by self-report electronic sleep diary. Change is calculated as week 1 value minus week 0 value.
Time frame: baseline and week 1 of double-blind, placebo-controlled phase
Population: Participants who received the allocated intervention and with data at all time points are included in the analysis. This outcome was assessed in the double-blind groups only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant (Double-blind) | Change in Subjective Total Sleep Time - Acute | week 0 | 7.04 hours | Standard Deviation 1.16 |
| Suvorexant (Double-blind) | Change in Subjective Total Sleep Time - Acute | week 1 | 7.53 hours | Standard Deviation 1.43 |
| Suvorexant (Double-blind) | Change in Subjective Total Sleep Time - Acute | change at week 1 | 0.49 hours | Standard Deviation 1.03 |
| Placebo (Double-blind) | Change in Subjective Total Sleep Time - Acute | week 0 | 7.03 hours | Standard Deviation 0.55 |
| Placebo (Double-blind) | Change in Subjective Total Sleep Time - Acute | week 1 | 7.20 hours | Standard Deviation 0.68 |
| Placebo (Double-blind) | Change in Subjective Total Sleep Time - Acute | change at week 1 | 0.17 hours | Standard Deviation 0.9 |
Comparison: Within group change at week 1 - suvorexant (double-blind)p-value: 0.1Paired 2-sided t-test
Comparison: Within group change at week 1- placebo (double-blind) groupp-value: 0.57Paired 2-sided t-test
Comparison: Between group change at week 1p-value: 0.44Unpaired 2-sided t-test
Secondary
Change in Objective Total Sleep Time - Acute
Measured by actigraphy. Change is calculated as week 1 value minus week 0 value.
Time frame: baseline and week 1 of double-blind, placebo-controlled phase
Population: Participants who received the allocated intervention and with data at all time points are included in the analysis. This outcome was assessed in the double-blind groups only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant (Double-blind) | Change in Objective Total Sleep Time - Acute | week 0 | 6.46 hours | Standard Deviation 2.06 |
| Suvorexant (Double-blind) | Change in Objective Total Sleep Time - Acute | week 1 | 7.20 hours | Standard Deviation 2.6 |
| Suvorexant (Double-blind) | Change in Objective Total Sleep Time - Acute | change at week 1 | 0.74 hours | Standard Deviation 1.17 |
| Placebo (Double-blind) | Change in Objective Total Sleep Time - Acute | week 0 | 9.50 hours | Standard Deviation 4.64 |
| Placebo (Double-blind) | Change in Objective Total Sleep Time - Acute | week 1 | 10.10 hours | Standard Deviation 4.1 |
| Placebo (Double-blind) | Change in Objective Total Sleep Time - Acute | change at week 1 | 0.61 hours | Standard Deviation 3.15 |
Comparison: Within group change at week 1 - suvorexant (double-blind)p-value: 0.035Paired 2-sided t-test
Comparison: Within group change at week 1- placebo (double-blind) groupp-value: 0.55Paired 2-sided t-test
Comparison: Between group change at week 1p-value: 0.89Paired 2-sided t-test
Secondary
Change in Objective Total Sleep Time - Subchronic
Measured by actigraphy. Change is measured as the month 3 value minus the week 1 value.
Time frame: week 1 and month 3 of open treatment phase
Population: Participants who received the allocated intervention and with data at all time points are included in the analysis. Month 3 data were collected using last observation carried forward method (LOCF). This outcome was assessed in the open-label group only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant (Double-blind) | Change in Objective Total Sleep Time - Subchronic | week 1 | 8.69 hours | Standard Deviation 3.44 |
| Suvorexant (Double-blind) | Change in Objective Total Sleep Time - Subchronic | month 3 | 9.58 hours | Standard Deviation 4.56 |
| Suvorexant (Double-blind) | Change in Objective Total Sleep Time - Subchronic | change at month 3 | 0.88 hours | Standard Deviation 3.82 |
Comparison: Within group change at month 3 - suvorexant (open-label)p-value: 0.28Paired 2-sided t-test
Secondary
Subjective Total Sleep Time - Subchronic
Measured by self-report electronic sleep diary. Change is calculated as the month 3 value minus the week 1 value
Time frame: week 1 and month 3 of open treatment phase
Population: Participants who received the allocated intervention and with data at all time points are included in the analysis. Month 3 data were collected using last observation carried forward method (LOCF). This outcome was assessed in the open-label group only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant (Double-blind) | Subjective Total Sleep Time - Subchronic | week 1 | 7.24 hours | Standard Deviation 1.32 |
| Suvorexant (Double-blind) | Subjective Total Sleep Time - Subchronic | month 3 | 7.25 hours | Standard Deviation 1.56 |
| Suvorexant (Double-blind) | Subjective Total Sleep Time - Subchronic | change at month 3 | 0.01 hours | Standard Deviation 1.29 |
Comparison: Within group change at month 3 - suvorexant (open-label)p-value: 0.97Paired 2-sided t-test