Insomnia, Major Depressive Disorder
Conditions
Keywords
Daridorexant, Clinical Trial, Insomnia, Major depressive disorder, Polysomnography, Insomnia Severity Index
Brief summary
The goal of this clinical trial is to evaluate the efficacy and safety of Daridorexant in major depressive disorder (MDD) patients with comorbid insomnia. The main questions to answer are: 1. Does Daridorexant improve the severity of insomnia as measured by the Insomnia Severity Index (ISI)? 2. Does Daridorexant have an impact on depressive symptoms? In order to address these questions, researchers will compare Daridorexant with a placebo to evaluate its impact on both insomnia and MDD-related symptoms. Participants will: * Receive Daridorexant or placebo for a duration of three months * Complete a Sleep Diary and other questionnaires assessing sleep and depressive symptoms. * Undergo polysomnography to obtain objective measurements of sleep parameters.
Detailed description
Insomnia is an extensively studied condition, yet its interactions with major depressive disorder (MDD) remain insufficiently understood. This study aims to evaluate the efficacy and safety of Daridorexant in MDD patients with comorbid insomnia. The primary objective is to determine whether Daridorexant improves the severity of insomnia, as measured by the Insomnia Severity Index (ISI), while assessing its impact on depressive symptoms will be considered the secondary objective. A prospective, double-blind, randomized, multicenter, placebo-controlled trial will be conducted in major depressive disorder outpatient clinic of the psychiatry department. Eligible patients will be randomized to Daridorexant versus placebo. Neither participants nor investigators will be aware of the treatment allocation. Standardized procedures for blinding and emergency unblinding will be implemented across all centers. The main outcome will be the improvement of Insomnia Severity Index (ISI) but additionally total sleep time, wake after sleep onset time, sleep latency and sleep efficiency will be measured. Data collection will include the Pittsburgh Sleep Quality Index (PSQI), depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), suicidal thoughts measured by the MINI-Neuropsychiatry Scale, quality of life measured by EuroQol, Dysfunctional Beliefs and Attitudes about Sleep (DBAS) and Polysomnography at baseline and 3 months. The study aims to demonstrate improvements in patient's subjective experience of insomnia, and additionally objective quantifiable improvements of objective sleep measurements via polysomnography, without an associated increase in depressive symptoms.
Interventions
oral taking of Daridorexant 50mg/daily at bedtime, within 30 minutes of going to bed and at least 8-9 hours before planned wake time. Treatment duration: 12 weeks (3 months).
DRUGPlacebo
Orally, once daily at bedtime, within 30 minutes of going to bed and at least 8-9 hours before planned wake time.
Sponsors
Institut d'Investigació Biomèdica de Bellvitge
Idorsia Pharmaceuticals Ltd.
Hospital Universitari de Bellvitge
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age Range: 18-99 years old. * Patients with a current major depressive episode according to DSM-5, in a stable phase (defined as at least 4 weeks without significant changes in antidepressant treatment and no psychiatric hospitalizations in the previous 8 weeks) and with moderate or greater severity, as indicated by a total score of * 20 on the Montgomery-Åsberg Depression Rating Scale (MADRS). * Insomnia disorder confirmed according to DSM-5 * Insomnia Severity: Insomnia Severity Index (ISI) score = o \>15. * Medication Stability defined by : * Stable doses of antidepressants, mood stabilizers, or antipsychotics for at least 1 month prior to baseline (T0). * Melatonin, Benzodiacepines, sedative antidepressants or sedative antipsychotics use for insomnia should follow a wash out protocol described below. * Informed Consent: Ability and willingness to provide written informed consent. * Acceptance of Protocol Requirements: Agreement to adhere to all scheduled visits, treatment plans, and study procedures.
Exclusion criteria
* Other Current Psychiatric Disorders: Any current psychiatric disorder other than major depressive disorder (e.g., active psychotic disorders, mania, hypomania, acute schizophrenia, schizoaffective disorder). * Use of Non-Permitted Sleep Medications: Concurrent use of melatonin, benzodiazepines, sedative antidepressants or sedative antipsychotics use for insomnia not allowed by the protocol and unwillingness to follow the slow- taper schedule constitutes an exclusion criterion. * No concurrent sleep medications at least 30 days prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insomnia Severity Index (ISI) | ISI will be administered to all patients at baseline, and at months 1 and 3. | The Insomnia Severity Index is a widely used, self-reported questionnaire designed to assess the nature, severity, and impact of insomnia symptoms. Each item is rated on a 5-point Likert scale from 0 to 4. The total score ranges from 0 to 28, with higher scores indicating greater insomnia severity. According to the results insomnia will be classified as follows: 0-7: absence of clinical insomnia; 8-14: subclinical insomnia; 15-21: clinical insomnia; 22-28: severe insomnia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Efficiency (polysomnography) | Polysomnography will be performed at baseline and at month 3. | •Sleep Efficiency (%): Total Sleep Time (minutes) / time in bed (minutes). |
| Total Sleep Time (Polysomnography) | PSG will be performed at baseline and at month 3. | Total Sleep Time (TST): measured in minutes. |
| Wake After Sleep Onset (polysomnography) | Polysomnography will be performed at baseline and at month 3. | Total number of minutes that a patient is awake after having initially fallen asleep. |
| Arousal Index (polysomnography) | Polysomnography will be performed at baseline and at month 3. | Number of arousals per hour of sleep. |
| Cumulative time spent under 90% oxygen saturation (polysomnography) | Polysomnography will be performed at baseline and at month 3. | \[time under 90% oxygen saturation (min) / total sleep time (min)\] · 100 (%) |
| Periodic Leg Movement Index (Polysomnography) | Polysomngraphy will be performed at baseline and at month 3. | number of leg movements per hour of sleep. |
| Apnea-Hypopnea Index (polysomnography) | Polysomnography will be performed at baseline and at month 3. | number of apneas and hypopneas per hour of sleep. |
| Pittsburg Sleep Quality Index (PSQI) | PSQI will be administered to all patients at baseline, and at months 1 and 3. | Each item is rated on a 4-point Likert scale from 0 to 3. The total score varies between 0 and 21, with higher scores indicating greater difficulties with sleep. |
| Dysfunctional Beliefs and Attitudes about Sleep (DBAS) | The DBAS will be administered to all patients at baseline, and at months 1 and 3. | Each item is rated on a 5-point Likert scale from 1 to 5. The total score ranges from 30 to 150, with lower scores indicating a greater presence of dysfunctional beliefs and attitudes about sleep. |
| Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) | The IDSIQ will be administered daily to all patients from baseline through month 3. | The IDSIQ is a patient-reported outcome measure assessing daytime functioning impairments associated with insomnia. It comprises 14 items, each rated on a 0-10 scale. Items are summed to obtain a total score (range: 0-140). Interpretation: Higher scores indicate greater daytime impairment related to insomnia. |
| Montgomery-Åsberg Depression Rating Scale (MADRS) | MADRS will be administered to all patients at baseline, and at months 1 and 3. | The assessment should be based on a clinical interview that ranges from general questions about symptoms to more detailed questions that allow for a precise evaluation of severity. The evaluator must decide whether the assessment corresponds to the responses defined at the levels of the scale (0, 2, 4, 6) or to those between them (1, 3, 5). The total score ranges from 0 to 60. Interpretation: No depression (0-6); mild (7-19); moderate (20-34); severe (35-60). |
| Suicidal Scale of the Mini-International Neuropsychiatric Interview (MINI) | Will be administered to all patients at baseline and at months 1 and 3. | Only the suicide item of the MINI will be administered. Each item is scored dichotomously (Yes/No). Points are assigned to "Yes" responses and summed to yield a total score: Wish to be dead: 1 point Self-harm desire: 2 points Suicidal ideation: 6 points Suicide plan: 10 points Suicide attempt (past month): 10 points Lifetime suicide attempt: 4 points Total score range: 0-33 Risk categories: 0: No risk 1-5: Low risk 6-9: Moderate risk ≥10: High risk |
| EuroQol-5D-5L | Will be administered at baseline and at month 3. | The EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each rated on ordered levels. Each item is rated on a 5-point Likert scale from 1 to 5. The total score ranges from 5 to 25, with higher scores indicating poorer health status. The instrument also includes a visual analogue scale, where pacients rate their overall health from 0 (worst imaginable health) to 100 (best imaginable health). |
| Sleep onset (Sleep diary) | The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit. | Time in minutes between attempting to fall asleep and the onset of sleep. |
| Sleep latency (Sleep diary) | The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit. | Time interval between attempting to initiate sleep (lights-off) and the onset of sleep, as measured in minutes. |
| Wakefulness after sleep onset (sleep diary) | The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit. | Total duration of time spent awake after initial sleep onset and before final awakening, as measured in minutes. |
| Total sleep time (sleep diary) | The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit. | Total Sleep Time (TST): measured in minutes. |
| Total time spent in bed (sleep diary) | The sleep diary will be administered at baseline and at months 1 and 3, for seven consecutive days prior to each visit. | Time spent by the patient at bed, as measured in minutes. |
Countries
Spain
Contacts
CONTACTSara Lakis Granell, MD
Outcome results
None listed