Clinical trial NCT06779149: Efficacy of CBT-I and Lemborexant Medication for Different Subtypes of Chronic Insomnia
Official title: Efficacy of CBT-I and Lemborexant Medication for Different Subtypes of Chronic Insomnia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Insomnia Disorder
Keywords: Insomnia
Cognitive behavioral therapy for insomnia
Lemborexant
Insomnia phenotypes
Objective short sleep duration
Lead sponsor: Laval University
Sponsor class: OTHER
Collaborators: name: Toronto Metropolitan University
name: The Royal Ottawa Mental Health Centre
First posted: 2025-01-16
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary aims of this study is to contrast the effectiveness of CBT-I and pharmacotherapy (lemborexant) compared to placebo on sleep and mental health outcomes in people with insomnia disorder and anxiety/depressive symptoms. In addition, the study will evaluate whether insomnia phenotypes (i.e., +/- 6hrs of sleep) at baseline moderate the effectiveness of the intervention on both sleep and mental health outcomes.

Detailed description: Participants meeting study criteria will be randomized to one of three conditions (1:1:1) involving a 8-week treatment protocol (6 consultations over an 8-week period): 1) CBT-I, 2) an active hypnotic medication (lemborexant, 5-10 mg at bedtime) or 3) a placebo medication. A stratified-based variable block randomization schedule will be used to assign eligible patients to study arms once they have completed baseline measures. Stratification will be based on objective (EEG-defined) sleep duration (\< 6 h vs. \> 6 h) and age (\< 50 years old vs. \> 50 years old).

CBT-I will be provided in six therapy sessions provided over an 8-week period by trained graduate therapists in clinical psychology. Lemborexant and placebo medication (compounded and coded by a pharmacy) will be provided by consulting physicians (blinded) in six consultations over an 8-week period. Physicians will have the option of increasing the initial starting dose from 5 mg to 10 mg if needed. Control participants will receive a placebo medication identical in size and color to the active medication.

The assessment phase will include baseline, post-treatment, and 6-month follow-up.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older at the time of enrolment
* Meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for insomnia disorder (Duke Sleep Interview), with total Insomnia Severity Index (ISI) score \> 10, and score ≥ 2 on either the interference or distress item
* Minimal symptoms of anxiety and/or depression with Patient Health Questionnaire (PHQ-9) \> 4 and/or Generalized Anxiety Disorder (GAD-7) \> 4
* Ability to read and understand French or English
* Ability to use a smartphone, tablet, or computer, and access to home internet connection

Exclusion Criteria:

* Presence of a lifetime diagnosis of any psychotic or bipolar disorder
* Untreated psychiatric disorder (e.g., major depression) or risk for suicide
* Substance/alcohol use disorder within the past year
* Any life-threatening or progressive medical illness (e.g., cancer, chronic obstructive pulmonary disease) or neurological degenerative disease (e.g., dementia)
* Current use of sleep-promoting medications (prescribed or over-the-counter) or cannabis-derived products for sleep more than two nights per week
* Current use of tricyclic antidepressants, monoamine oxidase inhibitors, or atypical antidepressants
* Reported diagnosis of sleep disorder other than insomnia (e.g., obstructive sleep apnea, restless legs syndrome, rapid eye movement behavior disorder, delayed phase sleep disorder, narcolepsy)
* Total score \> 5 on the Stop-Bang Questionnaire and/or clinical symptoms suggestive of sleep apnea (excessive daytime sleepiness), or Epworth score \> 10, restless legs syndrome or other signs of other sleep disorders
* Atypical sleep schedules (i.e., habitual bedtimes later than 2:00 AM and rising times later than 10:00 AM on more than two days/nights per week as documented from a sleep diary)
* Working night shifts more than five nights per month in the last six months
* Consuming 2 or more alcoholic beverages per day regularly (3 days or more per week)
* Any contra-indications to using the study medication, including lung disease/breathing problems (e.g., chronic obstructive pulmonary disease), use of strong or moderate CYP3A inducers (strong - rifampin, carbamazepine, and St. John's Wort) (moderate - bosentan, efavirenz, etravirine, and modafinil), pregnant and breastfeeding women
* Not using any method of birth control

Primary outcomes:
measure: Insomnia Symptom Severity
timeFrame: Baseline, during treatment period (weeks 0-8), at the end of the 2-week post-treatment and 6-month follow-up.
Secondary outcomes:
measure: Sleep onset latency from sleep diary
timeFrame: Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.
measure: Wake after sleep onset from sleep diary
timeFrame: Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.
measure: Total sleep time from sleep diary
timeFrame: Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.
measure: Sleep efficiency from sleep diary
timeFrame: Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.
measure: Depressive symptoms
timeFrame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
measure: Anxiety symptoms
timeFrame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
measure: Mental well-being
timeFrame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
measure: Fatigue
timeFrame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
measure: Functional impact of insomnia
timeFrame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
measure: Sleep-related beliefs and attitudes
timeFrame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
Other outcomes:
measure: Cognitive performance
timeFrame: Baseline and at the end of the 2-week post-treatment.
Locations:
city: Québec
country: Canada
facility: Université Laval Centre d'étude des troubles du sommeil
state: Quebec
Study officials:
affiliation: Université Laval Centre d'étude des troubles du sommeil
name: Charles M Morin, PhD
role: PRINCIPAL_INVESTIGATOR
References: