Efficacy of CBT-I and Lemborexant Medication for Different Subtypes of Chronic Insomnia

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.

Study Overview

• Status: Recruiting
• Conditions: Insomnia Disorder
• Intervention / Treatment: Behavioral: Cognitive Behavioral Treatment for Insomnia (CBT-I); Drug: Lemborexant; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manon Lamy; Phone Number: 12467 418-656-2131; Email: manon.lamy@psy.ulaval.ca

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 0A6
      • Recruiting
      • Université Laval Centre d'étude des troubles du sommeil
      • Contact: Charles M Morin, PhD; Phone Number: 418-656-3275; Email: cmorin@psy.ulaval.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive Behavioral Treatment for Insomnia (CBT-I); Participants in this treatment group will receive CBT-I. CBT-I sessions will occur weekly for the first 4 sessions and biweekly for the last 2 sessions (treatment phase is thus 8 weeks). : Graduate level students in clinical psychology will serve as therapists for this project.	Behavioral: Cognitive Behavioral Treatment for Insomnia (CBT-I); Participants in this treatment group will receive CBT-I. CBT-I sessions will occur weekly for the first 4 sessions and biweekly for the last 2 sessions (treatment phase is thus 8 weeks). : Graduate level students in clinical psychology will serve as therapists for this project.
Experimental: Lemborexant medication; Participants assigned to this group will be prescribed 5 to 10 mg of lemborexant to be taken at bedtime in 5 mg capsules. Lemborexant (Dayvigo) is a Dual Orexin Receptor Antagonist approved by Health Canada for the treatment of adult with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. Pharmacy staff will package medications for each participant in a generic bottle labeled with the participant's ID code and treatment dates (identical for the lemborexant and placebo arms). Six consultation visits will be conducted during the 8-week treatment phase to monitor treatment response and drug side effects. The starting dose will be 5 mg with titration to 10 mg if needed (i.e., based on clinical response and tolerability) following the first week.	Drug: Lemborexant; Participants assigned to this group will be prescribed 5 to 10 mg of lemborexant to be taken at bedtime in 5 mg capsules. Lemborexant (Dayvigo) is a Dual Orexin Receptor Antagonist approved by Health Canada for the treatment of adult with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. Pharmacy staff will package medications for each participant in a generic bottle labeled with the participant's ID code and treatment dates (identical for the lemborexant and placebo arms). Six consultation visits will be conducted during the 8-week treatment phase to monitor treatment response and drug side effects. The starting dose will be 5 mg with titration to 10 mg if needed (i.e., based on clinical response and tolerability) following the first week.
Placebo Comparator: Placebo; Participants assigned to this group will be prescribed 5 to 10 mg of placebo to be taken at bedtime in 5 mg capsules identical to lemborexant. Pharmacy staff will package medications for each participant in a generic bottle labeled with the participant's ID code and treatment dates (identical for the lemborexant and placebo arms). Six consultation visits will be conducted during the 8-week treatment phase to monitor treatment response and drug side effects. The starting dose will be 5 mg with titration to 10 mg if needed (i.e., based on clinical response and tolerability) following the first week.	Drug: Placebo; Participants assigned to this group will be prescribed 5 to 10 mg of placebo to be taken at bedtime in 5 mg capsules identical to lemborexant. Pharmacy staff will package medications for each participant in a generic bottle labeled with the participant's ID code and treatment dates (identical for the lemborexant and placebo arms). Six consultation visits will be conducted during the 8-week treatment phase to monitor treatment response and drug side effects. The starting dose will be 5 mg with titration to 10 mg if needed (i.e., based on clinical response and tolerability) following the first week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insomnia Symptom Severity	Insomnia symptoms will be measured by the Insomnia Severity Index (ISI). The ISI is a self-report questionnaire evaluating seven dimensions of insomnia-severity of sleep onset, sleep maintenance, early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by sleep difficulties. Each item is rated on a 0 to 4 scale and the total score ranges from 0 to 28, with a higher total score suggesting more severe insomnia symptoms. An ISI score < 8 will be used to define remission. Treatment response will be defined at each assessment as a reduction of 8 points or more on the ISI compared with the baseline score.	Baseline, during treatment period (weeks 0-8), at the end of the 2-week post-treatment and 6-month follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep onset latency from sleep diary	Mean sleep onset latency per night in minutes from sleep diary.	Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.
Wake after sleep onset from sleep diary	Mean wake after sleep onset per night in minutes from sleep diary.	Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.
Total sleep time from sleep diary	Mean total sleep time per night in minutes from sleep diary.	Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.
Sleep efficiency from sleep diary	Mean sleep efficiency per night in percentage from sleep diary.	Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.
Depressive symptoms	The presence of symptoms of depression will be assessed by the Patient Health Questionnaire-9 (PHQ-9). Scores range from 0 to 27, with scores of 15 and higher suggesting the need for treatment.	Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
Anxiety symptoms	Anxiety symptom severity will be measured by the Generalised Anxiety Disorder 7-item (GAD-7). Scores range from 0 to 21, with scores of 15 and over suggesting severe anxiety.	Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
Mental well-being	Mental well-being will be measured by the 5-item World Health Organisation Well-Being Index (WHO-5). Scores range from 0 to 100, with higher scores indicating higher well-being.	Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
Sleep-related beliefs and attitudes	Sleep-related beliefs and attitudes will be measured by the Dysfunctional Beliefs and Attitudes about Sleep (DBAS-16). Higher scores indicate more dysfunctional beliefs and attitudes about sleep. The total score is calculated from the average score of all the items on the scale and could range from 0 to 10.	Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
Fatigue	Fatigue severity will be measured by the 9-item Fatigue Severity Scale (FSS). Scores range from 9 to 63 . higher score indicates more severe fatigue and impairment.	Baseline, at the end of the 2-week post-treatment and 6-month follow-up.
Functional impact of insomnia	Work and Social Adjustment Scale (WSAS) of 5 items will be used to measure how much sleep issues impair ability to function in terms of work, home management, leisure, and relationships. Scores range from 0 to 40. Higher scores indicate more work and social impairment.	Baseline, at the end of the 2-week post-treatment and 6-month follow-up.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive performance	Changes in cognitive performance measured by Cognitive Failures Questionnaire 2.0 (CFQ 2.0) will serve as an exploratory outcome. The CFQ 2.0 is a 15-item questionnaire asking respondents to rate the frequency with which they make minor mistakes (e.g., forgetting to take their keys, calling people by the wrong name). Scores range from 0 to 60, with higher scores indicating greater frequency of cognitive failures.	Baseline and at the end of the 2-week post-treatment.

Collaborators and Investigators

• Sponsor: Laval University
• Collaborators: The Royal Ottawa Mental Health Centre; Toronto Metropolitan University
• Investigators: Principal Investigator: Charles M Morin, PhD, Université Laval Centre d'étude des troubles du sommeil

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: January 12, 2025
• First Submitted That Met QC Criteria: January 12, 2025
• First Posted (Actual): January 16, 2025

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 5, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Insomnia; Lemborexant; Cognitive behavioral therapy for insomnia; Insomnia phenotypes; Objective short sleep duration
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Initiation and Maintenance Disorders; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Hypnotics and Sedatives; Lemborexant
• Other Study ID Numbers: 2024-3057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No