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

Overview

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.

Interventions

• 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.
• 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 pla
• 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 ti

Primary outcome measures

• Insomnia Symptom Severity [Time frame: Baseline, during treatment period (weeks 0-8), at the end of the 2-week post-treatment and 6-month follow-up.]

Secondary outcome measures (10)

• Sleep onset latency from sleep diary [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Nightly during 2-week pre-treatment, treatment period (weeks 0-8), 2-week post-treatment and 6-month follow-up.]
• Depressive symptoms [Time frame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.]
• Anxiety symptoms [Time frame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.]
• Mental well-being [Time frame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.]
• Fatigue [Time frame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.]
• Functional impact of insomnia [Time frame: Baseline, at the end of the 2-week post-treatment and 6-month follow-up.]
• Sleep-related beliefs and attitudes [Time frame: Baseline, at the end of the 2-week 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Université Laval Centre d'étude des troubles du sommeil — Québec

Publications

• Chen SJ, Ivers H, Dang-Vu TT, Shapiro CM, Carney CE, Robillard R, Morin CM. Efficacy of cognitive behavioral therapy for insomnia and lemborexant medication for different subtypes of chronic insomnia: study protocol for a randomized controlled trial. BMC Psychiatry. 2025 May 9;25(1):470. doi: 10.1186/s12888-025-06878-1. PMID 40346496

Identifiers

NCT: NCT06779149 · 2024-3057

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗