CBT-I + Lemborexant for Insomnia

Overseen By Manon Lamy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Laval University

Must not be taking: Sleep-promoting, Tricyclics, MAOIs, Atypicals

Disqualifiers: Psychotic, Bipolar, Substance use, others

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two treatments—cognitive behavioral therapy for insomnia (CBT-I) and the medication lemborexant—on sleep and mental health in individuals with insomnia and some anxiety or depression. Researchers seek to determine if those who sleep less than six hours respond differently to these treatments compared to those who sleep more. The trial suits individuals who struggle with sleep and experience symptoms of anxiety or depression. Participants should not be using sleep medications or have other sleep disorders, such as sleep apnea. As an unphased trial, this study offers participants the chance to contribute to valuable research that could enhance treatment options for insomnia and mental health.

Will I have to stop taking my current medications?

The trial requires that you stop taking sleep-promoting medications or cannabis-derived products for sleep more than two nights per week, as well as tricyclic antidepressants, monoamine oxidase inhibitors, or atypical antidepressants. If you are using any of these, you would need to stop before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Cognitive Behavioral Treatment for Insomnia (CBT-I) is safe and effective. It works as well as sleep medication but without side effects. Users of CBT-I often continue to see improvements in their sleep over time.

Regarding lemborexant, studies have found it to be generally well-tolerated. The most common side effect is drowsiness, occurring in about 7.65% of users. Some also experience nightmares or unusual dreams, though these are less common. Long-term studies have found lemborexant to be safe for use over several months.

Both treatments have demonstrated safety in past research, but participants should monitor how they feel and report any concerns to the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for insomnia because they combine Cognitive Behavioral Treatment for Insomnia (CBT-I) with Lemborexant, a Dual Orexin Receptor Antagonist. Most insomnia treatments, like benzodiazepines or melatonin receptor agonists, focus on general sedation or sleep-wake cycle regulation. However, Lemborexant specifically targets orexin receptors, which play a key role in wakefulness, potentially reducing side effects like next-day grogginess. Additionally, CBT-I is a non-drug approach that addresses the behavioral and psychological aspects of insomnia, offering a holistic treatment option. This combination could enhance treatment effectiveness by tackling both the physical and mental components of insomnia.

What evidence suggests that this trial's treatments could be effective for insomnia?

Research has shown that Cognitive Behavioral Therapy for Insomnia (CBT-I), which participants in this trial may receive, improves sleep quality. One study found that people fell asleep 19 minutes faster on average and experienced better overall sleep. CBT-I significantly reduces insomnia symptoms.

Similarly, lemborexant, another treatment option in this trial, has proven effective. Studies found it helped people stay asleep longer by improving sleep efficiency and reducing the time awake during the night. Lemborexant received high ratings compared to other insomnia treatments. Both CBT-I and lemborexant offer promising options for improving sleep in people with insomnia. ^{1 3 6 7 8}

Who Is on the Research Team?

Charles M Morin, PhD

Principal Investigator

Université Laval Centre d'étude des troubles du sommeil

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic insomnia and mild anxiety or depression. Participants must meet DSM-5 criteria for insomnia, have an Insomnia Severity Index score above 10, and be able to use digital devices with internet access. They should also understand French or English.

Inclusion Criteria

I can read and understand either French or English.

I can use a smart device or computer and have home internet.

I have mild symptoms of anxiety or depression.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive either CBT-I, lemborexant, or placebo over an 8-week period with six consultations

8 weeks

6 visits (in-person)

Post-treatment

Participants are assessed for treatment response and side effects

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cognitive Behavioral Treatment for Insomnia (CBT-I)
• Lemborexant

Trial Overview The study compares the effectiveness of Cognitive Behavioral Treatment for Insomnia (CBT-I) and Lemborexant medication against a placebo in improving sleep and mental health in people with different subtypes of chronic insomnia.

How Is the Trial Designed?

Group I: Lemborexant medication Experimental Treatment 1 Intervention

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.

Group II: Cognitive Behavioral Treatment for Insomnia (CBT-I) Experimental Treatment 1 Intervention

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.

Group III: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Laval University

Lead Sponsor

Trials

439

Recruited

178,000+

Toronto Metropolitan University

Collaborator

Trials

95

Recruited

19,300+

The Royal Ottawa Mental Health Centre

Collaborator

Trials

24

Recruited

2,300+

Published Research Related to This Trial

Cognitive Behavioral Therapy for insomnia (CBT-i) is an effective first-line treatment for chronic insomnia, showing significant improvements in sleep onset latency (SOL) by about 19 minutes and wake after sleep onset (WASO) by about 26 minutes based on a review of 20 studies involving 1162 participants.

The benefits of CBT-i, which includes techniques like cognitive therapy and sleep hygiene, appear to be sustained over time, and importantly, no adverse effects were reported, making it a safe alternative to pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy for Chronic Insomnia: A Systematic Review and Meta-analysis. Trauer, JM., Qian, MY., Doyle, JS., et al.[2022]

Cognitive Behavioral Therapy for Insomnia (CBT-I) significantly improved sleep quality, sleep onset, and sleep efficiency in 76 patients with primary insomnia over a 6-week group course in a clinical setting.

CBT-I also led to reductions in medication use and improvements in patients' overall health and cognitive functioning, highlighting its effectiveness beyond just sleep improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cognitive-behavioural therapy for primary insomnia: effectiveness in a clinical setting]. Van Houdenhove, L., Buyse, B., Gabriels, L., et al.[2018]

Lemborexant, a dual orexin receptor antagonist, demonstrated significant and sustained improvements in sleep onset and maintenance over twelve months in a study involving 949 participants, with benefits maintained from the initial six months of treatment.

The treatment was generally safe, with most adverse events being mild to moderate, and there was no evidence of rebound insomnia or withdrawal symptoms after discontinuation, indicating its potential for long-term use in managing insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial. Yardley, J., Kärppä, M., Inoue, Y., et al.[2021]

Cognitive-behavioral therapy for insomnia (CBT-I) showed positive effects on sleep quality and depressive symptoms in a study of 30 psychiatric outpatients, with 38% achieving normal sleep after treatment.

While CBT-I led to significant improvements within the treatment group over 4 and 8 weeks, there were no significant differences when compared to the control group, suggesting that while beneficial, the effects may not be strong enough to outperform standard care alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of abbreviated CBT for insomnia in psychiatric outpatients: sleep and depression outcomes. Wagley, JN., Rybarczyk, B., Nay, WT., et al.[2022]

Cognitive Behavioral Therapy for Insomnia (CBT-I) significantly improves sleep quality in adults with insomnia and comorbid medical or psychiatric conditions, based on a review of 23 studies involving 1379 patients.

The treatment leads to substantial reductions in sleep onset latency and wake after sleep onset, with benefits lasting up to 18 months, demonstrating its effectiveness and durability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavioral therapy in persons with comorbid insomnia: A meta-analysis. Geiger-Brown, JM., Rogers, VE., Liu, W., et al.[2022]

Cognitive behavioral therapy for insomnia (CBT-I) is a safe and effective treatment for insomnia, even in patients with various co-occurring mental health and medical conditions.

The article reviews the evidence supporting the use of CBT-I in these populations and discusses important considerations for its application, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy for Insomnia in Patients with Medical and Psychiatric Comorbidities. Raglan, GB., Swanson, LM., Arnedt, JT.[2019]

Lemborexant has been shown to significantly reduce the time it takes to fall asleep compared to placebo and is also effective when compared to the active control zolpidem ER, based on two phase 3 trials.

The medication is generally well-tolerated, with fewer severe side effects like cognitive impairment and complex sleep-related behaviors compared to traditional insomnia treatments, making it a suitable option, especially for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder. Waters, K.[2022]

Cognitive behavioral therapy for insomnia (CBT-I) is recognized as the first-line treatment for both uncomplicated insomnia and insomnia associated with other chronic disorders, demonstrating its broad efficacy.

This review aims to summarize efficacy data across various clinical and demographic factors and to outline future research and implementation strategies for CBT-I, highlighting its importance in treating sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

We know CBT-I works, now what? Muench, A., Vargas, I., Grandner, MA., et al.[2022]

Cognitive-behavioral therapy for insomnia (CBT-I) is the preferred treatment for chronic insomnia, but it faces challenges such as a lack of trained therapists and a low response rate among patients.

Alternative methods to CBT-I, including bibliotherapy, phone psychotherapy, brief behavioral therapy, and online CBT-I, are gaining interest, and hypnotics can be used alongside CBT-I to enhance its effectiveness or as a standalone treatment when CBT-I is not accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cognitive-behavioral therapy and pharmacotherapy for chronic insomnia]. Pchelina, PV., Poluektov, MG.[2019]

In a study of 649 patients with comorbid insomnia and psychiatric disorders, lemborexant was found to be effective, with a response rate of 64.5% and over 60% for most psychiatric conditions.

Lemborexant significantly reduced the dosage of benzodiazepines (BZs) used by patients, indicating its potential to help manage insomnia while decreasing reliance on these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia. Katsuta, N., Takahashi, K., Kurosawa, Y., et al.[2023]

Cognitive behavior therapy for insomnia (CBT-I) shows moderate to large treatment effects (Cohen's d range of 0.35-2.2) for patients with insomnia related to various medical and psychiatric conditions, indicating its efficacy beyond primary insomnia.

Improving sleep through CBT-I may also lead to better outcomes in managing comorbid medical and psychological conditions, highlighting the need for further research on adapting CBT-I for specific disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavior therapy for chronic insomnia occurring within the context of medical and psychiatric disorders. Smith, MT., Huang, MI., Manber, R.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6796223/

Cognitive-Behavioral Therapy for Insomnia: An Effective ... A 2015 meta-analysis of 20 randomized controlled studies of CBT-i for patients with chronic insomnia found average reductions of 19 minutes in sleep latency and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S138994572500156X

Effectiveness of group-delivered cognitive behavioural ... Results from a meta-analysis showed that group-delivered CBT-I led to improved sleep quality and better sleep, especially regarding sleep onset latency, sleep ...

3. jcsm.aasm.org jcsm.aasm.org/doi/10.5664/jcsm.11756

main outcomes of a randomized dismantling trial All groups exhibited insomnia symptom reduction at posttreatment (CT: d = −2.53, P < .001; BT: d = −2.39, P < .001; CBT: d = −2.90, P < .001) ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2803668

Digital Cognitive Behavioral Therapy vs Medication ... In this study, clinical evidence suggested that combination therapy was optimal, and dCBT-I was more effective than medication therapy, with long-term benefits ...

5. nature.com nature.com/articles/s41746-025-01847-0

A randomized controlled trial of a digital cognitive ... Results indicate that digital CBT-I provides important benefits for older adults, offering strong potential to expand access to insomnia ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1389945725002862

Predictors and moderators of cognitive therapy ... Predicting clinically significant response to cognitive behavior therapy for chronic insomnia in general medical practice: analyses of outcome data at 12 months ...

7. kosinmedj.org kosinmedj.org/journal/view.php?number=1311

a focus on components of cognitive behavioral therapy for ... A 2023 network meta-analysis confirmed the individual effectiveness of SCT in insomnia treatment, despite variations in guideline details, ...

8. frontiersin.org frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1413694/full

The efficacy of cognitive behavioral therapy for insomnia in ... CBT-I was effective in improving insomnia in adolescents and some sleep-related outcomes, including sleep onset latency, total sleep time, and sleep efficiency.