Lemborexant for the Treatment of Residual Insomnia in Major Depressive Disorder (MDD)

ConditionsMajor Depressive Disorder(MDD)Insomnia Comorbid to Psychiatric Disorder

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-70

SponsorUnity Health Toronto

About this trial

The goal of this clinical trial is to learn if Lemborexant works to treat residual insomnia in adults with depression that is being treated. It will also learn about how practical, tolerable, and effective Lemborexant is. The main questions it aims to answer are:

* Does Lemborexant help participants improve sleep and reduce insomnia symptoms? * How practical is it to use Lemborexant (how many participants join, drop out, and follow the study rules)? How do participants feel about using it (based on surveys and interviews)?

Researchers will compare Lemborexant to a placebo (a look-alike substance that contains no drug) to see if Lemborexant works to treat residual insomnia in adequately treated major depressive disorder.

Participants will:

* Take Lemborexant or a placebo every day for 6 weeks (2 weeks at 5 mg then 4 weeks at 10 mg) * Complete clinical assessments and in-person study visits * Maintain a digital sleep diary and complete daily and weekly self-report ecological momentary assessments (EMAs) * Use a wearable device which will be used to collect and monitor physiological data

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Aged 18 to 70 (inclusive), with a self-reported body mass index (BMI) between 19 and 30 kg/m2 (inclusive);

Meet criteria for primary MDD diagnosis without psychotic symptoms, as defined by the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5)2, and currently in a MDE, confirmed by the MINI International Neuropsychiatric Interview (MINI)3;

Have not failed more than 2 trials of antidepressant treatments in the current MDE, and have a history of adequate response (clinical outcome rating score of 1 or 2) to at least 1 antidepressant treatment during the current MDE as determined by the Antidepressant Treatment History Form-Short Form (ATHF-SF)4;

Are outpatients;

Disqualifiers

Have taken or participated in any clinical trial of lemborexant and other drugs with the same mechanism (e.g., daridorexant), regardless of treatment outcome;

Have any known sensitivity to lemborexant or their excipients;

A lifetime history (current or previous) of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or psychotic symptoms as determined by the MINI;

Women who are pregnant or lactating (documented by a positive beta-human chorionic gonadotropin [beta-hCG] or human chorionic gonadotropin [hCG] urine test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG or hCG);

Trial design

Design model

Parallel

Treatments tested in this trial

Lemborexant
Drug
Dayvigo (lemborexant compound) is an orexin antagonist that acts on the arousal and sleep neural networks of the brain to regulate sleep-wake cycles and is used in the treatment of insomnia characterized by difficulties with sleep.
Placebo
Other intervention
The placebo is an inactive sugar pill that looks and tastes identical to the lemborexant pill.

Treatment groups

30 Participants

are divided into 2 treatment groups

Group A: LemborexantExperimental treatment 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

Feasibility Outcomes

Feasibility will be measured by the recruitment rate, withdrawal rate, data completion rate, and adherence rate. Recruitment rate will be quantified by the percentage of eligible participants enrolled relative to the number of participants contacted. Feasibility will be marked as a minimum of 1-2 participants enrolled per month. Withdrawal/dropout rate will be quantified by the percentage of participants who drop out of the study. The upper limit of the 95% confidence interval (CI) for dropout rate should not exceed 20%. Adherence and data completion will bhe proportion of participants who strictly follow the study protocol (the "per-protocol group") will be estimated with a 95% CI. This includes adherence to treatment (taking the medication correctly for six weeks), study completion (attending all required visits), and providing complete data. To be considered feasible, the lower limit of this 95% CI must be greater than 80%.

Time frame

13 weeks

Tolerability Outcomes

Tolerability will be measured by the frequency and nature of adverse events and medication adherence (i.e., missed dosage).

Time frame

10 weeks

Secondary outcomes

Preliminary Clinical Parameters

Changes in insomnia symptoms will be measured using the Insomnia Severity Index (ISI) Score. ISI score reduction will be compared between allocation and treatment end for participants randomized to receive Lemborexant and those receiving placebo.

Time frame

6 weeks

Within-person Correlations

Within-person changes in insomnia symptoms will be measured by within-person correlations of baseline and follow-up ISI scores. The ISI assesses the severity of insomnia symptoms, such as the impact of sleep on daytime functioning, difficulties with sleep onset, and sleep maintenance. Each item is rated on a scale from 0 (mild) to 4 (very severe), with a higher overall score indicating more severe insomnia presentations.

Time frame

10 weeks

Standard Deviation

Within and between participant variability in insomnia symptoms will be measured by standard deviation of ISI scores. This measure will be separate for each group (treatment and placebo).

Time frame

13 weeks

Change in Physiological Biometrics (Oura Ring Metrics)

Physiological biometrics will be captured using the Oura Ring and analyzed as a composite measure of changes across multiple parameters. Individual metrics will be reported separately and summarized as part of an overall physiological profile. The measured parameters include daily activity (step count (steps/day) and energy expenditure (METs)), heart rate metrics (resting heart rate (beats per minute) and heart rate variability (milliseconds)), body temperature (average nightly body temperature deviation (degrees Celsius), sleep quality (sleep latency, total time in bed, sleep staging (light, deep, REM sleep in minutes)), wake onset (minutes), and Oura composite scores (sleep, activity, and readiness scores (0-100 scale)). Statistical analyses will assess changes in each metric individually, as well as aggregated trends across sleep, activity, and recovery domains.

Time frame

13 weeks

Other outcomes

Patient Perspectives

Subjective patient experiences, thoughts, beliefs, and attitudes towards the digital health monitoring platforms (REDCap and Oura Ring) will be assessed using the user experience survey and semi-structured exit interviews. Open-ended feedback for considerations of future trials and digital intervention design will be considered.

Time frame

13 weeks