Major Depressive Disorder (MDD) With InsomniaPhase 3CombiChronoSNCT07120880
Efficacy of Chronotherapeutic Combination for Major Depressive Episode With Insomnia
A Phase 3 study testing AD + SHR + active LT and extended-release melatonin 2mg in people with Major Depressive Disorder (MDD) With Insomnia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Major Depressive Disorder (MDD) affects 5% of the global population and is the second leading cause of disability worldwide. Despite the widespread use of antidepressants, 50-60% of patients do not respond adequately after 8 weeks of treatment. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder (MDD) With Insomnia
- What is being tested?
- AD + SHR + active LT and extended-release melatonin 2mg
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 184 participants
- Where
- 1 siteFrance
- Study dates
- 28 Jan 2026to Jan 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged between 18 and 65 years (to avoid the risk of cataract associated with light therapy) with a diagnosis of a major depressive episode (MDE) in the context of unipolar depression (according to DSM-5 criteria).
- Diagnosis of comorbid insomnia with the MDE, defined by difficulty initiating sleep, and/or maintaining sleep, and/or early morning awakenings with daytime consequences, occurring at least three times per week (according to DSM-5 and ICSD-3, in line with European guideline recommendations).
- Outpatients or inpatients treated for MDE in one of the psychiatric departments of the study centers, or in the sleep medicine department, for a minimum treatment duration of 8 weeks.
- Patients not currently receiving antidepressant treatment for the current MDE (previous use of antidepressants is allowed, provided treatment was stopped at least one month prior to study participation).
- A MADRS score ≥ 20 (clinician-rated), indicating at least a moderate-intensity depressive episode.
- An ISI score ≥ 8 (clinician-rated), indicating at least mild and clinically significant insomnia.
Show all 9Show fewer
- No exposure to light therapy in the month prior to inclusion.
- Ability to understand and sign the informed consent form.
- Use of highly effective contraception for women of childbearing potential.
Who cannot join
- Individuals under legal guardianship or deprived of liberty
- Ophthalmologic conditions (e.g., cataract, glaucoma, age-related macular degeneration) or diseases affecting the retina (e.g., retinitis pigmentosa, diabetes, herpes, etc.)
- The following disorders (according to DSM-5): schizophrenia and other psychotic disorders; bipolar disorder, particularly (hypo)manic episodes (YMRS score ≥ 12); other unstable mental disorders
- Other unstable general medical conditions
- Pregnant or breastfeeding women
- Hypersomnia with prolonged total sleep time secondary to the depressive episode, according to ICSD-3 criteria
Show all 9Show fewer
- Current depressive episode already being treated with an antidepressant
- Presence of a high suicidal risk, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS, score ≥ 4)
- Ongoing melatonin treatment at the time of inclusion
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Bichat-Claude Bernard
Paris, 75018
Pierre-Alexis GEOFFROY, Pr, med, +33 1 40 25 62 72, pierrealexis.geoffroy@aphp.fr
Julia MARUANI, Dr, med, +33 1 40 25 62 72, julia.maruani@aphp.fr
About this study
Official title: Efficacy of a Combination of Chronotherapeutics for the Treatment of Major Depressive Episode (MDE) With Insomnia: a Multicenter, Randomized, 2*2 Factorial, Double-blind, Placebo-controlled Trial
Major Depressive Disorder (MDD) affects 5% of the global population and is the second leading cause of disability worldwide. Despite the widespread use of antidepressants, 50-60% of patients do not respond adequately after 8 weeks of treatment. Insomnia, present in approximately 85% of individuals with MDD, is a frequent and persistent symptom that contributes to poor treatment outcomes. Targeting insomnia has been shown to enhance both symptom remission and functional recovery. In this context, combined therapeutic strategies are often used to optimize the antidepressant response. Among them, chronotherapeutic approaches, such as light therapy and prolonged-release melatonin, have demonstrated rapid antidepressant effects and are beneficial in regulating sleep and circadian rhythms. Light therapy shows an efficacy comparable to antidepressants and, when used in combination with them, can double treatment effectiveness. Melatonin is also recommended in the management of depression-related insomnia. This multicenter, randomized, double-blind, placebo-controlled trial with a 2x2 factorial design aims to evaluate the efficacy of two chronotherapeutic interventions, 8 weeks of active light therapy and 2 mg of prolonged-release melatonin-administered alone or in combination, on depressive symptom reduction at 8 weeks in adult patients with MDD and comorbid insomnia. The primary outcome is the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 8. All participants will receive antidepressant treatment and sleep hygiene education. This study proposes a novel therapeutic strategy combining pharmacological and non-pharmacological interventions to address both depression and insomnia, with the goal of improving outcomes, especially for the 40% of patients who do not adequately respond to antidepressants alone.
Read the detailed description
Major Depressive Disorder (MDD) affects approximately 5% of the global population and represents the second leading cause of disability worldwide. Despite the availability of pharmacological treatments, particularly antidepressants, their efficacy remains limited: nearly 50 to 60% of patients do not respond adequately after 8 weeks of treatment. One of the most common and persistent symptoms in MDD is insomnia, which affects about 85% of patients and frequently persists even after partial improvement of mood symptoms. Insomnia is not only a residual symptom but also a marker of poor prognosis and treatment resistance. Addressing sleep disturbances directly has been shown to enhance both symptomatic and functional remission in depression, making it a promising target for intervention.
In clinical practice, combination strategies are increasingly employed to improve therapeutic response, particularly in patients who are only partially responsive to antidepressant medication. Among these strategies, chronotherapeutic interventions, such as light therapy and prolonged-release melatonin, offer a compelling approach. These treatments have demonstrated rapid antidepressant effects, with some studies reporting clinical improvements as early as the first week of treatment. Additionally, both interventions are known to positively influence sleep quality and circadian rhythm regulation, which are often disrupted in depressive disorders.
Light therapy (LT), in particular, has shown efficacy comparable to that of antidepressants and works by synchronizing the sleep-wake cycle. When used in combination with antidepressants, LT has been associated with significantly greater reductions in depressive symptoms than antidepressants alone. Similarly, prolonged-release melatonin has been recommended in the management of insomnia comorbid with depression, further supporting the rationale for combining these chronotherapeutic agents.
This study is a multicenter, randomized, double-blind, placebo-controlled trial designed in a 2x2 factorial format. It aims to evaluate the efficacy of two chronotherapeutic interventions, active light therapy (10,000 lux) for 8 weeks and 2 mg prolonged-release melatonin for 8 weeks, administered alone or in combination, in improving depressive symptoms at 8 weeks. The trial will enroll adult patients diagnosed with moderate to severe MDD and comorbid insomnia. The primary objective is to assess the change in depressive symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) score, from baseline to week 8.
All participants, regardless of group allocation, will receive standard antidepressant treatment and structured sleep hygiene counseling to ensure a consistent baseline of care. This approach reflects real-world practices and enhances the ecological validity of the trial. The study also incorporates objective and subjective measures of sleep and circadian rhythms to explore the broader impact of the interventions.
By evaluating the combined and individual effects of light therapy and melatonin alongside standard care, this study seeks to establish an innovative and comprehensive therapeutic model. The goal is to improve outcomes for individuals with MDD and insomnia, particularly the substantial proportion of patients, up to 40%, who do not achieve adequate response with antidepressants alone. This trial represents a significant step toward more personalized, effective, and integrated treatment strategies for depression.
- Being tested
- AD + SHR + active LT and extended-release melatonin 2mg, AD + SHR + active LT and placebo melatonin, AD + SHR + placebo LT and extended-release melatonin 2mg, AD + SHR + placebo LT and placebo melatonin
- Keywords
- Major depressive episode, Insomnia, Light therapy, Melatonin
- Medical subject headings
- Depressive Disorder, Major, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AD + SHR + active LT and extended-release melatonin 2mgProcedure or surgery
Patients will receive an SSRI antidepressant (e.g., Fluoxetine, Sertraline, Paroxetine, Escitalopram) or SNRI (e.g., Venlafaxine, Duloxetine) antidepressant (as clinically appropriate), combined with sleep hygiene education, daily morning LT (10,000 lux for 30 minutes between 7-8 a.m. using the Dayvia Slim Style 3 lamp), and 2 mg of extended-release melatonin taken one hour before bedtime, all for a duration of 8 weeks.
AD + SHR + active LT and placebo melatoninProcedure or surgery
Patients will receive an SSRI or SNRI, sleep hygiene instructions, daily morning bright LT (10,000 lux, 30 cm, 30 min, 7-8 a.m., using Dayvia Slim Style 3 lamps), and placebo melatonin taken one hour before bedtime, all for a duration of 8 weeks.
AD + SHR + placebo LT and extended-release melatonin 2mgProcedure or surgery
Patients will receive an SSRI or SNRI, sleep hygiene instructions, daily placebo light exposure (<10 lux, 30 cm, 30 min, 7-8 a.m., using Dayvia Slim Style 3 lamps in non-therapeutic mode), and 2 mg of extended-release melatonin taken one hour before bedtime, all for a duration of 8 weeks.
AD + SHR + placebo LT and placebo melatoninProcedure or surgery
Patients will receive an SSRI or SNRI, sleep hygiene instructions, daily placebo light exposure (<10 lux, 30 cm, 30 min, 7-8 a.m., using Dayvia Slim Style 3 lamps), and oral placebo melatonin taken one hour before bedtime, all for a duration of 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Patients receiving active light therapy (approx. 10,000 Lux) and prolonged-release melatonin 2 mg taken 1 hour before bedtime, in combination with sleep and hygiene rules (SHR) and antidepressant treatment (AD) Receives: Procedure: AD + SHR + active LT and extended-release melatonin 2mg |
| B | Active comparator | Patients receiving active light therapy (approx. 10,000 Lux) and placebo melatonin, in combination with SHR and AD. Receives: Procedure: AD + SHR + active LT and placebo melatonin |
| C | Active comparator | Patients receiving placebo light therapy (filtered to approx. <10 Lux) and prolonged-release melatonin 2 mg taken 1 hour before bedtime, in combination with SHR and AD. Receives: Procedure: AD + SHR + placebo LT and extended-release melatonin 2mg |
| D | Placebo comparator | Patients receiving placebo light therapy (filtered to approx. <10 Lux) and placebo melatonin (control group), in combination with SHR and AD. Receives: Procedure: AD + SHR + placebo LT and placebo melatonin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the efficacy of two chronotherapeutics (LT and extended-release melatonin 2mg), alone or combined, associated to AD on depressive symptoms reduction after 8 weeks of treatment
Measure the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score between the inclusion visit (V0, S0) and Week 8 (V3, S8) in patients with moderate to severe major depressive episode and insomnia
Measured: At baseline (Week 0) and at Week 8
Secondary outcomes (31)
Assessment of the efficacy of chronotherapeutics, combine or alone, on depressive symptoms evolution
Measure changes in MADRS scores from baseline (inclusion visit) to each follow-up visit (Week 1, Week 4, Week 8, and Month 3).
Measured: Weeks 1, 4, 8, and Month 3
Determination of the rate of therapeutic response to chronotherapeutics at each follow-up visit
Proportion of patients achieving ≥50% reduction in MADRS score at each follow-up visit (Week 1, Week 4, Week 8 and Month 3) as compared to baseline (inclusion visit)
Measured: Weeks 1, 4, 8, and Month 3
Determination of the rate of remission in depressive symptoms
Proportion of patients with MADRS score ≤10 at specified time points (Weeks 4, 8 and Month 3).
Measured: Weeks 4, 8, and Month 3
Evaluation of the impact of chronotherapeutics on subjective sleep
Assessment using self-reported sleep questionnaires, sleep-wake rhythm diaries, and sleep logs
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of the impact of chronotherapeutics on circadian rhythm
Assessment using self-reported sleep questionnaires, sleep-wake rhythm diaries, and sleep logs
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of changes in objective sleep measured by actigraphy
Total sleep time
Measured: Weeks 1, 4, and 8
Evaluation of changes in objective sleep measured by actigraphy
Wake After Sleep Onset (WASO)
Measured: Weeks 1, 4, and 8
Evaluation of changes in objective sleep measured by actigraphy
Fragmentation index
Measured: Weeks 1, 4, and 8
Evaluation of changes in objective sleep measured by actigraphy
Sleep efficiency
Measured: Weeks 1, 4, and 8
Evaluation of changes in objective sleep measured by actigraphy
Time in bed
Measured: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Total Sleep Time
Measured: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Wake After Sleep Onset (WASO)
Measured: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Fragmentation Index
Measured: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Sleep Efficiency
Measured: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Time in Bed
Measured: Weeks 1, 4, and 8
Evaluation of changes in objective actigraphy-derived sleep and rhythm parameters
Relative amplitude
Measured: Weeks 1, 4, and 8
Evaluation of changes in objective actigraphy-derived sleep and rhythm parameters
Interdaily stability/variability
Measured: Weeks 1, 4, and 8
Evaluation of changes in objective actigraphy-derived sleep and rhythm parameters
L5/M10 onset markers
Measured: Weeks 1, 4, and 8
Modeling of the longitudinal trajectory of MADRS scores
Analyze the slope of MADRS score changes across visits to characterize symptom progression or improvement.
Measured: From baseline to Week 8 and from baseline to Month 3
Measurement of time to therapeutic response
Time (in days) from inclusion to achievement of ≥50% reduction in MADRS score.
Measured: From baseline to Month 3
Evaluation of the tolerability of chronotherapeutic combinations
Evaluate adverse events using the PRISE-M side effects questionnaire.
Measured: Weeks 1, 4, and 8
Evaluation of mood state
Scores on YMRS (mania)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of mood state
C-SSRS (suicidal ideation)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of mood state
QIDS-SR (depression)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of mood state
GAD-7 (anxiety)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of mood state
CGI (clinical global impression)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
Scores on YMRS (mania)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
C-SSRS (suicidal ideation)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
QIDS-SR (depression)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
GAD-7 (anxiety)
Measured: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
CGI (clinical global impression)
Measured: Weeks 1, 4, 8, and Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2025
- Study start28 Jan 2026
- Primary completionAug 2028 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD) With InsomniaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 184 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre-Alexis GEOFFROY, Pr, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07120880
- Sponsor's protocol ID
- APHP230869
- Acronym
- CombiChronoS
- Status last verified
- Jul 2026
- First submitted
- 11 Jul 2025
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of a Combination of Chronotherapeutics for the Treatment of Major Depressive Episode (MDE) With Insomnia: a Multicenter, Randomized, 2*2 Factorial, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT07120880
- Acronym / sponsor ID
- CombiChronoS / APHP230869
- Keywords
- Major depressive episode, Insomnia, Light therapy, Melatonin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 184 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 28 Jan 2026 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 13 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Major Depressive Disorder (MDD) affects 5% of the global population and is the second leading cause of disability worldwide. Despite the widespread use of antidepressants, 50-60% of patients do not respond adequately after 8 weeks of treatment. Insomnia, present in approximately 85% of individuals with MDD, is a frequent and persistent symptom that contributes to poor treatment outcomes. Targeting insomnia has been shown to enhance both symptom remission and functional recovery. In this context, combined therapeutic strategies are often used to optimize the antidepressant response. Among them, chronotherapeutic approaches, such as light therapy and prolonged-release melatonin, have demonstrated rapid antidepressant effects and are beneficial in regulating sleep and circadian rhythms. Light therapy shows an efficacy comparable to antidepressants and, when used in combination with them, can double treatment effectiveness. Melatonin is also recommended in the management of depression-related insomnia. This multicenter, randomized, double-blind, placebo-controlled trial with a 2x2 factorial design aims to evaluate the efficacy of two chronotherapeutic interventions, 8 weeks of active light therapy and 2 mg of prolonged-release melatonin-administered alone or in combination, on depressive symptom reduction at 8 weeks in adult patients with MDD and comorbid insomnia. The primary outcome is the change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 8. All participants will receive antidepressant treatment and sleep hygiene education. This study proposes a novel therapeutic strategy combining pharmacological and non-pharmacological interventions to address both depression and insomnia, with the goal of improving outcomes, especially for the 40% of patients who do not adequately respond to antidepressants alone.
Detailed description
Major Depressive Disorder (MDD) affects approximately 5% of the global population and represents the second leading cause of disability worldwide. Despite the availability of pharmacological treatments, particularly antidepressants, their efficacy remains limited: nearly 50 to 60% of patients do not respond adequately after 8 weeks of treatment. One of the most common and persistent symptoms in MDD is insomnia, which affects about 85% of patients and frequently persists even after partial improvement of mood symptoms. Insomnia is not only a residual symptom but also a marker of poor prognosis and treatment resistance. Addressing sleep disturbances directly has been shown to enhance both symptomatic and functional remission in depression, making it a promising target for intervention.
In clinical practice, combination strategies are increasingly employed to improve therapeutic response, particularly in patients who are only partially responsive to antidepressant medication. Among these strategies, chronotherapeutic interventions, such as light therapy and prolonged-release melatonin, offer a compelling approach. These treatments have demonstrated rapid antidepressant effects, with some studies reporting clinical improvements as early as the first week of treatment. Additionally, both interventions are known to positively influence sleep quality and circadian rhythm regulation, which are often disrupted in depressive disorders.
Light therapy (LT), in particular, has shown efficacy comparable to that of antidepressants and works by synchronizing the sleep-wake cycle. When used in combination with antidepressants, LT has been associated with significantly greater reductions in depressive symptoms than antidepressants alone. Similarly, prolonged-release melatonin has been recommended in the management of insomnia comorbid with depression, further supporting the rationale for combining these chronotherapeutic agents.
This study is a multicenter, randomized, double-blind, placebo-controlled trial designed in a 2x2 factorial format. It aims to evaluate the efficacy of two chronotherapeutic interventions, active light therapy (10,000 lux) for 8 weeks and 2 mg prolonged-release melatonin for 8 weeks, administered alone or in combination, in improving depressive symptoms at 8 weeks. The trial will enroll adult patients diagnosed with moderate to severe MDD and comorbid insomnia. The primary objective is to assess the change in depressive symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) score, from baseline to week 8.
All participants, regardless of group allocation, will receive standard antidepressant treatment and structured sleep hygiene counseling to ensure a consistent baseline of care. This approach reflects real-world practices and enhances the ecological validity of the trial. The study also incorporates objective and subjective measures of sleep and circadian rhythms to explore the broader impact of the interventions.
By evaluating the combined and individual effects of light therapy and melatonin alongside standard care, this study seeks to establish an innovative and comprehensive therapeutic model. The goal is to improve outcomes for individuals with MDD and insomnia, particularly the substantial proportion of patients, up to 40%, who do not achieve adequate response with antidepressants alone. This trial represents a significant step toward more personalized, effective, and integrated treatment strategies for depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Procedure: AD + SHR + active LT and extended-release melatonin 2mgPatients receiving active light therapy (approx. 10,000 Lux) and prolonged-release melatonin 2 mg taken 1 hour before bedtime, in combination with sleep and hygiene rules (SHR) and antidepressant treatment (AD) |
| B | Active comparator | Procedure: AD + SHR + active LT and placebo melatoninPatients receiving active light therapy (approx. 10,000 Lux) and placebo melatonin, in combination with SHR and AD. |
| C | Active comparator | Procedure: AD + SHR + placebo LT and extended-release melatonin 2mgPatients receiving placebo light therapy (filtered to approx. <10 Lux) and prolonged-release melatonin 2 mg taken 1 hour before bedtime, in combination with SHR and AD. |
| D | Placebo comparator | Procedure: AD + SHR + placebo LT and placebo melatoninPatients receiving placebo light therapy (filtered to approx. <10 Lux) and placebo melatonin (control group), in combination with SHR and AD. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Adults aged between 18 and 65 years (to avoid the risk of cataract associated with light therapy) with a diagnosis of a major depressive episode (MDE) in the context of unipolar depression (according to DSM-5 criteria).
- Diagnosis of comorbid insomnia with the MDE, defined by difficulty initiating sleep, and/or maintaining sleep, and/or early morning awakenings with daytime consequences, occurring at least three times per week (according to DSM-5 and ICSD-3, in line with European guideline recommendations).
- Outpatients or inpatients treated for MDE in one of the psychiatric departments of the study centers, or in the sleep medicine department, for a minimum treatment duration of 8 weeks.
- Patients not currently receiving antidepressant treatment for the current MDE (previous use of antidepressants is allowed, provided treatment was stopped at least one month prior to study participation).
- A MADRS score ≥ 20 (clinician-rated), indicating at least a moderate-intensity depressive episode.
Key exclusion criteria (9 listed)
- Individuals under legal guardianship or deprived of liberty
- Ophthalmologic conditions (e.g., cataract, glaucoma, age-related macular degeneration) or diseases affecting the retina (e.g., retinitis pigmentosa, diabetes, herpes, etc.)
- The following disorders (according to DSM-5): schizophrenia and other psychotic disorders; bipolar disorder, particularly (hypo)manic episodes (YMRS score ≥ 12); other unstable mental disorders
- Other unstable general medical conditions
- Pregnant or breastfeeding women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AD + SHR + active LT and extended-release melatonin 2mgPatients will receive an SSRI antidepressant (e.g., Fluoxetine, Sertraline, Paroxetine, Escitalopram) or SNRI (e.g., Venlafaxine, Duloxetine) antidepressant (as clinically appropriate), combined with sleep hygiene education, daily morning LT (10,000 lux for 30 minutes between 7-8 a.m. using the Dayvia Slim Style 3 lamp), and 2 mg of extended-release melatonin taken one hour before bedtime, all for a duration of 8 weeks. | Procedure or surgery | A |
| AD + SHR + active LT and placebo melatoninPatients will receive an SSRI or SNRI, sleep hygiene instructions, daily morning bright LT (10,000 lux, 30 cm, 30 min, 7-8 a.m., using Dayvia Slim Style 3 lamps), and placebo melatonin taken one hour before bedtime, all for a duration of 8 weeks. | Procedure or surgery | B |
| AD + SHR + placebo LT and extended-release melatonin 2mgPatients will receive an SSRI or SNRI, sleep hygiene instructions, daily placebo light exposure (<10 lux, 30 cm, 30 min, 7-8 a.m., using Dayvia Slim Style 3 lamps in non-therapeutic mode), and 2 mg of extended-release melatonin taken one hour before bedtime, all for a duration of 8 weeks. | Procedure or surgery | C |
| AD + SHR + placebo LT and placebo melatoninPatients will receive an SSRI or SNRI, sleep hygiene instructions, daily placebo light exposure (<10 lux, 30 cm, 30 min, 7-8 a.m., using Dayvia Slim Style 3 lamps), and oral placebo melatonin taken one hour before bedtime, all for a duration of 8 weeks. | Procedure or surgery | D |
Primary outcome
Assessment of the efficacy of two chronotherapeutics (LT and extended-release melatonin 2mg), alone or combined, associated to AD on depressive symptoms reduction after 8 weeks of treatment
Time frame: At baseline (Week 0) and at Week 8
Measure the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score between the inclusion visit (V0, S0) and Week 8 (V3, S8) in patients with moderate to severe major depressive episode and insomnia
31 secondary outcomes
Assessment of the efficacy of chronotherapeutics, combine or alone, on depressive symptoms evolution
Time frame: Weeks 1, 4, 8, and Month 3
Determination of the rate of therapeutic response to chronotherapeutics at each follow-up visit
Time frame: Weeks 1, 4, 8, and Month 3
Determination of the rate of remission in depressive symptoms
Time frame: Weeks 4, 8, and Month 3
Evaluation of the impact of chronotherapeutics on subjective sleep
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of the impact of chronotherapeutics on circadian rhythm
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of changes in objective sleep measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in objective sleep measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in objective sleep measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in objective sleep measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in objective sleep measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in sleep rhythm parameters measured by actigraphy
Time frame: Weeks 1, 4, and 8
Evaluation of changes in objective actigraphy-derived sleep and rhythm parameters
Time frame: Weeks 1, 4, and 8
Evaluation of changes in objective actigraphy-derived sleep and rhythm parameters
Time frame: Weeks 1, 4, and 8
Evaluation of changes in objective actigraphy-derived sleep and rhythm parameters
Time frame: Weeks 1, 4, and 8
Modeling of the longitudinal trajectory of MADRS scores
Time frame: From baseline to Week 8 and from baseline to Month 3
Measurement of time to therapeutic response
Time frame: From baseline to Month 3
Evaluation of the tolerability of chronotherapeutic combinations
Time frame: Weeks 1, 4, and 8
Evaluation of mood state
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of mood state
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of mood state
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of mood state
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of mood state
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
Time frame: Weeks 1, 4, 8, and Month 3
Evaluation of global functioning evolution
Time frame: Weeks 1, 4, 8, and Month 3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Individual participant dataSharing planned: No
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Insomnia, Depression - Major Depressive Disorder
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Efficacy and Safety of Daridorexant in Patients With Major Depressive Disorder and Insomnia
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Psychiatric Disorder, Depression
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Efficacy and Safety of Low-dose Laser Acupuncture on Treating Insomnia Associated With Major Depressive Disorder
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pierre-Alexis GEOFFROY, Pr principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AD + SHR + active LT and extended-release melatonin 2mg in people with Major Depressive Disorder (MDD) With Insomnia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pierre-Alexis GEOFFROY, Pr, med (+33 1 40 25 62 72, pierrealexis.geoffroy@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the efficacy of two chronotherapeutics (LT and extended-release melatonin 2mg), alone or combined, associated to AD on depressive symptoms reduction after 8 weeks of treatment (time frame: At baseline (Week 0) and at Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.