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The goal of this clinical trial is to evaluate whether the timing and dosage of exogenous melatonin can improve sleep onset and maintenance in healthy adults aged 18-45 years (50% female) with no history of sleep disorders.
The main questions it aims to answer is whether an optimized melatonin administration schedule (4 mg, 3 hours before bedtime) will be more effective in improving sleep initiation and maintenance than an administration schedule more commonly advised (2 mg, 30 minutes before bedtime).
Researchers will compare five conditions involving different combinations of melatonin or placebo administered 30 minutes or 3 hours before bedtime to see if earlier timing and/or higher dosage produces better sleep outcomes.
Participants will:
Complete a habituation night without any intervention.
Undergo five randomized, double-blind experimental sleep conditions including:
2 mg melatonin 30 minutes before bedtime 2 mg melatonin 3 hours before bedtime 4 mg melatonin 30 minutes before bedtime 4 mg melatonin 3 hours before bedtime Placebo at both time points
Be monitored via polysomnography to measure sleep parameters
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2mg 30min | Active Comparator |
| |
| 2mg 3h | Experimental |
| |
| 4mg 30min | Experimental |
| |
| 4mg 3h | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mel 2 mg 30 min | Dietary Supplement | Melatonin 2 mg 30 minutes before bedtime, placebo 3 hours before bedtime |
|
| Measure | Description | Time Frame |
|---|---|---|
| Sleep Onset Latency | Time required to fall asleep assessed using polisomnography | First night following administration of the drug |
| Measure | Description | Time Frame |
|---|---|---|
| Total Sleep Time | Night sleep duration assessed using polisomnography | First night following administration of the drug |
| Sleep Efficiency | Ratio between total sleep time and time in bed |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ugo Faraguna, MD, PhD | Contact | +39 050 2213470 | ugo.faraguna@unipi.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pisa, Institute of Physiology, Sonnolab | Pisa | PI | 56126 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40914024 | Background | Bruno S, Cenerini G, Lo Giudice L, Cruz-Sanabria F, Benedetti D, Crippa A, Fiori S, Ferri R, Masi G, Faraguna U. Optimizing timing and dose of exogenous melatonin administration in neuropsychiatric pediatric populations: a meta-analysis on sleep outcomes. Sleep Med Rev. 2025 Dec;84:102158. doi: 10.1016/j.smrv.2025.102158. Epub 2025 Aug 30. | |
| 38888087 |
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The data cannot be shared publicly for the privacy of individuals who participated in the study
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 27, 2023 | Jan 10, 2026 | SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 27, 2023 | Jan 10, 2026 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D012893 | Sleep Wake Disorders |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D006722 | Honey |
| ID | Term |
|---|---|
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
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| Mel 2 mg 3 h | Dietary Supplement | Placebo administered 30 minutes before bedtime, melatonin 2 mg administered 3 hours before bedtime |
|
| Mel 4 mg 30 min | Dietary Supplement | Melatonin 4 mg administered 30 minutes before bedtime, placebo administered 3 hours before bedtime |
|
| Mel 4 mg 3 h | Dietary Supplement | Placebo administered 30 minutes before bedtime, melatonin 4 mg administered 3 hours before bedtime |
|
| Placebo | Other | Placebo administered 30 minutes before bedtime, placebo administered 3 hours before bedtime |
|
| First night following administration of the drug |
| Wake After Sleep Onset | Minutes spent awake between the sleep onset and morning awakening | First night following administration of the drug |
| Cruz-Sanabria F, Bruno S, Crippa A, Frumento P, Scarselli M, Skene DJ, Faraguna U. Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis. J Pineal Res. 2024 Aug;76(5):e12985. doi: 10.1111/jpi.12985. |
| D001523 | Mental Disorders |