A Novel Inhaled Formulation of Melatonin to Treat Adults with Insomnia: Efficacy Study

Early Phase 1

Not yet recruiting

• Conditions: Insomnia
• Interventions: Drug: Inhaled Melatonin (100 μg); Drug: Oral Melatonin (4 mg)

• Registration Number: NCT06802913
• Lead Sponsor: Woolcock Institute of Medical Research

Brief Summary

The goal of this clinical trial is to explore the potential benefits of an inhaled version of melatonin compared to oral melatonin tablets on adults with insomnia. The main question the trial aims to answer is: does inhaled melatonin affect the sleep profiles of adults with insomnia differently than oral melatonin tablets?

10 Participants will:

* Visit the research institute for a screening visit, for an overnight visit at the beginning of each study drug treatment and for a blood collection visit at the end of the conclusion of each study drug treatment period (5 visits in total)

* Take 100 µg of inhaled melatonin (2 inhaler puffs) nightly for two weeks

* Take a 4 mg of oral melatonin (2 tablets) nightly for two weeks

Detailed Description

This is a randomised open-label cross-over study of an inhaled formulation of melatonin (100 µg) versus oral melatonin tablets (4 mg) in adults with insomnia. The experiments performed for this trial will examine the effects of inhaled and oral melatonin on sleep microarchitecture such as sleep onset latency.

To be enrolled in the trial, participants are required to complete an online pre-screening survey. Eligible participants will be directed to a separate webpage where they will be invited to review and download the Participant Information Sheet (PIS) and asked to provide their contact details and consent for a follow up call/email from the research team to book in a screening visit. At the screening visit, the study team will explain the study to each participant and provide the opportunity to ask any questions. The study team will also ensure participants have had ample time prior to the visit to read and understand the PIS. The consent form will be signed by both the participant and a medical officer and participants. Once participants have joined the efficacy study, they will be randomised into their first treatment group; inhaled melatonin (100 µg) or oral melatonin tablets (4 mg).

Participants will attend the laboratory for an overnight visit then be treated with either inhaled melatonin or oral melatonin tablets before completing an overnight polysomnography sleep study. After the sleep study, participants will continue to take the study drug every night for two weeks and complete a sleep diary each morning to assess participant subjective perception of sleep quality. Once the two weeks of treatment have been completed, participants will visit the laboratory again to provide a blood sample that will be examined for biomarkers of neuroinflammation. There will be a 1 week washout period between treatment periods.

The study will recruit primarily through social media advertisements. The study will be coordinated from the Woolcock Institute of Medical Research, Sydney, Macquarie University, NSW, 2113, Australia.

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2025-01-24
• Study First Submitted QC: 2025-01-24
• Last Update Submitted: 2025-03-24
• Study First Posted: 2025-03-25
• Last Update Posted: 2025-03-28
• Study Start: 2025-05
• Primary Completion: 2025-12
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Diagnosis of insomnia disorder as defined by the DSM-5 (difficulty initiating or maintaining sleep or waking up too early for at least 3 nights per week, for at least 3 months, with adequate opportunity and circumstances for sleep and at least one daytime impairment related to the sleep difficulty) and a score ≥15 on the ISI.
• History of subjective sleep onset latency (sSOL) ≥30 minutes on at least 3 nights per week in the previous 4 weeks.
• Able to provide informed electronic consent.
• Fluent English literacy.
• Adults aged 55+ years old.

Exclusion Criteria

• People highly dependent on medical care as determined by a medical officer.
• Untreated moderate-severe sleep apnoea as diagnosed using in-home wrist oximetry (oxygen desaturation index>15, ongoing effectively treated sleep apnoea with insomnia will be allowed).
• Circadian disorders, narcolepsy, severe restless legs syndrome, and REM sleep behaviour disorder or uncontrolled psychiatric disorders.
• History of attempted suicide or current suicide ideation (indicated by a score >0 on Q9 of the Patient Health Questionnaire-9) at pre-screening.
• Objective cognitive decline measured by scoring ≤26 on the Montreal Cognitive Assessment (MoCA)
• Regular shift work, jet lag or trans-meridian travel (over 2h time difference) in the past week before randomisation.
• Pregnancy or lactation. Female participants of childbearing potential with a fertile sexual partner must have a negative serum pregnancy test result at the screening visit. Women will be advised to use contraception for the duration of the study.
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical trial due to safety concerns or compliance with clinical study procedures.
• Currently participating in or has participated in a research study of an investigational agent or device within 4 weeks of enrolment.
• Ongoing use of anti-psychotic medication, bosentan, efavirenz, etravirine, modafinil, rifampin, carbamazepine or illicit stimulants.
• Regular use of hypnotics (including melatonin, valerian, kava, benzodiazepines and Z-drugs), and other medications that can cause additive sedation (e.g. sedating antihistamines, tricyclic antidepressants, antipsychotics) within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
• Regular use of psychostimulants (e.g., dexamfetamine, lisdexamfetamine, methylphenidate) or non-amphetamine psychostimulants (e.g., armodafinil, modafinil, atomoxetine) within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
• Use of antidepressant medications for treatment of low mood for less than one year or dose changes (escalation or tapering) or change in antidepressant medications within the past year.
• Regular use opioids within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
• Ongoing use of THC- or CBD-containing products within 14 days prior to the start of the trial.
• Dependence or any other drug or alcohol dependence within the past two years (alcohol to be limited to no more than 2 standard drinks per day during trial period).
• Regular use of drugs that are CYP1A2 inhibitors (e.g. amiodarone, cimetidine, ciprofloxacin, fluvoxamine) or CYP1A2 inducers (e.g. carbamazepine, phenobarbital, rifampin, tobacco).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Inhaled Melatonin Arm	Inhaled Melatonin (100 μg)	100 µg daily of inhaled melatonin delivered by pressurized metered dose inhaler for two weeks before habitual bedtime.
Oral Melatonin Arm	Oral Melatonin (4 mg)	4 mg daily of orally delivered melatonin tablets for two weeks before habitual bedtime.

Primary Outcome Measures

Name	Time	Method
Sleep onset latency	Day 1	Sleep onset latency (minutes) as assessed by polysomnography (PSG) on the first night of therapy. Sleep onset latency is the time between lights out and the first 30 second epoch scored as sleep using the American academy of sleep medicine criteria.

Secondary Outcome Measures

Name	Time	Method
Insomnia Severity Index	Measured during the initial screening visit and day 14 of treatment.	The Insomnia Severity Index (ISI) is a 7-item questionnaire used to examine overall insomnia severity. It consists of a five-point Likert type scale for each item (ranging from "no problem" = 0 to "severe problem" = 28) regarding symptoms over the past 2 weeks. Scores range from 0-28 with higher scores indicating greater insomnia symptom severity.
Wake after sleep onset	Day 1	Wake after sleep onset (WASO) is measured in minutes and is calculated from the first epoch of any sleep detected on the polysomnogram until the last epoch of sleep detected on the polysomnogram.
Total sleep time	Day 1	Total sleep time (TST) is measured in minutes and is the sum of all 30 second epochs scored as sleep during an overnight polysomnogram.
Participant perception of sleep quality	Every observation for two weeks	Ordinal rating of sleep quality (How would you rate the quality of your sleep? 9 = best ever sleep, 5 = neither best nor worst sleep, 1 = worst sleep ever), assessed in the Karolinska sleep diary after waking every day for two weeks.

Trial Locations

Locations (1)

Woolcock Institute of Medical Research; 🇦🇺 Macquarie Park, New South Wales, Australia