An Early Phase 1 interventional study of Inhaled Melatonin (100 μg) and Oral Melatonin (4 mg) in Insomnia, sponsored by Woolcock Institute of Medical Research. Recruiting at 1 site in Australia. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2025-07-18.
Sponsored by Woolcock Institute of Medical Research · Early Phase 1, Interventional, and Treatment
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:
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.
Exclusion Criteria:
100 µg daily of inhaled melatonin delivered by pressurized metered dose inhaler for two weeks before habitual bedtime.
Drug: Inhaled Melatonin (100 μg)
4 mg daily of orally delivered melatonin tablets for two weeks before habitual bedtime.
Drug: Oral Melatonin (4 mg)
An orally inhaled formulation of melatonin delivered by pressurised metered dose inhaler (pMDI) to be taken before bedtime. The pMDI will deliver a total of 100 μg of inhaled melatonin (2 x 50 μg/actuation). The investigational product is produced under Good Manufacturing Practice by Ab Initio Pharma Pty Ltd, a GMP certified manufacturer of pharmaceutical products.
Also known as: Melatonin
Two orally ingested tablets each containing 2 mg of melatonin (4 mg total) to be taken before bedtime. The investigational product is manufactured under Good Manufacturing Practice and is compliant with the TGA Therapeutic Order #101 that stipulates quality control requirements for capsule and pill-based products used in Australia.
Also known as: N-Acetyl-5-methoxytryptamine, Circadin, Melatonin
Sleep onset latency
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.
Time frame: Day 1
Insomnia Severity Index
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.
Time frame: Measured during the initial screening visit and day 14 of treatment.
Wake after sleep onset
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.
Time frame: Day 1
Total sleep time
Total sleep time (TST) is measured in minutes and is the sum of all 30 second epochs scored as sleep during an overnight polysomnogram.
Time frame: Day 1
Participant perception of sleep quality
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.
Time frame: Every observation for two weeks
Traditional sleep staging
Proportion of the sleep opportunity scored at the 5 stages (wake, and N1, N2, N3, and REM sleep) between lights out and lights on, measured using overnight in-laboratory polysomnography, scored by a polysomnography technician in accordance with AASM Sleep Scoring criteria.
Time frame: Day 1
Absolute Electroencephalography (EEG) Power During Non-Rapid Eye Movement (NREM) Sleep
Spectral power of low delta (0.5-1 Hz), delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges between treatment arms. Power spectral analysis will be applied to EEG signals from polysomnography during NREM sleep after artefacts are detected and removed.
Time frame: Day 1
Absolute Electroencephalography (EEG) Power During Rapid Eye Movement (REM) Sleep
Spectral power of low delta (0.5-1 Hz), delta (1-4.5 Hz), theta (4.5-8 Hz), alpha (8-12 Hz), sigma (12-15 Hz), beta (15-25 Hz), and gamma (25-40 Hz) frequency ranges between treatment arms. Power spectral analysis will be applied to EEG signals from polysomnography during REM sleep after artefacts are detected and removed.
Time frame: Day 1
Blood levels of glial fibrillary acidic protein
Blood-based glial fibrillary acidic protein (GFAP) within each participant, as measured by SIMOA blood neuro-metabolite assay.
Time frame: Day 14 of treatment.
Blood levels of interleukin-6
Blood-based interleukin-6 (IL-6), as measured by SIMOA blood neuro-metabolite assay.
Time frame: Day 14 of treatment.
Blood levels of plasma tau
Blood-based plasma tau within each participant, as measured by SIMOA blood neuro-metabolite assay.
Time frame: Day 14 of treatment.
Blood levels of granulocyte-macrophage colony-stimulating factor
Blood-based granulocyte-macrophage colony-stimulating factor (GM-CSF) within each participant, as measured by SIMOA blood neuro-metabolite assay.
Time frame: Day 14 of treatment.
Blood levels of brain derived neurotrophic factor
Blood-based brain derived neurotrophic factor (BDNF) within each participant, as measured by SIMOA blood neuro-metabolite assay.
Time frame: Day 14 of treatment.
Blood levels of neurofilament light chain
Blood-based neurofilament light chain (NFL) within each participant, as measured by SIMOA blood neuro-metabolite assay.
Time frame: Day 14 of treatment.
Blood levels of amyloid β (Aβ)
Blood-based Aβ (Aβ40:Aβ42 ratio) within each participant, as measured by SIMOA blood neuro-metabolite assay.
Time frame: Day 14 of treatment.
Blood levels of C-reactive protein
Blood-based C-reactive protein (CRP) within each participant, as measured by SIMOA blood neuro-metabolite assay.
Time frame: Day 14 of treatment.
Plan to share: Yes — Non-identifiable IPD will be shared upon reasonable request to the Principal Investigators.
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Woolcock Institute of Medical Research