A Novel Inhaled Formulation of Melatonin to Treat Adults With Insomnia: Efficacy Study
ConditionInsomnia
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age55+
SponsorWoolcock Institute of Medical Research
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Crossover
Treatments tested in this trial
Inhaled Melatonin (100 μg)
DrugAn 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.
Oral Melatonin (4 mg)
DrugTwo 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.
Treatment groups
10 Participants
are divided into 2 treatment groupsGroup A: Inhaled Melatonin ArmExperimental treatment 1 intervention
Group B: Oral Melatonin ArmActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
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 1Secondary outcomes
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.2
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 13
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 14
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 weeksOther outcomes
1
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 12
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 13
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 14
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.Sponsors and contacts
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Source ClinicalTrials.gov