Comparing inhaled and oral melatonin in adults with insomnia

A Novel Inhaled Formulation of Melatonin to Treat Adults With Insomnia Disorder: a Randomised Open-Label Crossover Trial

This will test whether a single inhaled dose of melatonin reaches peak levels and clears from the blood faster than a standard oral melatonin tablet in adults aged 55 and older with insomnia.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 55 Years and up
• Sex: All
• Sponsor: Woolcock Institute of Medical Research (Academic / other)
• Locations: 1 site (Macquarie Park, New South Wales)
• Trial ID: NCT06801379 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label crossover pharmacokinetic study comparing a 100 µg inhaled melatonin dose with a 4 mg oral melatonin tablet in adults with insomnia. Five participants will be randomized to receive each treatment on separate visits and provide serial blood samples over an approximately 8-hour daytime stay to measure absorption and elimination. Screening includes an online prescreen, review of a participant information sheet, and an in-person consent and eligibility check; included participants must meet DSM-5 insomnia criteria and have an ISI score ≥15. The primary measurements are time to peak blood concentration and clearance profiles for the two delivery methods.

Who should consider this trial

Good fit: Ideal candidates are adults aged 55 or older with DSM-5 insomnia, an ISI score of 15 or higher, and self-reported sleep onset latency of at least 30 minutes on three or more nights per week.

Not a fit: People with untreated moderate-to-severe sleep apnoea, circadian disorders, narcolepsy, severe restless legs syndrome, REM sleep behaviour disorder, uncontrolled psychiatric illness, high dependence on medical care, or those under 55 are unlikely to benefit from participation in this PK-focused study.

Why it matters

Potential benefit: If successful, inhaled melatonin could produce faster onset of blood melatonin at a much lower dose than oral tablets, which may translate to quicker sleep onset and fewer systemic effects.

How similar studies have performed: Oral melatonin is well studied for sleep, but inhaled melatonin formulations are novel and there is limited published human pharmacokinetic data on this delivery route.

Eligibility criteria

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).

Where this trial is running

Macquarie Park, New South Wales

• Woolcock Institute of Medical Research — Macquarie Park, New South Wales, Australia (Recruiting)

Study contacts

• Principal investigator: Hui Xin Ong, PhD — Woolcock Institute of Medical Research
• Study coordinator: Hui Xin Ong, PhD

Conditions Insomnia; Melatonin; Pharmacokinetics; Inhaled Therapy