The goal of this clinical trial is to explore the potential neuroprotective benefits of a dual orexin receptor antagonist (DORA) in adults with insomnia. The main questions it aims to answer are:
* Does the DORA reduce blood-based phosphorylated TAU181, in adults with insomnia, when compared to placebo * Does the DORA reduce other blood-based biomarkers of neurodegeneration, including phosphorylated TAU217, amyloid beta 40:42 ratio, Neurofilament Light Chain (NFL) and Glial Fibrillary Acidic Protein (GFAP), when compared to placebo.
Participants will:
* Take 10mg Lemborexant nightly for two weeks * Take a matching placebo nightly for two weeks * Visit the research institute for a screening visit and for an overnight visit at the conclusion of each study drug treatment (3 visits in total).
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.
Able to provide informed electronic consent.
Fluent English literacy.
Adults aged between 40-65 years.
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.
Crossover
Lemborexant 10 MG
DrugAn orally ingested tablet containing 10mg Lemborexant 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.
Placebo
DrugPlacebo tablets will contain similar excipients without the active ingredient (Lemborexant) and manufactured under the same condition as the active. Placebo tablets, packs and instructions will be identical in every respect to enable the double-blind study design.
Blood levels of TAU181
Morning blood-based phosphorylated TAU (standardised pTAU181:TAU181 ratio)
Blood levels of TAU217
Morning blood-based phosphorylated TAU217, analysed within each participant.
Blood levels of Beta amyloid
Morning blood-based Beta Amyloid 40:42 ratio, analysed within each participant.
Blood levels of NFL
Morning blood-based Neurofilament Light Chain (NFL), analysed within each participant.
Blood levels of GFAP
Morning blood-based Fibrillary Acidic Protein (GFAP), analysed within each participant.
Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) (stages 2 and 3) and REM sleep.
High-density EEG, spectral power for frequency ranges low-delta: 0.5-1 Hz; delta: 1-4.5 Hz; theta: 4.5-8Hz; alpha: 8-12Hz; sigma: 12-15 Hz; beta: 15-25 Hz; gamma: 25-40 Hz. Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) and REM sleep (12 statistical comparisons). Unit of measurement is μV\^2.
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