A Dual Orexin Receptor Antagonist to Reduce Biomarkers of Neurodegeneration in Adults With Insomnia.

Recruiting now · Phase 2 · Has a placebo group

Conditions studied: Insomnia

In brief

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).

Key facts

Study ID

NCT06823752

Run by

Woolcock Institute of Medical Research

People needed

20

Starts

2025-05-13

Expected to finish

2026-04-01

Last updated by the study team

2025-10-03

Who can join

Age: 40 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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. Women will be advised to use contraception for the duration of the study and a urine pregnancy test will be performed when necessary.
• 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.
• Concomitant use of medicines that are inhibitors (e.g., diltiazem, fluvoxamine, fluconazole, itraconazole, verapamil), or moderate to strong inducers of CYP3A4 (e.g., carbamazepine, modafinil, phenytoin, rifampicin, St John's Wort)
• 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).
• Allergy to lactose.

Where it is running

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

Full record on ClinicalTrials.gov

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