Using a dual orexin receptor antagonist to improve sleep and reduce neurodegeneration in adults with insomnia

A Dual Orexin Receptor Antagonist to Reduce Biomarkers of Neurodegeneration in Adults With Insomnia Disorder: a Randomised Placebo-controlled Cross-over Study.

This study is testing if a new sleep medication can help adults with insomnia sleep better and possibly protect their brain from damage.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 40 Years to 65 Years
• Sex: All
• Sponsor: Woolcock Institute of Medical Research (Academic / other)
• Locations: 1 site (Macquarie Park, New South Wales)
• Trial ID: NCT06823752 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of a dual orexin receptor antagonist (DORA), specifically Lemborexant, on biomarkers of neurodegeneration in adults suffering from insomnia. Participants will undergo a randomized, placebo-controlled, cross-over design where they will receive either the DORA or a placebo for two weeks, followed by a washout period before switching treatments. The study aims to measure changes in blood-based biomarkers associated with neurodegeneration, including phosphorylated TAU and amyloid beta levels, to assess the potential neuroprotective benefits of improved sleep. Participants will also undergo various assessments during overnight visits to gather comprehensive data on their sleep and neurological health.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 40-65 years with a diagnosis of insomnia disorder as defined by the DSM-5.

Not a fit: Patients with untreated moderate-severe sleep apnoea, severe psychiatric disorders, or other significant sleep disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option that not only improves sleep but also reduces the risk of neurodegeneration in adults with insomnia.

How similar studies have performed: While the approach of using a DORA for insomnia is relatively novel, similar studies targeting neurodegeneration through sleep improvement have shown promising results.

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.
* Able to provide informed electronic consent.
* Fluent English literacy.
* Adults aged between 40-65 years.

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. 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 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: Camilla Hoyos, MPH, PhD — Woolcock Institute of Medical Research
• Study coordinator: Camilla Hoyos, MPH, PhD

Conditions Insomnia; DORA; Tau; Beta Amyloid; Dementia; Sleep