Actively Recruiting

Phase 2
Age: 40Years - 65Years
All Genders
ID06823752

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

Led by Woolcock Institute of Medical Research · Updated on 2025-10-03

20

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are studying the potential neuroprotective effects of a dual orexin receptor antagonist (DORA) called Lemborexant in adults with insomnia. The main goal is to see if this treatment reduces blood biomarkers linked to neurodegeneration, including phosphorylated TAU181, TAU217, amyloid beta 40:42 ratio, Neurofilament Light Chain (NFL), and Glial Fibrillary Acidic Protein (GFAP) compared to a placebo. This is a randomized, placebo-controlled crossover study focusing on adults aged 40 to 65 with insomnia disorder. Participants will take 10mg of Lemborexant orally each night for two weeks and a matching placebo nightly for another two weeks, with a 2 to 4 week washout period between treatments. After each treatment phase, participants will visit the research facility for an overnight stay lasting about 18 hours. During this visit, they will undergo various assessments including high-density EEG, functional near-infrared spectroscopy, questionnaires, pupillometry, and blood sample collections. Throughout the study, participants will attend three visits: an initial screening and two overnight visits after each treatment period. Blood samples will be collected hourly for four hours following awakening during these visits to measure key biomarkers. Researchers will monitor sleep and brain activity, collect questionnaire data, and evaluate safety. The total involvement includes treatment periods, washout, and overnight assessments, ensuring thorough evaluation of treatment impact on neurodegeneration markers.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 40Years - 65Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Diagnosis of insomnia disorder as defined by the DSM-5 with symptoms at least 3 nights per week for at least 3 months
  • Insomnia Severity Index score of 15 or higher
  • Able to provide informed electronic consent
  • Fluent in English
  • Adults aged between 40 and 65 years
Not Eligible

You will not qualify if you...

  • Highly dependent on medical care as determined by a medical officer
  • Untreated moderate to severe sleep apnea (oxygen desaturation index >15) unless effectively treated
  • Circadian disorders, narcolepsy, severe restless legs syndrome, REM sleep behavior disorder, or uncontrolled psychiatric disorders
  • History of attempted suicide or current suicidal thoughts
  • Cognitive decline indicated by a Montreal Cognitive Assessment score of 26 or lower
  • Recent shift work, jet lag, or travel across more than 2 hours time difference within one week before randomization
  • Pregnancy or lactation; women advised to use contraception during study
  • Any condition posing safety concerns or affecting study compliance as judged by investigator
  • Participation in other investigational studies within 4 weeks prior to enrollment
  • Use of medications that strongly inhibit or induce CYP3A4 enzymes
  • Ongoing use of certain medications including antipsychotics, bosentan, efavirenz, etravirine, modafinil, rifampin, carbamazepine, illicit stimulants
  • Regular use of hypnotics, sedatives, or medications causing sedation within 14 days before trial start
  • Regular use of psychostimulants within 14 days before trial start
  • Recent changes in antidepressant treatment within past year
  • Regular opioid use within 14 days before trial start
  • Use of THC or CBD products within 14 days prior to trial
  • Drug or alcohol dependence within past two years (limited alcohol intake allowed during trial)
  • Allergy to lactose

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 screening and enrollment visit (in-person)

Treatment

Duration - 2 weeks

Participants take the study treatment orally, nightly for two weeks, either the dual orexin receptor antagonist (Lemborexant) or placebo.

2 treatment periods with a 2 to 4 week washout period between them

Overnight Assessment Visits

Duration - Approximately 18 hours per visit

At the end of each two-week treatment period, participants attend an overnight visit including sleep assessments, questionnaires, blood sample collection, and other measures.

2 overnight visits following each treatment period

Trial Site Locations

Total: 1 location

1

Woolcock Institute of Medical Research

Macquarie Park, New South Wales, Australia, 2113

Actively Recruiting

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Research Team

C

Camilla Hoyos, MPH, PhD

R

Rhearne Ryan, HScHons, PhD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

QUADRUPLE

Allocation

RANDOMIZED

Model

CROSSOVER

Primary Purpose

OTHER

Number of Arms

2

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