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

NCT06823752 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 16837
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Insomnia

Keywords

DORA; Tau; Beta Amyloid; Dementia; Sleep

Outcome Measures

Primary Outcomes (1)

• Blood levels of TAU181

  Morning blood-based phosphorylated TAU (standardised pTAU181:TAU181 ratio)

  5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.

Secondary Outcomes (4)

• Blood levels of TAU217

  5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.

• Blood levels of Beta amyloid

  5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.

• Blood levels of NFL

  5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.

• Blood levels of GFAP

  5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.

Other Outcomes (1)

• Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) (stages 2 and 3) and REM sleep.

  14th night after treatment starts.

Study Arms (2)

Dual Orexin Receptor Antagonist (DORA)

EXPERIMENTAL

10mg Lemborexant tablet taken orally, nightly for two weeks

Drug: Lemborexant 10 MG

Placebo

PLACEBO COMPARATOR

Matching placebo tablet taken orally, nightly for two weeks

Drug: Placebo

Interventions

Lemborexant 10 MG DRUG

An 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.

Also known as: Dayvigo

Dual Orexin Receptor Antagonist (DORA)

Placebo DRUG

Placebo 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.

Placebo

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Woolcock Institute of Medical Research: lead

Study Sites (1)

Woolcock Institute of Medical Research

Macquarie Park, New South Wales, 2113, Australia

RECRUITING

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Pick Disease of the Brain; Plaque, Amyloid; Dementia

Interventions

lemborexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Brain Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Camilla Hoyos, MPH, PhD

  Woolcock Institute of Medical Research

  PRINCIPAL INVESTIGATOR

• Brendon Yee, MBChB, FRACP, FCCP, PhD

  Woolcock Institute of Medical Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Camilla Hoyos, MPH, PhD

CONTACT

0438801044; camilla.hoyos@mq.edu.au

Rhearne Ryan, HScHons, PhD

CONTACT

+61 2 9805 3274; rhearne.ryan@woolcock.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study staff (except the unblinded investigator) and the participants will be blinded. Blinding will be maintained by the use of identical containers and labels except for the patient identification code. The order of treatment will be secured in a password-protected data management system and known by the unblinded trial epidemiologist and a second designated person independent of the study team as back-up in the event of emergency unblinding.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Leader

Model Details: Double-blind, randomised, placebo-controlled crossover study

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: February 12, 2025
• Study Start: May 13, 2025
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Non-identifiable IPD will become available one year after the Actual Study Completion Date and will be available for ten years.
• Access Criteria: A copy of the non-identifiable dataset may be requested by academic collaborators not affiliated with the WIMR through a data request form which outlines the investigators, aims and hypotheses, data to be included, a statistical analysis plan, ethics approval, and security measures. Contact the Coordinating Principal Investigator for access to data.

Locations

AU (1)