InsomniaPhase 2Neuro-DORANCT06823752
A Dual Orexin Receptor Antagonist to Reduce Biomarkers of Neurodegeneration in Adults With Insomnia.
A Phase 2 study testing Lemborexant 10 MG in people with Insomnia, run by Woolcock Institute of Medical Research at 1 site in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 65 years
- Conditions the study is for
- Insomnia
- What is being tested?
- Lemborexant 10 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteAustralia
- Study dates
- 13 May 2025to Dec 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site, 1 recruiting
- Recruiting
Woolcock Institute of Medical Research
Macquarie Park, New South Wales, 2113
Grigori Kaplan, PhD, +61 9114 0412, grigori.kaplan@sydney.edu.au
Camilla Hoyos, PhD
About this study
Official title: A Dual Orexin Receptor Antagonist to Reduce Biomarkers of Neurodegeneration in Adults With Insomnia Disorder: a Randomised Placebo-controlled Cross-over Study.
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.
Read more
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).
Read the detailed description
This is a randomised placebo-controlled cross-over study of a dual orexin receptor antagonist (DORA) versus placebo in adults with insomnia.
To be enrolled in the study, participants are required to complete an online pre-screening survey. Eligible participants will be directed to a separate webpage where they will be invited to review and download the Participant Information Sheet (PIS) and asked to provide their contact details and consent for a follow up call/email from the research team to book in a screening visit. At the screening visit the study team will explain the study to each participant and ensure they have had ample time prior to the visit to read and understand the PIS and have had the opportunity to ask any questions. The consent form will be signed by both the participant and a medical officer and participants will be randomised into their first treatment period; DORA (Lemborexant) or placebo.
Participants will take the treatment orally, nightly for 2 weeks. There will be a 2-4 week washout period between treatments. At the conclusion of both two-week treatment phases, participants will attend the laboratory for an overnight visit. The visit will take approximately 18 hours (including sleep time). During this visit, participants will partake in a number of assessments including HD-EEG, fNIRS, questionnaires and pupillometry. Participants will also have blood samples collected in the morning of the overnight study (hourly for four hours).
The study will recruit primarily through social media advertisements. The study will be coordinated from the Woolcock Institute of Medical Research, Sydney, Macquarie University, NSW, 2113, Australia.
- Conditions
- Insomnia
- Being tested
- Lemborexant 10 MG, Placebo
- Keywords
- DORA, Tau, Beta Amyloid, Dementia, Sleep
- Medical subject headings
- Sleep Initiation and Maintenance Disorders, Pick Disease of the Brain, Plaque, Amyloid, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lemborexant 10 MGDrug
Also called Dayvigo
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dual Orexin Receptor Antagonist (DORA) | Experimental | 10mg Lemborexant tablet taken orally, nightly for two weeks Receives: Drug: Lemborexant 10 MG |
| Placebo | Placebo comparator | Matching placebo tablet taken orally, nightly for two weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood levels of TAU181
Morning blood-based phosphorylated TAU (standardised pTAU181:TAU181 ratio)
Measured: 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
Morning blood-based phosphorylated TAU217, analysed within each participant.
Measured: 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
Morning blood-based Beta Amyloid 40:42 ratio, analysed within each participant.
Measured: 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
Morning blood-based Neurofilament Light Chain (NFL), analysed within each participant.
Measured: 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
Morning blood-based Fibrillary Acidic Protein (GFAP), analysed within each participant.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2025
- Study start13 May 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InsomniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, randomised, placebo-controlled crossover study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Woolcock Institute of Medical Research
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Camilla Hoyos, Woolcock Institute of Medical Research
- Investigators
- Camilla Hoyos, MPH, PhD, Principal investigator, Woolcock Institute of Medical ResearchBrendon Yee, MBChB, FRACP, FCCP, PhD, Principal investigator, Woolcock Institute of Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06823752
- Sponsor's protocol ID
- 16837
- Acronym
- Neuro-DORA
- Status last verified
- Sep 2026
- First submitted
- 28 Jan 2025
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Non-identifiable IPD will be shared upon reasonable request to the Principal Investigators.