NCT06823752

A Dual Orexin Receptor Antagonist to Reduce Biomarkers of 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.

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Woolcock Institute of Medical Research · Academic / Other
• Sex: All
• Age: 40 Years – 65 Years
• Healthy volunteers: Not accepted

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).

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

Interventions

Type	Name	Description
DRUG	Lemborexant 10 MG	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.
DRUG	Placebo	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.

Timeline

• Start date: 2025-05-13
• Primary completion: 2026-04-01
• Completion: 2026-04-01
• First posted: 2025-02-12
• Last updated: 2025-10-03

Locations

1 site across 1 country: Australia

Regulatory

• FDA-regulated drug study