Insomnia
Conditions
Keywords
Electroencephalography, Sleep, Locus coeruleus, Hyperarousal
Brief summary
This research project aims to better understand the neurobiological mechanistic underpinnings of insomnia disorder. The main question is whether cortical hyperarousal in individuals with insomnia disorder, measured by electroencephalograhic (EEG) infraslow oscillation coupling of sigma power during non-rapid eye movement (NREM) sleep and theta power during rapid eye movement (REM) sleep, is related to locus coeruleus activity.
Detailed description
This trial is a double-blinded, placebo-controlled, randomised controlled cross over trial of dexmedetomidine or placebo in adults with insomnia disorder. Participants will be recruited using social media, bulletin boards and patient referrals from the Woolcock Institute of Medical Research clinics. Participants will be asked to complete an online pre-screening webpage (RedCap) to check for eligibility, and provided with the Participant Information Sheet (PIS) and asked for contact details for an in-person screening visit. The participants will have the study explained in detail during the screening visit followed by written informed consent. The participant will then undergo a medical screening for diagnosis of insomnia disorder and the medical officer will sign the consent form. Thereafter, the participant will complete baseline questionnaires and be randomised to either dexmedetomidine or placebo for the 2 sleep laboratory visits. Participants will then be instructed to maintain their regular sleep-wake patterns for seven days before the first sleep laboratory visit (Visit 1). During Visit 1, participants will undergo a number of assessments (pre-sleep locus coeruleus activity measured using pupillometry, electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS) before and during sleep and questionnaires about subjective hyperarousal. Participants will receive either dexmedetomidine or placebo. Following Visit 1, participants will have a 14-day washout, before Visit 2, which will repeat the procedures of Visit 1, but participants will receive the alternate condition (placebo or dexmedetomidine). The study will be coordinated from the Woolcock Institute of Medical Research, Sydney, Macquarie University, NSW, 2113, Australia.
Interventions
DRUGDexmedetomidine
A buccal tablet containing 96 µg dexmedetomidine will be taken before habitual bedtime.
DRUGPlacebo
Placebo tablets will contain identical excipient without the active ingredient (dexmedetomidine) 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.
Sponsors
Woolcock Institute of Medical Research
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All trial staff (except one unblinded researcher) and participants will be blinded to the intervention and control medication. We will use identical containers and labels except a patient identification code. The order of treatments will be secured in a password-protected data management system and known by the unblinded researcher.
Intervention model description
Double-blind, randomised, placebo-controlled crossover study
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of insomnia disorder (DSM-5-TR) * Insomnia severity index (ISI) score ≥15 * Able to provide informed consent * Fluent English literacy
Exclusion criteria
* Medically diagnosis of sleep disordered breathing (i.e. sleep apnea) or sleep or circadian disorder other than insomnia * Uncontrolled psychiatric disorders * High dependence on medical care * History of, or current suicide ideation (Patient Health Questionnaire (PHQ-9) questionnaire) * Pregnancy or actively trying to conceive, or lactating * Shiftwork - defined as work outside of business hours (before 8am or after 6pm) conducted at least once per week * Travel across time zones of over 2 h time difference in the past week * Contraindicate the patient's participation in the clinical trial due to safety concerns or compliance with clinical study procedures * Concomitant use of medicines that are inhibitors, or moderate to strong inducers, of CYP3A4; regular use of hypnotics and other medications that can cause additive sedation or psychostimulants or non-amphetamine psychostimulants within 14 days of starting the clinical trial * Ongoing use of THC- or CBD-containing products; dependence or any other drug or alcohol dependence * Allergy to lactose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Electrographic (EEG) signatures | Baseline and 14 days | Electrographic (EEG) infraslow oscillations (\~50 sec) of sigma power and sleep spindle coupling during non-rapid eye movement (NREM) sleep and theta power during rapid eye movement (REM) sleep. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Fragmentation | Baseline and 14 days | Polysomnography (PSG) measure conducted during the intervention and control (wake after sleep onset) |
| EEG power | Baseline and 14 days | Electroencephalographic (EEG) power during non-rapid eye movement (NREM) (stages 2 and 3) and rapid eye movement (REM) sleep. Unit of measurement is μV\^2. |
| Neurovascular activity (fNIRS) | Baseline and 14 days | Measurement of global blood flow using functional near-infrared spectroscopy (fNIRS). |
| Cardiopulmonary Coupling (CPC) | Baseline and 14 days | Cardiopulmonary coupling provides a global measure of autonomic function |
| Pupillometry | Baseline and 14 days | Pupil sizes will be assessed as a surrogate of locus coeruleus activity |
| Subjective hyperarousal | Baseline and 14 days | Pre-Sleep Arousal Scale (PSAS) before sleep. Scored by summing 16 items (rated 1 (not at all) to 5 (extremely)) with a total score between 16 to 80 |
| Subjective sleep quality | Baseline and 14 days | Self-reported rating of sleep quality (0-9) with higher scores indicating worse sleep. This will assessed in the morning after the overnight sleep study. |
Countries
Australia
Contacts
CONTACTChristopher Gordon, PhD
CONTACTCamilla Hoyos, PhD
PRINCIPAL_INVESTIGATORChristopher Gordon, PhD
Woolcock Institute of Medical Research
PRINCIPAL_INVESTIGATORBrendon Yee, MBChB, PhD
Woolcock Institute of Medical Research
Outcome results
None listed