Understanding the Role of the Locus Coeruleus in Insomnia

Официальное название

An Alpha2-adrenoceptor Agonist to Reduce Locus Coeruleus Activity During Sleep in Adults With Insomnia Disorder: a Pilot Randomised Placebo-controlled Cross-over Study

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Dexmedetomidine
  A buccal tablet containing 96 µg dexmedetomidine will be taken before habitual bedtime.
• Препарат Placebo
  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.

Первичные конечные точки

• Electrographic (EEG) signatures [Срок оценки: Baseline and 14 days]

Вторичные конечные точки (7)

• Sleep Fragmentation [Срок оценки: Baseline and 14 days]
• EEG power [Срок оценки: Baseline and 14 days]
• Neurovascular activity (fNIRS) [Срок оценки: Baseline and 14 days]
• Cardiopulmonary Coupling (CPC) [Срок оценки: Baseline and 14 days]
• Pupillometry [Срок оценки: Baseline and 14 days]
• Subjective hyperarousal [Срок оценки: Baseline and 14 days]
• Subjective sleep quality [Срок оценки: Baseline and 14 days]

Критерии участия

Критерии включения

• Diagnosis of insomnia disorder (DSM-5-TR)
• Insomnia severity index (ISI) score ≥15
• Able to provide informed consent
• Fluent English literacy

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Другое

Центры проведения

Австралия · 1 центр

• Woolcock Institute of Medical Research — Macquarie Park

Идентификаторы

NCT: NCT07392177 · 19522

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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