DexmedetOmidine Complement Treats Chronic insOmnia and Improves Circadian Rhythm (DOCTOR)

Study Overview
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Brief Summary
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It has been reported that dexmedetomidine, alpha-2 adrenoceptor agonist, can activate endogenous neural sleep pathways in the central nervous system. This randomised, double-blinded and controlled trial was designed to investigate whether dexmedetomidine can improve/treat chronic insomnia patients. Its effects on sleep quality and improvement, EEG and circadian rhythm, brain connectivity, cognition and biomarker changes are determined.

Detailed Description
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Insomnia is a common sleep disorder characterized by difficulty in starting or maintaining sleep, or poor sleep quality and shortened sleep time. The prevalence of insomnia is about 10-20% of population worldwide; Of which about approximately 50% are chronic. Insomnia is a risk factor for cognitive impairment and mental disorder development, and other diseases. Non-pharmacological interventions, e.g. physio-therapy, are often ineffective. Benzodiazepines and their derivatives are commonly prescribed for those patients but their side effects and long-time residual sleepy actions are very risky. Dexmedetomidine is a highly selective α2 adrenergic receptor agonist with sedative, analgesic and anti-anxiety effects together with remarkable cytoprotective effects. It is widely used as a sedative. Dexmedetomidine was reported promote sleep. It can also modulate clock protein expression and hence afford a regulatory effects on the circadian rhythm. This randomised, double-blinded and controlled trial was designed to investigate whether dexmedetomidine can treat chronic insomnia patients. Its effects on sleep quality and improvement, EEG and circadian rhythm, brain connectivity, cognition and biomarker changes are determined. All participants are randomly assigned to receive either dexmedetomidine (a 0.5μg/kg bolus injection for 10 minutes followed by 0.1µg/kg/hr) or placebo (normal saline infusion with an identical protocol as Dex) for 8 hrs from 10pm to 6 am.

Official Title
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The Effect of Dexmedetomidine on Patients With Chronic Insomnia and Its Influence on Circadian Rhythm:Randomized Clinical Trial, Double Blind

Conditions
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Chronic Insomnia

Intervention / Treatment
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* Drug: dexmedetomidine
* Drug: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18- 65 years old Body mass index (BMI) between 18 and 35 kg/m^2； Clinical diagnosis of chronic insomnia； Must be able to communicate with site personnel Exclusion Criteria: Clinical diagnosis of mental disorders; Pregnancy; Current use of psychotropic drug ; Clinical diagnosis of neurological diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dexmedetomidine<br>0.5μg/kg bolus injection in 10 minutes followed by 0.1µg/kg/hr pump infusion from 22:00 pm to 6:00 am | Drug: dexmedetomidine<br>* All participants will be randomly assigned to receive either dexmedetomidine or saline<br>* Other names: dexmedetomidine group;|
| Placebo Comparator: saline<br>the same rate as dexmedetomidine | Drug: saline<br>* All participants will be randomly assigned to receive either dexmedetomidine or saline<br>* Other names: Placebo group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep efficiency | measured by Sleep monitor , Effective sleep time (the sum of non-rapid Eye movement sleep and rapid eye movement sleep time) as a percentage of the monitoring time. Monitoring time is eight hours | Eight hours from day 0 22:00 to day 1 06:00 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMAL1 | sleep protein , Collected from blood lymphocytes | Day 0，Day 1 | 
| Brain functional connectivity | According to the collected scalp EEG frequency domain and time domain data, the coherence method is used to measure the phase synchronization degree of different brain regions | Eight hours from day 0 22:00 to day 1 06:00 | 
| Cognition | measured by Scale scores（Mini-mental State Examination），Score from 0 to 30 points, the higher the score, the better the cognitive function | Day0, Day3, Day7 | 
| Interleukin-6(IL-6) | cytokines，Collected from blood | Day 0，Day 1 | 
| Brain-derived neurotrophic factor(BDNF) | Collected from blood | Day 0，Day 1 | 
| N2 sleep time percentage | measured by Sleep monitor，N2 sleep time as a percentage of total monitoring time. Monitoring time is eight hours | Eight hours from day 0 22:00 to day 1 06:00 | 
| Deep brain functional connectivity | we will analysis the brain connection network according to the functional magnetic resonance imaging nonlinear Granger predictive analysis (Granger causality analysis, GCA) method | Day 0 before 22:00 , Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic insomnia, Dexmedetomidine, Circadian Rhythm, Sleep monitoring, Brain functional connectivity