DexmedetOmidine Complement Treats Chronic insOmnia and Improves Circadian Rhythm (DOCTOR)
- Registration Number
- NCT04635098
- Lead Sponsor
- Ruijin Hospital
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- 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
- Clinical diagnosis of mental disorders;
- Pregnancy;
- Current use of psychotropic drug ;
- Clinical diagnosis of neurological diseases
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description dexmedetomidine dexmedetomidine 0.5μg/kg bolus injection in 10 minutes followed by 0.1µg/kg/hr pump infusion from 23:30 pm to 6:30 am saline saline the same rate as dexmedetomidine
- Primary Outcome Measures
Name Time Method Sleep efficiency Seven hours from day 0 23:30 to day 1 06:30 measured by polysomnography, 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
- Secondary Outcome Measures
Name Time Method Epworth sleeping scale Day0,Day7 A scale for evaluating daytime sleepiness, with higher scores indicating greater daytime sleepiness in subjects.The minimum value is 0 points, and the maximum value is 24 points.
Cortisol Day 0,Day 1 Collected from blood
BMAL1 Day 0,Day 1 sleep protein , Collected from blood lymphocytes
Pittsburgh Sleep Quality Index Day0,Day7 Scale to assess sleep quality，the lower the score, the better the sleep quality.The minimum value is 0 points, and the maximum value is 21 points.
Deep brain functional connectivity Day 0 before 22:00 , Day 3 we will analysis the brain connection network according to the functional magnetic resonance imaging nonlinear Granger predictive analysis (Granger causality analysis, GCA) method
Proteomic analysis Day 0 Due to some patients having a good response to Dex treatment, while others had rather limited efficacy, we further investigated the proteomic differences in peripheral blood between effective and ineffective patients before their treatment.Screening differential proteins between two groups in the protein database through proteomic analysis results in peripheral blood samples
Insomnia severity index Day0,Day7 Scale to assess severity of insomnia,the higher the score, the more severe the insomnia will be.The minimum value is 0 points, and the maximum value is 28 points.
Hamilton anxiety scale Day0,Day7 A scale for assessing anxiety levels, where the higher the score, the more anxious the subject is.daytime sleepiness in subjects.The minimum value is 0 points, and the maximum value is 56 points.
Hamilton depression scale Day0,Day7 A scale for assessing the degree of depression, with higher scores indicating greater depression among participants.
0-7 points: No depressive symptoms or normal level; 8-13 points: Mild depressive symptoms; 14-18 points: moderate depressive symptoms; 19-22 points: symptoms of moderate to severe depression; 23 points or above: severe depressive symptoms.N2 sleep time percentage Seven hours from day 0 23:30 to day 1 06:30 measured by polysomnography，N2 sleep time as a percentage of total monitoring time. Monitoring time is eight hours
Sleep latency Seven hours from day 0 23:30 to day 1 06:30 measured by polysomnography，the time required from getting ready to go to bed to actually falling asleep
Brain functional connectivity Seven hours from day 0 23:30 to day 1 06:30 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
Arousal Seven hours from day 0 23:30 to day 1 06:30 measured by polysomnography including arousal \> 15 sec(times), micro arousal(times) and wake duration after sleep onset(min).These indicators are used to evaluate the number of awakenings during sleep and the total duration of awakenings.
Sleep diary (sleep duration,sleep latency,arousal) Day 1,Day 2,Day 3,Day 4,Day 5,Day 6,Day 7 for one week after treatment recorded by the subjects themselves
Interleukin-6(IL-6) Day 0,Day 1 cytokines，Collected from blood
Brain-derived neurotrophic factor(BDNF) Day 0,Day 1 Collected from blood
Trial Locations
- Locations (1)
Ruijin Hospital
🇨🇳Shanghai, Shanghai, China