DexmedetOmidine Complement Treats Chronic insOmnia and Improves Circadian Rhythm (DOCTOR)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: dexmedetomidine 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
All participants will be randomly assigned to receive either dexmedetomidine or saline
Other Names:
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| Placebo Comparator: saline the same rate as dexmedetomidine |
Drug: saline
All participants will be randomly assigned to receive either dexmedetomidine or saline
Other Names:
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Outcome Measures
Primary Outcome Measures
- Sleep efficiency [Eight hours from day 0 22:00 to day 1 06:00]
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
Secondary Outcome Measures
- BMAL1 [Day 0，Day 1]
sleep protein , Collected from blood lymphocytes
- Brain functional connectivity [Eight hours from day 0 22:00 to day 1 06:00]
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
- Cognition [Day0, Day3, Day7]
measured by Scale scores（Mini-mental State Examination），Score from 0 to 30 points, the higher the score, the better the cognitive function
- Interleukin-6(IL-6) [Day 0，Day 1]
cytokines，Collected from blood
- Brain-derived neurotrophic factor(BDNF) [Day 0，Day 1]
Collected from blood
- N2 sleep time percentage [Eight hours from day 0 22:00 to day 1 06:00]
measured by Sleep monitor，N2 sleep time as a percentage of total monitoring time. Monitoring time is eight hours
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age between 18- 65 years old
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Body mass index (BMI) between 18 and 35 kg/m^2；
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Clinical diagnosis of chronic insomnia；
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Must be able to communicate with site personnel
Exclusion Criteria:
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Clinical diagnosis of mental disorders;
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Pregnancy;
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Current use of psychotropic drug ;
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Clinical diagnosis of neurological diseases
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ruijin Hospital | Shanghai | Shanghai | China | 200025 |
Sponsors and Collaborators
- Ruijin Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Akeju O, Hobbs LE, Gao L, Burns SM, Pavone KJ, Plummer GS, Walsh EC, Houle TT, Kim SE, Bianchi MT, Ellenbogen JM, Brown EN. Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study. Clin Neurophysiol. 2018 Jan;129(1):69-78. doi: 10.1016/j.clinph.2017.10.005. Epub 2017 Oct 20.
- Wu XH, Cui F, Zhang C, Meng ZT, Wang DX, Ma J, Wang GF, Zhu SN, Ma D. Low-dose Dexmedetomidine Improves Sleep Quality Pattern in Elderly Patients after Noncardiac Surgery in the Intensive Care Unit: A Pilot Randomized Controlled Trial. Anesthesiology. 2016 Nov;125(5):979-991.
- DOCTOR-super LuoMa