Clinical trial NCT04635098: DexmedetOmidine Complement Treats Chronic insOmnia and Improves Circadian Rhythm (DOCTOR)
Official title: The Effect of Dexmedetomidine on Patients With Chronic Insomnia and Its Influence on Circadian Rhythm:Randomized Clinical Trial, Double Blind
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Insomnia
Keywords: Chronic insomnia
Dexmedetomidine
Circadian Rhythm
Sleep monitoring
Brain functional connectivity
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2020-11-18
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sleep efficiency
timeFrame: Seven hours from day 0 23:30 to day 1 06:30
Secondary outcomes:
measure: BMAL1
timeFrame: Day 0,Day 1
measure: Brain functional connectivity
timeFrame: Seven hours from day 0 23:30 to day 1 06:30
measure: Interleukin-6(IL-6)
timeFrame: Day 0,Day 1
measure: Brain-derived neurotrophic factor(BDNF)
timeFrame: Day 0,Day 1
measure: N2 sleep time percentage
timeFrame: Seven hours from day 0 23:30 to day 1 06:30
measure: Deep brain functional connectivity
timeFrame: Day 0 before 22:00 , Day 3
measure: Cortisol
timeFrame: Day 0,Day 1
measure: Proteomic analysis
timeFrame: Day 0
measure: Sleep latency
timeFrame: Seven hours from day 0 23:30 to day 1 06:30
measure: Arousal
timeFrame: Seven hours from day 0 23:30 to day 1 06:30
measure: Sleep diary (sleep duration,sleep latency,arousal)
timeFrame: Day 1,Day 2,Day 3,Day 4,Day 5,Day 6,Day 7
measure: Pittsburgh Sleep Quality Index
timeFrame: Day0,Day7
measure: Insomnia severity index
timeFrame: Day0,Day7
measure: Epworth sleeping scale
timeFrame: Day0,Day7
measure: Hamilton anxiety scale
timeFrame: Day0,Day7
measure: Hamilton depression scale
timeFrame: Day0,Day7
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital
state: Shanghai
Study officials:
References:
citation: 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. doi: 10.1097/ALN.0000000000001325.
citation: 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.