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

Chronic Insomnia Clinical Trial

— DOCTOR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04635098
• Other study ID #: DOCTOR-super LuoMa
• Status: Completed
• Phase: N/A
• Start date: May 14, 2021
• Est. completion date: March 7, 2024

Study information

• Verified date: March 2024
• Source: Ruijin Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: March 7, 2024
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Insomnia
• Sleep Initiation and Maintenance Disorders

Intervention

Drug:
• dexmedetomidine
All participants will be randomly assigned to receive either dexmedetomidine or saline
• saline
All participants will be randomly assigned to receive either dexmedetomidine or saline

Locations

Country	Name	City	State
China	Ruijin Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sleep efficiency	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	Seven hours from day 0 23:30 to day 1 06:30
Secondary	BMAL1	sleep protein , Collected from blood lymphocytes	Day 0,Day 1
Secondary	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	Seven hours from day 0 23:30 to day 1 06:30
Secondary	Interleukin-6(IL-6)	cytokines,Collected from blood	Day 0,Day 1
Secondary	Brain-derived neurotrophic factor(BDNF)	Collected from blood	Day 0,Day 1
Secondary	N2 sleep time percentage	measured by polysomnography,N2 sleep time as a percentage of total monitoring time. Monitoring time is eight hours	Seven hours from day 0 23:30 to day 1 06:30
Secondary	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
Secondary	Cortisol	Collected from blood	Day 0,Day 1
Secondary	Proteomic analysis	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	Day 0
Secondary	Sleep latency	measured by polysomnography,the time required from getting ready to go to bed to actually falling asleep	Seven hours from day 0 23:30 to day 1 06:30
Secondary	Arousal	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.	Seven hours from day 0 23:30 to day 1 06:30
Secondary	Sleep diary (sleep duration,sleep latency,arousal)	for one week after treatment recorded by the subjects themselves	Day 1,Day 2,Day 3,Day 4,Day 5,Day 6,Day 7
Secondary	Pittsburgh Sleep Quality Index	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.	Day0,Day7
Secondary	Insomnia severity index	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.	Day0,Day7
Secondary	Epworth sleeping scale	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.	Day0,Day7
Secondary	Hamilton anxiety scale	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.	Day0,Day7
Secondary	Hamilton depression scale	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.	Day0,Day7