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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Insomnia
• Intervention / Treatment: Drug: dexmedetomidine; Drug: saline

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 Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: saline; the same rate as dexmedetomidine	Drug: saline; All participants will be randomly assigned to receive either dexmedetomidine or saline; Other Names: Placebo group
Experimental: 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	Drug: dexmedetomidine; All participants will be randomly assigned to receive either dexmedetomidine or saline; Other Names: dexmedetomidine group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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	Seven hours from day 0 23:30 to day 1 06:30
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 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
Cortisol	Collected from blood	Day 0,Day 1
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): March 7, 2024

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Dexmedetomidine; Circadian Rhythm; Sleep monitoring; Chronic insomnia; Brain functional connectivity
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine
• Other Study ID Numbers: DOCTOR-super LuoMa

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Immediately following publication.No end date.
• IPD Sharing Access Criteria: Anyone who wishes to access the data for any research purpose.They can get all of the individual participant data collected during the trial, after deidentification.Proposals should be directed to d.ma@imperial.ac.uk/yqz12471@rjh.com.cn.To gain access, data requestors will need to sign a data access agreement. Proteomics data will be available at a website(iprox) following publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No