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Intranasal Dexmedetomidine and Zolpidem for Treatment of Primary Insomnia

Primary Purpose

Insomnia

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Dexmedetomidine
Zolpidem
Placebo
Sponsored by
The University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Insomnia focused on measuring Insomnia, Dexmedetomidine, Zolpidem

Eligibility Criteria

18 Years - 25 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Participants aged between 18 to 25 years, with DSM-5 insomnia disorder. Insomnia will be diagnosed and confirmed by a clinical interview and will have an Insomnia Severity Index score of ≥ 15. Exclusion Criteria: Comorbid diagnosis of psychiatric disorders ( major depression, anxiety disorders, bipolar disorders and psychotic disorders) Obstructive sleep apnoea as determined by an Apnea Hypoapnea Index of >15 or snoring. Restless legs, or periodic limb movements during sleep as measured by the Periodic Limb Movements Index with arousal of > 15 per hour Obesity (body mass index > 30) Known or suspected cardiovascular, pulmonary, metabolic disease or diabetes as confirmed by the clinician interview during recruitment Pregnancy Anyone who has taken trans-meridian travel across more than one time-zone or worked night shifts in the preceding three months Consuming prescribed or non-prescription sleep medication in the past month

Sites / Locations

  • HKU Li Ka Shing Faculty of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Dexmedetomidine

Zolpidem

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Sleep onset latency
Sleep onset latency is a measure of how long it takes for the participant to fall asleep once the participant gets into bed. This will be measured in minutes and reported as minutes for each of the treatments

Secondary Outcome Measures

Incidence of wakening after sleep onset; Sleep quality; Wake time during sleep
Incidence of wakening after sleep onset: This is a measure of how many times the participant will wake up after falling asleep. It will be measured as count data. Sleep quality: This is a subjective measure and will be given as a score from a survey completed by the participant. The data will be reported as count data Wake time during sleep: This will be detected with the polysomnography and will be reported in total minutes

Full Information

First Posted
October 12, 2022
Last Updated
November 7, 2022
Sponsor
The University of Hong Kong
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1. Study Identification

Unique Protocol Identification Number
NCT05615727
Brief Title
Intranasal Dexmedetomidine and Zolpidem for Treatment of Primary Insomnia
Official Title
A Randomized, Placebo-controlled Crossover Trial of Intranasal Dexmedetomidine and Zolpidem for Treatment of Primary Insomnia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2022 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Insomnia is a significant public health burden, increasing work absenteeism and health care costs in a large proportion of the population. It causes altered cognition, emotional disturbances, and reduced quality of life. The purpose of this study is to determine whether the sleep promoting effect of dexmedetomidine is superior to the conventional sleep promoting drug, zolpidem. The main outcome of this study is to measure the time taken to fall asleep. Investigators will also look at incidences of wakening after sleep onset, sleep quality and wake time during sleep.
Detailed Description
Insomnia is a significant public health burden, increasing work absenteeism and health care costs in a large proportion of the population. It causes altered cognition, emotional disturbances, and reduced quality of life. Most epidemiologic studies have found that about one-third of adults report at least one symptom of insomnia e.g. difficulty initiating sleep or maintaining sleep. There are also similar problems related to circadian rhythm disturbance as seen in shift workers and "jet lag". Research indicates that DNA damage is apparent in doctors subjected to sleep deprivation. Traditional currently available hypnotics which are used to initiate and maintain sleep ("sleeping tablets") are either benzodiazepines (BZD) or the so-called Z-drugs (zolpidem, zopiclone and zaleplon) which are a class of psychoactive drugs that are very benzodiazepine-like in nature and act by allosterically activating gamma-aminobutyric acid receptor A (GABAA). They have virtually superseded benzodiazepines but have almost entirely the same pharmacodynamic effects and, therefore, exhibit similar action, side-effects, and risks. Despite their name, these drugs do not induce natural sleep as manifest by EEG. They are central nervous system depressants that disproportionately promote non-rapid eye movement (NREM) sleep while suppressing REM sleep. Selective REM sleep deprivation in humans has adverse effects on memory consolidation and pain perception. Other problems with these drugs include numerous reports of misuse, abuse and dependence, paradoxical reactions, increased risk of road traffic accidents and exacerbation of asthma. A retrospective cohort study of more than 100,000 age- and sex-matched patients showed that those who used these drugs were 3 times more likely to die prematurely during the 7 -year follow-up period than those who did not, with significant dose-response associations shown for benzodiazepines and the "Z drugs". New evidence-based clinical practice guidelines for the treatment of insomnia disorder were recently developed using the GRADE methodology (Grading of Recommendations, Assessment, Development, and Evaluation) and represent the first comprehensive, systematic analysis of single agents for treatment. Unfortunately, the level of evidence for all recommendations was "weak" meaning that the strength of the evidence in the published data were low. Notably, all the recommended treatments for sleep onset insomnia, besides ramelteon, a melatonin receptor agonist , are Z-drugs or BZD hypnotics. For sleep maintenance insomnia, three of five of the treatment options are Z-drugs or BZDs. The US Food and Drug Administration has recently put a Boxed Warning on Z drugs since serious injuries and death from complex sleep behaviours have occurred in patients with and without a history of such behaviours. These behaviours can occur after just one dose. Clearly, better pharmacological treatment is warranted. Dexmedetomidine is a highly selective alpha-2 adrenergic receptor antagonist that acts on the locus ceruleus1 in the brain to produce dose dependent sedation, anxiolysis and analgesia with no respiratory depression and only modest haemodynamic effects. It has been extensively studied and used for both adult and paediatric sedation, premedication, intensive care and in perioperative settings to prevent emergence delirium after anaesthesia. The sedative effect of this drug is unique in that it produces prominent slow wave activity in the electroencephalogram (EEG) resembling stage 2 NREM sleep with facilitated arousal (as with natural sleep). Of the sleeping states, the NREM sleep period seems fundamental because it happens first (wakefulness to NREM) and lasts the longest. It has even been suggested as a suitable drug to induce torpor in manned space flight. The intravenous formulation is also efficacious when administered by the intranasal route in both children and adults. Since this is not associated with any unpleasant sensation, there is increasing use for paediatric premedication and procedural sedation. The bioavailability of intranasal dexmedetomidine administered by atomiser or by drops is approximately 40% in healthy adult volunteers with an inter-individual variability of around 30%. The pharmacokinetic and pharmacodynamic profiles of the two modes of administration are similar and both are equally effective in inducing adequate sedation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insomnia
Keywords
Insomnia, Dexmedetomidine, Zolpidem

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Model Description
Each participant will take part in three sleep investigations. Each sleep investigation will take place after the participant has completed one night of sleep familiarization in the laboratory. The 3 sleep investigations will be conducted after administration of the following in a randomised manner: Placebo Intranasal dexmedetomidine Zolpidem
Masking
ParticipantOutcomes Assessor
Masking Description
placebo-controlled crossover trial
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dexmedetomidine
Arm Type
Experimental
Arm Title
Zolpidem
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Intervention Description
2 mcg/kg of undiluted dexmedetomidine [= 0.02 ml/kg] and oral placebo tablet
Intervention Type
Drug
Intervention Name(s)
Zolpidem
Intervention Description
zolpidem 10 mg and intranasal saline 0.02 ml/kg
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
a placebo oral tablet and intranasal saline at 0.02 ml/kg
Primary Outcome Measure Information:
Title
Sleep onset latency
Description
Sleep onset latency is a measure of how long it takes for the participant to fall asleep once the participant gets into bed. This will be measured in minutes and reported as minutes for each of the treatments
Time Frame
720 minutes
Secondary Outcome Measure Information:
Title
Incidence of wakening after sleep onset; Sleep quality; Wake time during sleep
Description
Incidence of wakening after sleep onset: This is a measure of how many times the participant will wake up after falling asleep. It will be measured as count data. Sleep quality: This is a subjective measure and will be given as a score from a survey completed by the participant. The data will be reported as count data Wake time during sleep: This will be detected with the polysomnography and will be reported in total minutes
Time Frame
720 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participants aged between 18 to 25 years, with DSM-5 insomnia disorder. Insomnia will be diagnosed and confirmed by a clinical interview and will have an Insomnia Severity Index score of ≥ 15. Exclusion Criteria: Comorbid diagnosis of psychiatric disorders ( major depression, anxiety disorders, bipolar disorders and psychotic disorders) Obstructive sleep apnoea as determined by an Apnea Hypoapnea Index of >15 or snoring. Restless legs, or periodic limb movements during sleep as measured by the Periodic Limb Movements Index with arousal of > 15 per hour Obesity (body mass index > 30) Known or suspected cardiovascular, pulmonary, metabolic disease or diabetes as confirmed by the clinician interview during recruitment Pregnancy Anyone who has taken trans-meridian travel across more than one time-zone or worked night shifts in the preceding three months Consuming prescribed or non-prescription sleep medication in the past month
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Micheal Garnet Irwin, M.B. Ch.B
Phone
22553303/ 97018342
Email
mgirwin@hku.hk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Micheal Garnet Irwin, M.B. Ch.B
Organizational Affiliation
The University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
HKU Li Ka Shing Faculty of Medicine
City
Hong Kong
State/Province
Guangdong
ZIP/Postal Code
999077
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chong
Phone
(852)22553749

12. IPD Sharing Statement

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Intranasal Dexmedetomidine and Zolpidem for Treatment of Primary Insomnia

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