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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05303935




Registration number
NCT05303935
Ethics application status
Date submitted
24/02/2022
Date registered
31/03/2022
Date last updated
6/07/2023

Titles & IDs
Public title
Effects of Quetiapine on Sleep and Next Day Alertness in People With Obstructive Sleep Apnea
Scientific title
Effects of Quetiapine on Sleep and Next Day Alertness in People With Obstructive Sleep Apnea
Secondary ID [1] 0 0
4965
Universal Trial Number (UTN)
Trial acronym
QOSA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sleep Apnea, Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Quetiapine 50 MG
Treatment: Drugs - Placebo

Experimental: Quetiapine - Quetiapine 50mg in the form of one capsule, taken before bedtime. Dosage is taken on one instance for one night only.

Placebo comparator: Placebo - Placebo sugar pill in the form of one capsule, taken before bedtime. Dosage is taken on one instance for one night only.


Treatment: Drugs: Quetiapine 50 MG
A single dose of 50mg of quetiapine taken at bedtime for one night.

Treatment: Drugs: Placebo
A placebo sugar pill that looks like the quetiapine tablet taken at bedtime for one night.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in OSA severity (Quetiapine night vs. placebo night)
Timepoint [1] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [1] 0 0
Change in nadir overnight hypoxemia (Quetiapine night vs. placebo night)
Timepoint [1] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [2] 0 0
Change in mean overnight hypoxemia (Quetiapine night vs. placebo night)
Timepoint [2] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [3] 0 0
Change in time below 90% blood arterial oxygen saturation (Quetiapine night vs. placebo night)
Timepoint [3] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [4] 0 0
Change in sleep efficiency (Quetiapine night vs. placebo night)
Timepoint [4] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [5] 0 0
Change in arousal index (Quetiapine night vs. placebo night)
Timepoint [5] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [6] 0 0
Change in sleep architecture (Quetiapine night vs. placebo night)
Timepoint [6] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [7] 0 0
Change in respiratory control (Quetiapine night vs. placebo night)
Timepoint [7] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [8] 0 0
Change in the respiratory arousal threshold (Quetiapine night vs. placebo night)
Timepoint [8] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [9] 0 0
Change in airway collapsibility (Quetiapine night vs. placebo night)
Timepoint [9] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [10] 0 0
Change in pharyngeal muscle response (Quetiapine night vs. placebo night)
Timepoint [10] 0 0
Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [11] 0 0
Baseline OSA endotypes (outcomes 8-11) and whether they are associated with changes in OSA severity (Quetiapine night vs. placebo night)
Timepoint [11] 0 0
Baseline sleep study
Secondary outcome [12] 0 0
Change in perceived sleepiness (Quetiapine night vs. placebo night)
Timepoint [12] 0 0
Next morning following two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [13] 0 0
Change in driving simulator performance (Quetiapine night vs. placebo night)
Timepoint [13] 0 0
Next morning following two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.
Secondary outcome [14] 0 0
Change in psycho-motor vigilance (Quetiapine night vs. placebo night)
Timepoint [14] 0 0
Next morning following two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.

Eligibility
Key inclusion criteria
* Ages: 18+ (Adult, Older Adult)
* Gender: All
* Moderate or more "difficulty staying asleep" score on the Insomnia Severity Index questionnaire
* Obstructive Sleep Apnoea (OSA), Apnoea Hypopnea Index = 5 events/hour
* BMI between 18.5 and 40 kg/m2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Concomitant medications that interact or are contraindicated with quetiapine
* Concomitant medications known to influence breathing, sleep, arousal, or muscle physiology
* Current pregnancy or breast-feeding
* Current or recent other medical conditions likely to affect results or safety

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/04/2023
Sample size
Target
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Adelaide Institute for Sleep Health - Adelaide
Recruitment postcode(s) [1] 0 0
5042 - Adelaide

Funding & Sponsors
Primary sponsor type
Other
Name
Flinders University
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Quetiapine is medication used to treat schizophrenia and bipolar disorder. Increasingly, low doses of quetiapine are prescribed "off-label" for insomnia. Quetiapine increases sleep duration with fewer interruptions, and people report feeling more rested. This accounts for why it is popular to prescribe for insomnia. Insomnia and obstructive sleep apnea (OSA) share many symptoms and differential diagnosis can be difficult. While quetiapine may improve sleep and breathing in certain people (i.e in light sleepers) an initial study indicated that quetiapine caused breathing disturbances in healthy individuals. Effects in OSA are unknown. In this placebo-controlled double blind study, participants with mild-moderate OSA will spend 2 nights in the sleep lab, one with quetiapine at a dose commonly prescribed for insomnia and one with placebo. The investigators will assess participants sleep by standard clinical sleep study, and morning alertness using questionnaires, reaction tests, and a driving simulator test.
Trial website
https://clinicaltrials.gov/study/NCT05303935
Trial related presentations / publications
Debernard KAB, Frost J, Roland PH. Quetiapine is not a sleeping pill. Tidsskr Nor Laegeforen. 2019 Sep 16;139(13). doi: 10.4045/tidsskr.19.0205. Print 2019 Sep 24. English, Norwegian.
McKean A, Monasterio E, Elliott T. How common is off-label prescription of quetiapine? N Z Med J. 2018 Oct 26;131(1484):77-78. No abstract available.
Pringsheim T, Gardner DM. Dispensed prescriptions for quetiapine and other second-generation antipsychotics in Canada from 2005 to 2012: a descriptive study. CMAJ Open. 2014 Oct 1;2(4):E225-32. doi: 10.9778/cmajo.20140009. eCollection 2014 Oct.
Cohrs S, Rodenbeck A, Guan Z, Pohlmann K, Jordan W, Meier A, Ruther E. Sleep-promoting properties of quetiapine in healthy subjects. Psychopharmacology (Berl). 2004 Jul;174(3):421-9. doi: 10.1007/s00213-003-1759-5. Epub 2004 Mar 17.
Karsten J, Hagenauw LA, Kamphuis J, Lancel M. Low doses of mirtazapine or quetiapine for transient insomnia: A randomised, double-blind, cross-over, placebo-controlled trial. J Psychopharmacol. 2017 Mar;31(3):327-337. doi: 10.1177/0269881116681399. Epub 2017 Jan 16.
Meira E Cruz M, Kryger MH, Morin CM, Palombini L, Salles C, Gozal D. Comorbid Insomnia and Sleep Apnea: mechanisms and implications of an underrecognized and misinterpreted sleep disorder. Sleep Med. 2021 Aug;84:283-288. doi: 10.1016/j.sleep.2021.05.043. Epub 2021 Jun 8.
Sweetman A, Lack L, McEvoy RD, Smith S, Eckert DJ, Osman A, Carberry JC, Wallace D, Nguyen PD, Catcheside P. Bi-directional relationships between co-morbid insomnia and sleep apnea (COMISA). Sleep Med Rev. 2021 Dec;60:101519. doi: 10.1016/j.smrv.2021.101519. Epub 2021 Jun 23.
Benjafield AV, Ayas NT, Eastwood PR, Heinzer R, Ip MSM, Morrell MJ, Nunez CM, Patel SR, Penzel T, Pepin JL, Peppard PE, Sinha S, Tufik S, Valentine K, Malhotra A. Estimation of the global prevalence and burden of obstructive sleep apnoea: a literature-based analysis. Lancet Respir Med. 2019 Aug;7(8):687-698. doi: 10.1016/S2213-2600(19)30198-5. Epub 2019 Jul 9.
Eckert DJ. Phenotypic approaches to obstructive sleep apnoea - New pathways for targeted therapy. Sleep Med Rev. 2018 Feb;37:45-59. doi: 10.1016/j.smrv.2016.12.003. Epub 2016 Dec 18.
Eckert DJ, White DP, Jordan AS, Malhotra A, Wellman A. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med. 2013 Oct 15;188(8):996-1004. doi: 10.1164/rccm.201303-0448OC.
Carter SG, Eckert DJ. Effects of hypnotics on obstructive sleep apnea endotypes and severity: Novel insights into pathophysiology and treatment. Sleep Med Rev. 2021 Aug;58:101492. doi: 10.1016/j.smrv.2021.101492. Epub 2021 Apr 22.
Eckert DJ, Owens RL, Kehlmann GB, Wellman A, Rahangdale S, Yim-Yeh S, White DP, Malhotra A. Eszopiclone increases the respiratory arousal threshold and lowers the apnoea/hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold. Clin Sci (Lond). 2011 Jun;120(12):505-14. doi: 10.1042/CS20100588.
Khazaie H, Sharafkhaneh A, Khazaie S, Ghadami MR. A weight-independent association between atypical antipsychotic medications and obstructive sleep apnea. Sleep Breath. 2018 Mar;22(1):109-114. doi: 10.1007/s11325-017-1537-y. Epub 2017 Jul 13.
Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999 Aug 1;22(5):667-89. No abstract available.
Public notes

Contacts
Principal investigator
Name 0 0
Danny Eckert, PhD
Address 0 0
Flinders University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05303935