Effects of Quetiapine on Sleep and Next Day Alertness in People With Obstructive Sleep Apnea

NCT05303935 | Completed Phase 2

• 1 other identifier: 4965
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Sleep Apnea, Obstructive

Keywords

Sleep apnea, obstructive; quetiapine; randomised; double-blind; placebo; respiratory arousal threshold

Outcome Measures

Primary Outcomes (1)

• Change in OSA severity (Quetiapine night vs. placebo night)

  OSA severity as measured by the AHI (apnoea hypopnea index measured as # events/h sleep) during overnight in-laboratory polysomnography.

  Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.

Secondary Outcomes (14)

• Change in nadir overnight hypoxemia (Quetiapine night vs. placebo night)

  Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.

• Change in mean overnight hypoxemia (Quetiapine night vs. placebo night)

  Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.

• Change in time below 90% blood arterial oxygen saturation (Quetiapine night vs. placebo night)

  Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.

• Change in sleep efficiency (Quetiapine night vs. placebo night)

  Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.

• Change in arousal index (Quetiapine night vs. placebo night)

  Two non-consecutive single night sleep studies (Quetiapine night vs. placebo night) up to one month apart.

Study Arms (2)

Quetiapine

EXPERIMENTAL

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

Drug: Quetiapine 50 MG

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Quetiapine 50 MG DRUG

A single dose of 50mg of quetiapine taken at bedtime for one night.

Also known as: Seroquel

Quetiapine

Placebo DRUG

A placebo sugar pill that looks like the quetiapine tablet taken at bedtime for one night.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Flinders University: lead

Study Sites (1)

Adelaide Institute for Sleep Health

Adelaide, South Australia, 5042, Australia

Location

Related Publications (14)

• 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.

  PMID: 31556541 BACKGROUND

• 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.

  PMID: 30359361 BACKGROUND

• 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.

  PMID: 25485247 BACKGROUND

• 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.

  PMID: 15029469 BACKGROUND

• 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.

  PMID: 28093029 BACKGROUND

• 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.

  PMID: 34214960 BACKGROUND

• 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.

  PMID: 34229295 BACKGROUND

• 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.

  PMID: 31300334 BACKGROUND

• 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.

  PMID: 28110857 BACKGROUND

• 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.

  PMID: 23721582 BACKGROUND

• 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.

  PMID: 33965721 BACKGROUND

• 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.

  PMID: 21269278 BACKGROUND

• 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.

  PMID: 28707161 BACKGROUND

• 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.

  PMID: 10450601 BACKGROUND

Related Links

• Compendium EM. SEROQUEL 25 mg film-coated tablets. 2021 \[cited 2021 22/10/2021\].
• AstraZeneca. Australian Product Information Seroquel. 2020.

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Quetiapine Fumarate; Sugars

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbohydrates

Study Officials

• Danny Eckert, PhD

  Flinders University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Adelaide Institute for Sleep Health

Model Details: Double-blind, randomized, placebo-controlled, cross-over study

Study Record Dates

• First Submitted: February 24, 2022
• First Posted: March 31, 2022
• Study Start: May 25, 2022
• Primary Completion: April 4, 2023
• Study Completion: April 4, 2023
• Last Updated: July 6, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: At conclusion of study and related publications.
• Access Criteria: IPD may be shared for research purposes on application to the chief investigator and subject to applicable ethical review.

Locations

AU (1)