The Role of the Circadian System in Neurological Sleep-wake Disorders

Idiopathic Hypersomnia Clinical Trial

— PNP  

Official title:

The Role of the Circadian System in Neurological Sleep-wake Disorders: Assessment of Circadian and Homeostatic Sleep-wake Regulation and Vigilance With a Poly-nap Protocol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03356938
• Other study ID #: CHPNP2016
• Status: Completed
• Phase: N/A
• Start date: November 28, 2017
• Est. completion date: May 31, 2020

Study information

• Verified date: February 2021
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to investigate the role of the circadian system in patients with neurologic sleep-wake disorders. Therefore, overnight sleep will be distributed over 30 hours into repetitive sleep-wake cycles (poly-nap protocol), so that sleep episodes occur at different circadian phases. Vigilance, attention, risk behavior as well as sleep onset latency will be observed.

Ambulatory accelerometer recordings gain more and more attention in the diagnostic work-up of sleep disorders, as they allow to also include the everyday rest-activity rhythm before examinations in the sleep laboratory. Advances of novel devices should improve the detection of rest and activity and therefore the estimation of sleep and wake, especially in patients with neurologic sleep-wake disorders exhibiting fragmented sleep. Two types of actimeters will be applied throughout our study protocol to explore better classification of sleep and wake phases and patterns of the rest-activity rhythm.

This study is designed as an observational case-controlled study targeting the disorders of narcolepsy type 1 and idiopathic hypersomnia, and including interventional procedures in the healthy control group (sleep deprivation, sleep restriction) in a counter-balanced design.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 31, 2020
• Est. primary completion date: May 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Male and Female participants 18 years to 35 years of age

• Written informed consent by the participant after information about the research project

• Healthy controls: 7-8 hours of sleep per night

• Healthy controls: sleep satiation before start of the study

• Narcolepsy type 1: diagnosis of narcolepsy with cataplexy, drug free during study, proven excessive daytime sleepiness with increased REM (MSLT), clear-cut cataplexy present, undetectable or low cerebrospinal fluid hypocretin levels (if data is available)

• Idiopathic hypersomnia: diagnosis of idiopathic hypersomnia, drug free during study, proven excessive daytime sleepiness without increased REM (MSLT), increased sleep need (>10h/day) on work-free days shown by 2-week actigraphy

Exclusion Criteria:

• signs of neurological, psychiatric, or other sleep-wake disorders

• signs of sleep deprivation

• shift work and time zone change of more than one hour within one month prior the study start

• extreme morning and evening types

• underweight

• obstructive gastro-intestinal disease or history of gastrointestinal surgery

• an implanted medical device or a scheduled MRI scan during the experimental period

Related Conditions & MeSH terms

• Disorders of Excessive Somnolence
• Idiopathic Hypersomnia
• Narcolepsy
• Narcolepsy 1
• Sleep Wake Disorders

Intervention

Behavioral:
• Sleep restriction
Restricted sleep to 5 hours / night for 5 days prior to sleep laboratory examination
• Sleep deprivation
Sleep deprivation during first night of sleep laboratory examination

Locations

Country	Name	City	State
Switzerland	University Hospital Zurich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Esther Werth

Country where clinical trial is conducted

Switzerland, 

References & Publications (7)

Borbély AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1(3):195-204. — View Citation

Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. 2007 Feb 10;369(9560):499-511. Review. — View Citation

Frenette E, Kushida CA. Primary hypersomnias of central origin. Semin Neurol. 2009 Sep;29(4):354-67. doi: 10.1055/s-0029-1237114. Epub 2009 Sep 9. Review. — View Citation

Morgenthaler T, Alessi C, Friedman L, Owens J, Kapur V, Boehlecke B, Brown T, Chesson A Jr, Coleman J, Lee-Chiong T, Pancer J, Swick TJ; Standards of Practice Committee; American Academy of Sleep Medicine. Practice parameters for the use of actigraphy in the assessment of sleep and sleep disorders: an update for 2007. Sleep. 2007 Apr;30(4):519-29. — View Citation

Münch M, Knoblauch V, Blatter K, Schröder C, Schnitzler C, Kräuchi K, Wirz-Justice A, Cajochen C. Age-related attenuation of the evening circadian arousal signal in humans. Neurobiol Aging. 2005 Oct;26(9):1307-19. Epub 2005 Apr 18. — View Citation

Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005 Oct 27;437(7063):1257-63. Review. — View Citation

Wulff K, Gatti S, Wettstein JG, Foster RG. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat Rev Neurosci. 2010 Aug;11(8):589-99. doi: 10.1038/nrn2868. Epub 2010 Jul 14. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endogenous melatonin	Dim light melatonin onset (DLMO) will show whether there is a phase difference between patient groups and between patients and controls. The amplitude of the melatonin profile will show whether there is a dampening of the circadian rhythm or not.	Half an hour before and half an hour after a nap during PNP protocol, up to 2 minutes.
Primary	EEG slow-wave activity (SWA)	SWA is a marker of homeostatic sleep pressure and will show whether patients with narcolepsy or idiopathic hypersomnia live under different sleep pressure than controls.	Over nap times, up to 80 minutes.
Secondary	Performance in neurobehavioral tests	Outcome for vigilance and cognition of the subjects.	One hour before each nap, up to 45mins.
Secondary	EEG event related potentials (ERPs)		One hour before each nap, up to 45minutes.