Clinical trial NCT03356938: The Role of the Circadian System in Neurological Sleep-wake Disorders
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Narcolepsy 1
Idiopathic Hypersomnia
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2017-11-29
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Endogenous melatonin
timeFrame: Half an hour before and half an hour after a nap during PNP protocol, up to 2 minutes.
measure: EEG slow-wave activity (SWA)
timeFrame: Over nap times, up to 80 minutes.
Secondary outcomes:
measure: Performance in neurobehavioral tests
timeFrame: One hour before each nap, up to 45mins.
measure: EEG event related potentials (ERPs)
timeFrame: One hour before each nap, up to 45minutes.
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University of Zurich
name: Esther Werth, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Borbely AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1(3):195-204. No abstract available.
citation: Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. 2007 Feb 10;369(9560):499-511. doi: 10.1016/S0140-6736(07)60237-2.
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.
citation: Munch M, Knoblauch V, Blatter K, Schroder C, Schnitzler C, Krauchi 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. doi: 10.1016/j.neurobiolaging.2005.03.004. Epub 2005 Apr 18.
citation: Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005 Oct 27;437(7063):1257-63. doi: 10.1038/nature04284.
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.
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. doi: 10.1093/sleep/30.4.519.