The Role of the Circadian System in Neurological Sleep-wake Disorders (PNP)
Primary Purpose
Narcolepsy 1, Idiopathic Hypersomnia
Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Sleep restriction
Sleep deprivation
Sponsored by
About this trial
This is an interventional basic science trial for Narcolepsy 1
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
Sites / Locations
- University Hospital Zurich
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Experimental
Experimental
Arm Label
Baseline recording
Sleep restriction
Sleep deprivation
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Performance in neurobehavioral tests
Outcome for vigilance and cognition of the subjects.
EEG event related potentials (ERPs)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03356938
Brief Title
The Role of the Circadian System in Neurological Sleep-wake Disorders
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
November 28, 2017 (Actual)
Primary Completion Date
May 31, 2019 (Actual)
Study Completion Date
May 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Esther Werth
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Narcolepsy 1, Idiopathic Hypersomnia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Baseline recording
Arm Type
No Intervention
Arm Title
Sleep restriction
Arm Type
Experimental
Arm Title
Sleep deprivation
Arm Type
Experimental
Intervention Type
Behavioral
Intervention Name(s)
Sleep restriction
Intervention Description
Restricted sleep to 5 hours / night for 5 days prior to sleep laboratory examination
Intervention Type
Behavioral
Intervention Name(s)
Sleep deprivation
Intervention Description
Sleep deprivation during first night of sleep laboratory examination
Primary Outcome Measure Information:
Title
Endogenous melatonin
Description
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.
Time Frame
Half an hour before and half an hour after a nap during PNP protocol, up to 2 minutes.
Title
EEG slow-wave activity (SWA)
Description
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.
Time Frame
Over nap times, up to 80 minutes.
Secondary Outcome Measure Information:
Title
Performance in neurobehavioral tests
Description
Outcome for vigilance and cognition of the subjects.
Time Frame
One hour before each nap, up to 45mins.
Title
EEG event related potentials (ERPs)
Time Frame
One hour before each nap, up to 45minutes.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Esther Werth, PhD
Organizational Affiliation
University of Zurich
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Zurich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
7185792
Citation
Borbely AA. A two process model of sleep regulation. Hum Neurobiol. 1982;1(3):195-204. No abstract available.
Results Reference
background
PubMed Identifier
17292770
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.
Results Reference
background
PubMed Identifier
19742411
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.
Results Reference
background
PubMed Identifier
16182904
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.
Results Reference
background
PubMed Identifier
16251950
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.
Results Reference
background
PubMed Identifier
20631712
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.
Results Reference
background
PubMed Identifier
17520797
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.
Results Reference
background
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The Role of the Circadian System in Neurological Sleep-wake Disorders
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