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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Narcolepsy 1, Idiopathic Hypersomnia

Intervention / Treatment
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* Behavioral: Sleep restriction
* Behavioral: Sleep deprivation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Baseline recording<br> | |
| Experimental: Sleep restriction<br> | Behavioral: Sleep restriction<br>* Restricted sleep to 5 hours / night for 5 days prior to sleep laboratory examination<br>|
| Experimental: Sleep deprivation<br> | Behavioral: Sleep deprivation<br>* Sleep deprivation during first night of sleep laboratory examination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Performance in neurobehavioral tests | Outcome for vigilance and cognition of the subjects. | One hour before each nap, up to 45mins. | 
| EEG event related potentials (ERPs) |  | One hour before each nap, up to 45minutes. |