International Swiss Primary Hypersomnolence and Narcolepsy Cohort Study

Study Overview
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Brief Summary
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Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a cohort study on disease presentation and long-term course with an exploratory approach to detect biomarkers.

Detailed Description
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An exploratory prospective, national, multi-center cohort study on clinical, electrophysiological and biological biomarkers of disease presentation and course.

Official Title
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International Swiss Primary Hypersomnolence and Narcolepsy Cohort Study

Conditions
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Narcolepsy, Idiopathic Hypersomnia, Hypersomnolence Disorder

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participants: Subjective complaints of Excessive daytime sleepiness (EDS) and/or Hypersomnia (H) as defined above EDS and/or H present daily or almost daily for at least 1 month prior to the consultation Ability and consent to undergo electrophysiological routine assessment Ability to give informed consent Healthy controls: Age and gender matched healthy subjects Including blood related relatives of study participants Ability and consent to undergo electrophysiological routine assessment Ability to give informed consent Controls with Sleep disordered breathing (SDB): Subjective complaints of EDS with Epworth Sleepiness Scale (ESS) > 10 (adults) and/or H due to SDB: Presence of clinically significant and untreated obstructive sleep apnea (OSA) as determined by the investigator with an apnea-hypopnea-index >30/h Multiple sleep-latency test (MSLT) mean sleep latency ≤ 8min Subjective and objective improvement of EDS and/or H within 3 months after treatment with Positive airway pressure (PAP) therapy with documented Reduction of apnea-hypopnea index below <10/h Reduction of ESS by ≥ 25% MSLT mean Sleep Latency > 12min Ability and consent to undergo electrophysiological routine assessment Ability to give informed consent Exclusion Criteria: Study participants and controls: SDB for study participants and healthy controls: Presence of clinically significant and untreated obstructive sleep apnea (OSA) or central sleep apnea (CSA) as determined by the investigator or documented previously; or documentation of one of the following: Apnea index (AI) > 10 if on OSA treatment or untreated; or Clinically significant hypoventilation; or Noncompliance with primary OSA therapy except if NT1 has been diagnosed including decreased or missing cerebrospinal fluid (CSF) hypocretin SDB for control population with SDB: Central Sleep Apnea (CSA) Noncompliance with primary OSA therapy and/or No reported improvement of EDS and/or H within 3 months of positive airway pressure (PAP) treatment The following disorders/conditions that on clinical grounds are considered to be the cause of EDS / H Other sleep disorders (e.g. Restless legs syndrome (RLS) with periodic leg movement syndrome (PLMS), sleepwalking, clear-cut circadian disorder) Other neurological disorders (e.g. stroke, multiple sclerosis, parkinsonism, severe traumatic brain injury) (Auto-)immune and systemic disorders (such as Hashimoto Thyroiditis, Chron's Disease, ulcerous colitis, Diabetes mellitus type I, Systemic lupus erythematosus) Malignancy (except: Status in Remission for at least > 10 years) Instable psychiatric disorder (e.g. acute psychotic, acute suicidal, episode of major depression requiring in-hospital treatment, active substance abuse) Active infectious disease at screening Permanent medications / drugs Chronic infectious diseases (such as Hepatitis B/C, HIV) Chronic use of antibiotics Recent use (< 8 weeks) of immune-modulating drugs Healthy controls additional: Subjective complaints of EDS and / or H ESS > 10 Polysomnography (PSG) with AI > 10/h and / or PLMS Index > 30/h MSLT mean Sleep Latency < 12 min

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 70 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hypersomnolence group<br>All patients referred to the outpatient clinic/sleep center for investigation due to complaints for excessive daytime sleepiness (EDS) and/or Hypersomnia (H) and/or suspected central disorder of hypersomnolence (CDH) | |
| Healthy controls<br>Healthy control subjects without complaints of EDS and /or H. | |
| SDB controls<br>Patients with EDS and diagnosis of severe sleep related breathing disorder (SBD) significantly improving with therapy. | |
| Pediatric Hypersomnolence group<br>Pediatric group aged 10-18. Same criteria for inclusion and exclusion apply as for the adult group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of study subjects with diagnosis of Narcolepsy type 1 (NT1) at follow up |  | 36 months | 
| Proportion of study subjects with final diagnosis other than NT1 but within the group of CDH at follow up |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with autoreactive T-cell clones in NT1 and some Narcolepsy borderland (NBL) subjects but not in controls |  | 36 months | 
| Preptidomic profile of NT1 and NBL in comparison to controls | Mass spectrometry based peptidomics of cerebrospinal fluid (CSF) for the identification of Hypocretin and approximately 6000 other neuropeptides in 10 to 20 samples for each group to be analyzed. In collaboration with the group of Prof. Matthias Mann, Max Planck Institute of Biochemistry, Planegg, Germany | 36 months | 
| Gut microbiome of NT1 and NBL in comparison to controls | 16S based analysis of the gut microbiome based on stool samples from all participants (where available). In collaboration with the group of Prof. Andrew Macpherson, University of Bern | 36 months |