The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study

Anelia Dietmann; Elena Wenz; Julia van der Meer; Maya Ringli; Jan D Warncke; Ellen Edwards; Markus H Schmidt; Corrado A Bernasconi; Arto Nirkko; Mathias Strub; Silvia Miano; Mauro Manconi; Jens Acker; Sigrid von Manitius; Christian R Baumann; Philip O Valko; Bahtiyar Yilmaz; Andreas-David Brunner; Athina Tzovara; Zhongxing Zhang; Carlo R Largiadèr; Mehdi Tafti; Daniela Latorre; Federica Sallusto; Ramin Khatami; Claudio L A Bassetti

doi:10.1111/jsr.13296

The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study

J Sleep Res. 2021 Oct;30(5):e13296. doi: 10.1111/jsr.13296. Epub 2021 Apr 4.

Authors

Anelia Dietmann¹, Elena Wenz^{1

2}, Julia van der Meer¹, Maya Ringli¹, Jan D Warncke¹, Ellen Edwards¹, Markus H Schmidt¹, Corrado A Bernasconi¹, Arto Nirkko³, Mathias Strub⁴, Silvia Miano⁵, Mauro Manconi⁵, Jens Acker⁶, Sigrid von Manitius⁷, Christian R Baumann⁸, Philip O Valko⁸, Bahtiyar Yilmaz^{9

10}, Andreas-David Brunner¹¹, Athina Tzovara^{12

13

14}, Zhongxing Zhang¹⁵, Carlo R Largiadèr¹⁶, Mehdi Tafti¹⁷, Daniela Latorre¹⁸, Federica Sallusto^{18

19}, Ramin Khatami^{1

15}, Claudio L A Bassetti¹

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
² Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
³ Neurozentrum Luzern, Luzern, Switzerland.
⁴ Zentrum für Schlafmedizin Basel, Basel, Switzerland.
⁵ Sleep and Epilepsy Center, Neurocenter of the Southern Switzerland, Regional Hospital (EOC) of Lugano, Lugano, Switzerland.
⁶ Clinic for Sleep Medicine, Bad Zurzach, Switzerland.
⁷ Department of Neurology, Kantonsspital St. Gallen St, Gallen, Switzerland.
⁸ Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
⁹ Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁰ Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland.
¹¹ Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
¹² Institute of Computer Science, University of Bern, Bern, Switzerland.
¹³ Department of Neurology, Sleep Wake Epilepsy Center, NeuroTec, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁴ Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
¹⁵ Clinic Barmelweid, Center for Sleep Medicine and Sleep Research, Barmelweid, Switzerland.
¹⁶ Department of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
¹⁷ Department of Biomedical Science, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
¹⁸ Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
¹⁹ Institute for Research in Biomedicine, Faculty of Biomedical Sciences, USI, Bellinzona, Switzerland.

Abstract

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH.

Trial registration: ClinicalTrials.gov NCT04330963.

Keywords: biomarkers; electrophysiology; excessive daytime sleepiness; hypersomnia; sleep-wake disorders.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Disorders of Excessive Somnolence* / diagnosis
Disorders of Excessive Somnolence* / etiology
Disorders of Excessive Somnolence* / therapy
Humans
Multicenter Studies as Topic
Narcolepsy* / diagnosis
Narcolepsy* / therapy
Observational Studies as Topic
Prospective Studies
Switzerland

Associated data

ClinicalTrials.gov/NCT04330963