Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS)

• ClinicalTrials.gov Identifier: NCT04330963
• Recruitment Status: Recruiting
• First Posted: April 2, 2020
• Last Update Posted: May 23, 2022
• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Klinik Barmelweid; Zentrum für Schlafmedizin Basel; Ospedale Regionale di Lugano; Cantonal Hospital of St. Gallen; Zurzach Care Klinik für Schlafmedizin; University Children's Hospital, Zurich; University Children's Hospital Basel; Centre Lausannios de Sommeil
• Information provided by (Responsible Party): University Hospital Inselspital, Berne

Study Description

Brief Summary:

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.

Condition or disease
Narcolepsy; Idiopathic Hypersomnia; Hypersomnolence Disorder

Detailed Description:

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

Study Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 600 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 36 Months
• Official Title: Swiss Primary Hypersomnolence and Narcolepsy Cohort Study
• Actual Study Start Date: January 6, 2020
• Estimated Primary Completion Date: December 30, 2024
• Estimated Study Completion Date: June 30, 2026

Groups and Cohorts

Group/Cohort
Hypersomnolence group; 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; Healthy control subjects without complaints of EDS and /or H.
SDB controls; Patients with EDS and diagnosis of severe sleep related breathing disorder (SBD) significantly improving with therapy.
Pediatric Hypersomnolence group; Pediatric group aged 10-18. Same criteria for inclusion and exclusion apply as for the adult group.

Outcome Measures

Primary Outcome Measures :

1. Proportion of study subjects with diagnosis of Narcolepsy type 1 (NT1) at follow up [ Time Frame: 36 months ]
2. Proportion of study subjects with final diagnosis other than NT1 but within the group of CDH at follow up [ Time Frame: 36 months ]

Secondary Outcome Measures :

1. Proportion of patients with autoreactive T-cell clones in NT1 and some Narcolepsy borderland (NBL) subjects but not in controls [ Time Frame: 36 months ]
2. Preptidomic profile of NT1 and NBL in comparison to controls [ Time Frame: 36 months ]
   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
3. Gut microbiome of NT1 and NBL in comparison to controls [ Time Frame: 36 months ]
   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

Biospecimen Retention:   Samples With DNA

Blood cerebrospinal fluid (CSF) Stool

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

The project population consists of subjects, who were referred to the outpatient clinic / sleep center of one of the study sites for further investigation, due to complaints of EDS and / or H and / or suspected Central disorders of hypersomnolence (CDH), fulfilling inclusion / exclusion criteria and a control population as well as healthy controls.

Criteria

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

Contacts and Locations

Contacts

Contact: Claudio L Bassetti, Prof.; +41 31 63 2 30 66 ext +41316323066; Claudio.Bassetti@insel.ch

Contact: Jan Warncke, PhD; +41 31 66 4 07 99; jan.warncke@insel.ch

Locations

Switzerland

Claudio L Bassetti; Recruiting

Bern, Switzerland, 3010

Contact: Claudio L Bassetti, Prof +41316323066 ext +41316323066 Claudio.Bassetti@insel.ch

Contact: Jan Warncke, PhD +41 31 664 07 99 jan.warncke@insel.ch

Sponsors and Collaborators

University Hospital Inselspital, Berne

Klinik Barmelweid

Zentrum für Schlafmedizin Basel

Ospedale Regionale di Lugano

Cantonal Hospital of St. Gallen

Zurzach Care Klinik für Schlafmedizin

University Children's Hospital, Zurich

University Children's Hospital Basel

Centre Lausannios de Sommeil

Investigators

• Study Director: Claudio L Bassetti, Prof.; Insel Gruppe

More Information

Publications:

Bassetti CLA, Adamantidis A, Burdakov D, Han F, Gay S, Kallweit U, Khatami R, Koning F, Kornum BR, Lammers GJ, Liblau RS, Luppi PH, Mayer G, Pollmächer T, Sakurai T, Sallusto F, Scammell TE, Tafti M, Dauvilliers Y. Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nat Rev Neurol. 2019 Sep;15(9):519-539. doi: 10.1038/s41582-019-0226-9. Epub 2019 Jul 19. Review.

Latorre D, Kallweit U, Armentani E, Foglierini M, Mele F, Cassotta A, Jovic S, Jarrossay D, Mathis J, Zellini F, Becher B, Lanzavecchia A, Khatami R, Manconi M, Tafti M, Bassetti CL, Sallusto F. T cells in patients with narcolepsy target self-antigens of hypocretin neurons. Nature. 2018 Oct;562(7725):63-68. doi: 10.1038/s41586-018-0540-1. Epub 2018 Sep 19.

Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain. 1997 Aug;120 ( Pt 8):1423-35.

Dietmann A, Wenz E, van der Meer J, Ringli M, Warncke JD, Edwards E, Schmidt MH, Bernasconi CA, Nirkko A, Strub M, Miano S, Manconi M, Acker J, von Manitius S, Baumann CR, Valko PO, Yilmaz B, Brunner AD, Tzovara A, Zhang Z, Largiadèr CR, Tafti M, Latorre D, Sallusto F, Khatami R, Bassetti CLA. 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.

• Responsible Party: University Hospital Inselspital, Berne
• ClinicalTrials.gov Identifier: NCT04330963
• Other Study ID Numbers: 2019-00788
• First Posted: April 2, 2020
• Last Update Posted: May 23, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Narcolepsy; Disorders of Excessive Somnolence; Idiopathic Hypersomnia; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders