Clinical trial NCT04330963: International Swiss Primary Hypersomnolence and Narcolepsy Cohort Study
Official title: International Swiss Primary Hypersomnolence and Narcolepsy Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Narcolepsy
Idiopathic Hypersomnia
Hypersomnolence Disorder
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Klinik Barmelweid
name: Zentrum für Schlafmedizin Basel
name: Ospedale Regionale di Lugano
name: Cantonal Hospital of St. Gallen
name: Zurzach Care Klinik für Schlafmedizin
name: University Children's Hospital, Zurich
name: University Children's Hospital Basel
name: Centre Lausannios de Sommeil
name: Private Universität Witten-Herdecke and Orfea Fachklinik für Schlafmedizin, Witten, Germany
name: Leiden University Medical Center, Leiden, Netherlands
name: University of Bologna, Bologna, Italy
First posted: 2020-04-02
Enrollment: 600
Sex: ALL
Minimum age (years): 10
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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

Eligibility 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

Primary outcomes:
measure: Proportion of study subjects with diagnosis of Narcolepsy type 1 (NT1) at follow up
timeFrame: 36 months
measure: Proportion of study subjects with final diagnosis other than NT1 but within the group of CDH at follow up
timeFrame: 36 months
Secondary outcomes:
measure: Proportion of patients with autoreactive T-cell clones in NT1 and some Narcolepsy borderland (NBL) subjects but not in controls
timeFrame: 36 months
measure: Preptidomic profile of NT1 and NBL in comparison to controls
timeFrame: 36 months
measure: Gut microbiome of NT1 and NBL in comparison to controls
timeFrame: 36 months
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Claudio L Bassetti
Study officials:
affiliation: Insel Gruppe
name: Claudio L Bassetti, Prof.
role: STUDY_DIRECTOR
References:
citation: 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, Pollmacher 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.
citation: 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.
citation: Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain. 1997 Aug;120 ( Pt 8):1423-35. doi: 10.1093/brain/120.8.1423.
citation: 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, Largiader 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.