International Swiss Primary Hypersomnolence and Narcolepsy Cohort Study

Narcolepsy Clinical Trial

— iSPHYNCS  

Official title:

International Swiss Primary Hypersomnolence and Narcolepsy Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04330963
• Other study ID #: 2019-00788
• Status: Recruiting
• Start date: January 6, 2020
• Est. completion date: June 30, 2026

Study information

• Verified date: April 2023
• Source: University Hospital Inselspital, Berne
• Contact: Claudio L Bassetti, Prof.
• Phone: +41 31 63 2 30 66
• Email: Claudio.Bassetti[@]insel.ch
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: June 30, 2026
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Disorders of Excessive Somnolence
• Hypersomnolence Disorder
• Idiopathic Hypersomnia
• Narcolepsy

Locations

Country	Name	City	State
Switzerland	Claudio L Bassetti	Bern

Sponsors (12)

Lead Sponsor

Collaborator

University Hospital Inselspital, Berne

Cantonal Hospital of St. Gallen, Centre Lausannios de Sommeil, Klinik Barmelweid, Leiden University Medical Center, Leiden, Netherlands, Ospedale Regionale di Lugano, Private Universität Witten-Herdecke and Orfea Fachklinik für Schlafmedizin, Witten, Germany, University Children's Hospital Basel, University Children's Hospital, Zurich, University of Bologna, Bologna, Italy, Zentrum für Schlafmedizin Basel, Zurzach Care Klinik für Schlafmedizin

Country where clinical trial is conducted

Switzerland, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of study subjects with diagnosis of Narcolepsy type 1 (NT1) at follow up		36 months
Primary	Proportion of study subjects with final diagnosis other than NT1 but within the group of CDH at follow up		36 months
Secondary	Proportion of patients with autoreactive T-cell clones in NT1 and some Narcolepsy borderland (NBL) subjects but not in controls		36 months
Secondary	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
Secondary	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