SPHYNCS: Swiss Primary Hypersomnolence and Narcolepsy Cohort Study
Study Details
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 | Intervention/Treatment | Phase |
|---|---|---|
|
|
Detailed Description
An exploratory prospective, national, multi-center cohort study on clinical, electrophysiological and biological biomarkers of disease presentation and course.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
- 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
- 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 [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
- Gut microbiome of NT1 and NBL in comparison to controls [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
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Claudio L Bassetti | Bern | Switzerland | 3010 |
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
Study Documents (Full-Text)
None provided.More Information
Publications
- Bassetti C, Aldrich MS. Idiopathic hypersomnia. A series of 42 patients. Brain. 1997 Aug;120 ( Pt 8):1423-35.
- 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.
- 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.
- 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.
- 2019-00788