International Swiss Primary Hypersomnolence and Narcolepsy Cohort Study

Recruiting

• Conditions: Idiopathic Hypersomnia; Hypersomnolence Disorder; Narcolepsy

• Registration Number: NCT04330963
• Lead Sponsor: Insel Gruppe AG, University Hospital Bern

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.

Study Timeline

• Study Start: 2020-01-06
• Study First Submitted: 2020-01-06
• Study First Submitted QC: 2020-03-31
• Study First Posted: 2020-04-02
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-17
• Last Update Posted: 2023-04-20
• Primary Completion: 2024-12-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Claudio L Bassetti; 🇨🇭 Bern, Switzerland