MRM-OREX: Spectrometry (MRM) Versus I 125 Radioimmunoassay (RIA) for Quantification of Orexin-A of Patients With Hypersomnolence

Sponsor

University Hospital, Montpellier (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05615584

Collaborator

(none)

117

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

In humans, selective loss of orexin neurons is responsible for type 1 narcolepsy (NT1), or narcolepsy with cataplexy, or orexin deficiency syndrome.

The International Classification of Sleep Disorders 3rd edition (ICSD-3) distinguishes between hypersomnolence of central origin: NT1, narcolepsy type 2 (NT2), or narcolepsy without cataplexy, and idiopathic hypersomnia (HI). These rare conditions are all characterised by hypersomnolence (excessive daytime sleepiness, or excessive need for sleep), which is the primary and often most disabling symptom. A level of ORX-A in cerebrospinal fluid (CSF) (<110 pg/mL) is a very sensitive and specific biomarker of NT1, currently sufficient for the diagnosis of this condition. In contrast, ORX neurons are thought to be intact in IH and NT2, and the pathophysiological mechanisms underlying these diseases remain unknown. Thus, their diagnosis is based solely on clinical and electrophysiological criteria.

The objective of this project is to determine the validity of a mass spectrometric technique for the determination of ORX-A in the cerebral spinal fluid of patients suffering from hypersomnolence in comparison with the radioimmunoassay which is the reference technique.

Condition or Disease	Intervention/Treatment	Phase
Narcolepsy Idiopathic Hypersomnia Cataplexy	Diagnostic Test: Quantitative mass spectrometry assay	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

117 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Multiple Reaction Monitoring (MRM) Versus I 125 Radioimmunoassay (RIA) for the Quantification of Orexin-A/Hypocretin-1 Levels in Cerebrospinal Fluid: a Prospective Diagnostic Validation Study in Patients With Hypersomnolence

Anticipated Study Start Date :

Jan 30, 2023

Anticipated Primary Completion Date :

Jul 30, 2025

Anticipated Study Completion Date :

Oct 30, 2025

Outcome Measures

Primary Outcome Measures

Orexin-A dosage by Multiple Reaction Monitoring Mass Spectrometry [Day 1 (=day of inclusion)]
Multiple Reaction Monitoring mass spectrometry for orexin-A dosage in cerebrospinal fluid
Orexin-A dosage by radioimmunoassay [Day 1]
Radioimmunoassay for orexin-A dosage in cerebrospinal fluid

Secondary Outcome Measures

Age of onset of hypersomnia symptoms [Day 1]
Frequency of cataplexy [Up to 24 hours]
Characteristics of cataplexy [Up to 24 hours]
Average duration of cataplexy [Up to 24 hours]
Epworth sleepiness scale (ESS) [Day 1]
the score will be between 0 and 24, higher scores mean a worse outcome
Narcolepsy severity scale (NSS) [Day 1]
the score will be between 0 and 57, higher scores mean a worse outcome
Hypersomnolence severity scale (IHSS) [Day 1]
the score will be between 0 and 50, higher scores mean a worse outcome
Insomnia severity index [Day 1]
the score will be between 0 and 32, higher scores mean a worse outcome
Iterative sleep latency tests (TILE) [Up to 24 hours]
Presence of the HLA allele DQB1*06:02 [Day 1]

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 8 years
Complaint of hypersomnolence and suspected central hypersomnolence
Benefiting from a standardised assessment: clinical, biological and neurophysiological
Lumbar puncture necessary for the assessment
Sufficient cerebrospinal fluid taken for biological analysis (at least 1 ml)
Signed informed consent

Exclusion Criteria:

Contraindication to lumbar puncture
Secondary hypersomnolence
Refusal to participate in the study or refusal of the lumbar puncture
Adult protected by law, or subject deprived of liberty, by judicial or administrative decision or patient under guardianship or curatorship
Subject not affiliated to the French social security system
Pregnant or breastfeeding woman