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

Narcolepsy Clinical Trial

— MRM-OREX  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05615584
• Other study ID #: RECHMPL22_0072
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 30, 2023
• Est. completion date: October 30, 2025

Study information

• Verified date: November 2022
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 117
• Est. completion date: October 30, 2025
• Est. primary completion date: July 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cataplexy
• Disorders of Excessive Somnolence
• Idiopathic Hypersomnia
• Narcolepsy

Intervention

Diagnostic Test:
• Quantitative mass spectrometry assay
ORX-A determination by quantitative mass spectrometry

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Orexin-A dosage by Multiple Reaction Monitoring Mass Spectrometry	Multiple Reaction Monitoring mass spectrometry for orexin-A dosage in cerebrospinal fluid	Day 1 (=day of inclusion)
Primary	Orexin-A dosage by radioimmunoassay	Radioimmunoassay for orexin-A dosage in cerebrospinal fluid	Day 1
Secondary	Age of onset of hypersomnia symptoms		Day 1
Secondary	Frequency of cataplexy		Up to 24 hours
Secondary	Characteristics of cataplexy		Up to 24 hours
Secondary	Average duration of cataplexy		Up to 24 hours
Secondary	Epworth sleepiness scale (ESS)	the score will be between 0 and 24, higher scores mean a worse outcome	Day 1
Secondary	Narcolepsy severity scale (NSS)	the score will be between 0 and 57, higher scores mean a worse outcome	Day 1
Secondary	Hypersomnolence severity scale (IHSS)	the score will be between 0 and 50, higher scores mean a worse outcome	Day 1
Secondary	Insomnia severity index	the score will be between 0 and 32, higher scores mean a worse outcome	Day 1
Secondary	Iterative sleep latency tests (TILE)		Up to 24 hours
Secondary	Presence of the HLA allele DQB1*06:02		Day 1