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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Narcolepsy; Cataplexy; Idiopathic Hypersomnia
• Intervention / Treatment: Diagnostic test: Quantitative mass spectrometry assay

• Study Type: Interventional
• Enrollment (Anticipated): 117
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Orexin-A dosage by radioimmunoassay	Radioimmunoassay for orexin-A dosage in cerebrospinal fluid	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	the score will be between 0 and 24, higher scores mean a worse outcome	Day 1
Narcolepsy severity scale (NSS)	the score will be between 0 and 57, higher scores mean a worse outcome	Day 1
Hypersomnolence severity scale (IHSS)	the score will be between 0 and 50, higher scores mean a worse outcome	Day 1
Insomnia severity index	the score will be between 0 and 32, higher scores mean a worse outcome	Day 1
Iterative sleep latency tests (TILE)		Up to 24 hours
Presence of the HLA allele DQB1*06:02		Day 1

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Anticipated): January 30, 2023
• Primary Completion (Anticipated): July 30, 2025
• Study Completion (Anticipated): October 30, 2025

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: November 7, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: sleepiness; orexin/hypocretin
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Narcolepsy; Cataplexy; Idiopathic Hypersomnia
• Other Study ID Numbers: RECHMPL22_0072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No