Clinical trial NCT05615584: Spectrometry (MRM) Versus I 125 Radioimmunoassay (RIA) for Quantification of Orexin-A of Patients With Hypersomnolence
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Narcolepsy
Idiopathic Hypersomnia
Cataplexy
Keywords: orexin/hypocretin
sleepiness
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2022-11-14
Enrollment: 117
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: 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

Primary outcomes:
measure: Orexin-A dosage by Multiple Reaction Monitoring Mass Spectrometry
timeFrame: Day 1 (=day of inclusion)
measure: Orexin-A dosage by radioimmunoassay
timeFrame: Day 1
Secondary outcomes:
measure: Age of onset of hypersomnia symptoms
timeFrame: Day 1
measure: Frequency of cataplexy
timeFrame: Up to 24 hours
measure: Characteristics of cataplexy
timeFrame: Up to 24 hours
measure: Average duration of cataplexy
timeFrame: Up to 24 hours
measure: Epworth sleepiness scale (ESS)
timeFrame: Day 1
measure: Narcolepsy severity scale (NSS)
timeFrame: Day 1
measure: Hypersomnolence severity scale (IHSS)
timeFrame: Day 1
measure: Insomnia severity index
timeFrame: Day 1
measure: Iterative sleep latency tests (TILE)
timeFrame: Up to 24 hours
measure: Presence of the HLA allele DQB1*06:02
timeFrame: Day 1
Other outcomes:
Locations:
city: Montpellier
country: France
facility: University Hospital of Montpellier
Study officials:
References: