Viewing Study NCT03754348



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Last Modification Date: 2024-10-26 @ 12:58 PM
Study NCT ID: NCT03754348
Status: COMPLETED
Last Update Posted: 2024-05-29
First Post: 2018-11-05

Brief Title: Microglial Activation in Narcolepsy Type 1 and Kleine-Levin Syndrome Positron Emission Tomography PET Study in 18F DPA-714
Sponsor: University Hospital Montpellier
Organization: University Hospital Montpellier

Study Overview

Official Title: Microglial Activation in Narcolepsy Type 1 and Kleine-Levin Syndrome Positron Emission Tomography PET Study in 18F DPA-714
Status: COMPLETED
Status Verified Date: 2022-03
Last Known Status: Recruiting
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: NARCOGLIE
Brief Summary: Type 1 narcolepsy NT1 is a chronic sleep disorder caused by the selective and irreversible loss of neurons from the hypothalamus which synthesizes a neurotransmitter hypocretin Hcrt orexin The exact cause of this destruction is still unknown but the autoimmune hypothesis is strongly favored involving the interaction of genetic and environmental factors The treatment of NT1 is currently only symptomatic targeting hypersomnolence and cataplexy To prevent the destruction of Hcrt neurons immunomodulatory agents have been tested with varying efficacy probably due to varying degrees of hypothalamic impairment and stages of disease progression During microglial activation a condition associated with neuroinflammation in the brain there is an increase in the mitochondrial translocation protein TSPO which can be quantified in vivo by specific tracers such as the 18F DPA- 714 in positron emission tomography PET a very sensitive nuclear imaging technique The aim here is to study microglial activation in PET 18F DPA-714 in NT1 patients with recent evolution in comparison with controls then analyze the effect of age and the severity of symptoms on this PET imaging biomarker The hypothesis is that microglial activation especially of the hypothalamic region is greater in NT1 than controls
Detailed Description: Formerly known as narcolepsy with cataplexy narcolepsy type 1 NT1 is a rare and disabling sleep pathology that affects 002 of the population It occurs mainly in young adults and children with repercussions throughout their existence It is characterized by excessive daytime sleepiness EDS which is often the most disabling symptom Diurnal sleep access is irrepressible typically short-lived and refreshing Cataplexies are the most specific almost pathognomonic sign of this condition It is a loss of muscle tone in full consciousness sudden triggered by an often positive emotion laugh excitement joke Nighttime sleep is also disturbed and there may be other signs of paradoxical sleep dysregulation such as hypnagogic hallucinations at sleep or hypnopompic waking hallucinations and sleep paralysis

The diagnosis is confirmed by a polysomnographic recording PSG followed by iterative sleep latency tests TILE the next day According to the new international criteria ICSD-3 patients have a sleep latency of less than or equal to 8 minutes to TILE and at least 2 sleep in paradoxical sleep ESP An ESP during the previous night PSG can replace a TILE ESP Typical cataplexies must also be found during the interrogation but a level of hypocretin-1 collapsed in cerebrospinal fluid CSF 110 ng L can now be sufficient for diagnosis given its very high specificity 99 and sensitivity 87 for NT1

NT1 is due to the selective and irreversible loss of Hcrt neurons The exact cause of this destruction is still unknown but the autoimmune hypothesis is strongly favored The etiology is probably multifactorial involving genetic and environmental factors In fact 97 of patients with NT1 are carriers of the HLA Human Leukocyte Antigen allele DQB1 06 02 a class II major histocompatibility complex MHC allele

Treatments of NT1 are currently only symptomatic targeting the different symptoms drowsiness poor sleep at night cataplexy and other symptoms related to dysregulation of sleep Microglial activation is involved in the neuroinflammation process of certain central nervous system pathologies

When microglia are activated following aggression or cellular inflammation the expression of TSPO increases Positron Emission Tomography PET is a nuclear imaging technique that can be used to create anatomical and molecular images with high sensitivity New TSPO-specific tracers have been recently developed such as 18F DPA-714 to quantify in vivo microglial activation in brain PET

The goal here is to study the cerebral microglial activation in PET in NT1 patients with recent evolution appearance of the first symptoms - somnolence and cataplexy - less than 2 years ago in comparison with controls then analyze the effect of age and the severity of symptoms on this PET imaging biomarker Thus we hypothesize microglial activation particularly of the hypothalamic region in NT1 patients at an early stage of disease progression possibly correlated with the severity of symptoms To test this hypothesis we will compare the in vivo microglial activation with PET 18F DPA-714 in NT1 subjects versus control subjects followed for another age-and-sex-matched non-narcolepsy and hypersomnia-free sleep pathology The images will be analyzed semi-quantitatively by determining SuVr or normalized binding value a method validated in international studies

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None