Narcolepsy type 1 (NT1) is a rare disease characterized by severe drowsiness, cataplexy, hypnagogic hallucinations, sleep paralysis, poor night sleep, and often obesity. NT1 is caused by irreversible loss of orexin (ORX)/hypocretin neurons in the lateral hypothalamus with decreased ORX levels in the cerebrospinal fluid (CSF). Although the underlying process leading to this destruction remains unclear; an autoimmune origin is suspected. The study authors recently compared the bacterial communities of the fecal microbiota of NT1 patients and control subjects. Initial results demonstrated a difference in overall bacterial community structure in NT1 compared to controls, as assessed by beta diversity, even after adjusting for body mass index (BMI). The Shannon biodiversity index was also correlated with the duration of NT1 disease. However, no association was found between the structure of the microbial community and the clinical characteristics of NT1 patients. In 2022, a second study from the SOMNOBANK cohort on a larger population confirmed these results, showing dysbiosis between NT1 patients and the control population. The altered intestinal microbial diversity supports the important role of the environment in the development and pathogenesis of NT1. Other studies have established a link between dysbiosis, intestinal permeability and inflammation in other neuroimmune pathologies. Currently, no study has focused on these phenomena of bacterial translocation, intestinal permeability and immune activation linked to the microbiota in type 1 narcolepsy patients. The study hypothesis is that NT1 patients with dysbiosis in their intestinal microbiota also present a bacterial translocation with an intestinal origin, leading to a systemic inflammatory syndrome favoring an autoimmune damage destroying hypocretin neurons in the hypothalamus. The study authors suspect that microbial elements (DNA) involved in the autoimmune process could be detected in the CSF. This bacterial translocation could vary over time depending on: i) the progression of the disease and its management; ii) changing dysbiosis and: iii) the increase in intestinal permeability and inflammation.
Study Type
OBSERVATIONAL
Enrollment
120
Sample taken to test plasma permeability markers
Sample taken to test microbial diversity and composition
Sample taken to test orexin level
Nîmes University Hospital
Nîmes, Gard, France
NOT_YET_RECRUITINGCentre Hospitalier Universitaire de Montpellier
Montpellier, France
RECRUITINGPlasma bacterial translocation profiles between groups
Circulating plasma r16s DNA (copies/μL)
Time frame: Day 0
Plasma bacterial translocation profiles in NT1 patients
Circulating plasma r16s DNA (copies/μL)
Time frame: Month 12
Taxonomic characteristics of DNA in the CSF of NT1 patients according to narcolepsy severity
Metagenomic sequencing of all genomes present, compared with international databases, presented as number of reads per species (bacterial, fungal and viral)
Time frame: Day 0
Taxonomic characteristics of plasma bacterial DNA in patients with high bacterial translocation
Metabarcoding of 16srDNA of bacterial DNA present in plasma in NT1 patients with 16S rDNA \>25 copies/μL, presented as relative abundance of bacterial phyla and genera (%)
Time frame: Day 0
Taxonomic characteristics of plasma bacterial DNA in patients with high bacterial translocation
Metabarcoding of 16srDNA of bacterial DNA present in plasma in NT1 patients with 16S rDNA \>25 copies/μL, presented as relative abundance of bacterial phyla and genera (%)
Time frame: Month 12
Beta diversity of the intestinal microbiota between groups
measured by metabarcoding
Time frame: Day 0
Beta diversity of the intestinal microbiota in NT1 patients
measured by metabarcoding
Time frame: Month 12
Alpha diversity of the intestinal microbiota between groups
measured by metabarcoding
Time frame: Day 0
Alpha diversity of the intestinal microbiota in NT1 patients
measured by metabarcoding
Time frame: Month 12
Composition of the intestinal microbiota between groups
Relative abundance of bacterial phyla and genera (%) measured by metabarcoding
Time frame: Day 0
Composition of the intestinal microbiota between groups
Relative abundance of bacterial phyla and genera (%) measured by metabarcoding
Time frame: Month 12
Plasma Intestinal Fatty Acid Binding Protein (i-FABP) profile between groups
Measured by ELISA (pg/mL)
Time frame: Day 0
Plasma Intestinal Fatty Acid Binding Protein (i-FABP) profile in NT1 patients
Measured by ELISA (pg/mL)
Time frame: Month 12
Plasma LPS-binding Protein (LBP) profile between groups
Measured by ELISA (μg/mL
Time frame: Day 0
Plasma LPS-binding Protein (LBP) profile in NT1 patients
Measured by ELISA (μg/mL
Time frame: Month 12
Plasma Soluble CD14 profile between groups
Measured by ELISA (μg/mL
Time frame: Day 0
Plasma Soluble CD14 profile in NT1 patients
Measured by ELISA (μg/mL
Time frame: Month 12
Age of onset of symptoms in NT1 patients
Years
Time frame: Day 0
Duration of disease progression in NT1 patients
Years
Time frame: Day 0
Severity of sleep-related symptoms in NT1 patients
Epworth scale
Time frame: Day 0
Severity of narcolepsy symptoms in NT1 patients
Narcolepsy Severity Scale
Time frame: Day 0
Description of comorbidities in NT1 patients
List
Time frame: Day 0
Sleep onset latency in NT1 patients
Minutes
Time frame: Day 0
Number of rapid eye movement sleep episodes in NT1 patients
Number
Time frame: Day 0
Orexin levels in CSF in NT1 patients
Measured by Radio-immuno-assay (pg/ml)
Time frame: Day 0
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