Bacterial Translocation and Gut Microbiota in Type 1 Narcolepsy Patients Versus a Control Population

Narcolepsy Type 1 Clinical Trial

— NARCOBIOTE  

Official title:

Bacterial Translocation and Gut Microbiota in Type 1 Narcolepsy Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06292598
• Other study ID #: AOI2022/2023/CDR-01
• Status: Not yet recruiting
• Start date: May 2024
• Est. completion date: May 2027

Study information

• Verified date: February 2024
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: Catherine Dunyach-Remy
• Phone: 0466683202
• Email: catherine.remy[@]chu-nimes.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years and older

Eligibility

Inclusion Criteria:

• Patient diagnosed with narcolepsy type 1 (NT1).

• Patient not treated for narcolepsy during initial evaluation of NT1 patients.

• Patient eligible for treatment for longitudinal monitoring of NT1 patients.

• Patient speaking and understanding French.

• The patient must have given their free and informed consent and signed the consent form or consent has been provided from the holder(s) of parental authority or the legal guardian and the child.

• The patient must be a member or beneficiary of a health insurance plan

Inclusion criteria for control subjects:

• Absence of diagnosis of sleep disorder responsible for hypersomnolence with an Epworth sleepiness scale score greater than 10/24.

Exclusion Criteria:

• Subject having presented an infectious pathology requiring antibiotic treatment in the previous 3 months.

• Subject with a dysimmune pathology.

• Subject having had treatment with an immunomodulatory molecule or chemotherapy within 60 days before inclusion in the research or whose indication is planned for the duration of the research.

• Subject with a chronic digestive pathology or having undergone bariatric surgery in the previous year.

• Subject on laxative.

• Subject living in a medical institution.

• Subject under legal protection, guardianship or curatorship.

• Subject and/or their legal representative (if a minor patient) unable to express consent

• Taking antibiotics during the inclusion period, or laxative or any other treatment having a significant impact on the microbiota

Related Conditions & MeSH terms

• Bacterial Translocation
• Narcolepsy
• Narcolepsy Type 1

Intervention

Other:
• Blood sample
Sample taken to test plasma permeability markers
• Stool sample
Sample taken to test microbial diversity and composition
• CSF sample
Sample taken to test orexin level

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Montpellier	Montpellier
France	Nîmes University Hospital	Nîmes	Gard

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma bacterial translocation profiles between groups	Circulating plasma r16s DNA (copies/µL)	Day 0
Secondary	Plasma bacterial translocation profiles in NT1 patients	Circulating plasma r16s DNA (copies/µL)	Month 12
Secondary	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)	Day 0
Secondary	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 (%)	Day 0
Secondary	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 (%)	Month 12
Secondary	Beta diversity of the intestinal microbiota between groups	measured by metabarcoding	Day 0
Secondary	Beta diversity of the intestinal microbiota in NT1 patients	measured by metabarcoding	Month 12
Secondary	Alpha diversity of the intestinal microbiota between groups	measured by metabarcoding	Day 0
Secondary	Alpha diversity of the intestinal microbiota in NT1 patients	measured by metabarcoding	Month 12
Secondary	Composition of the intestinal microbiota between groups	Relative abundance of bacterial phyla and genera (%) measured by metabarcoding	Day 0
Secondary	Composition of the intestinal microbiota between groups	Relative abundance of bacterial phyla and genera (%) measured by metabarcoding	Month 12
Secondary	Plasma Intestinal Fatty Acid Binding Protein (i-FABP) profile between groups	Measured by ELISA (pg/mL)	Day 0
Secondary	Plasma Intestinal Fatty Acid Binding Protein (i-FABP) profile in NT1 patients	Measured by ELISA (pg/mL)	Month 12
Secondary	Plasma LPS-binding Protein (LBP) profile between groups	Measured by ELISA (µg/mL	Day 0
Secondary	Plasma LPS-binding Protein (LBP) profile in NT1 patients	Measured by ELISA (µg/mL	Month 12
Secondary	Plasma Soluble CD14 profile between groups	Measured by ELISA (µg/mL	Day 0
Secondary	Plasma Soluble CD14 profile in NT1 patients	Measured by ELISA (µg/mL	Month 12
Secondary	Age of onset of symptoms in NT1 patients	Years	Day 0
Secondary	Duration of disease progression in NT1 patients	Years	Day 0
Secondary	Severity of sleep-related symptoms in NT1 patients	Epworth scale	Day 0
Secondary	Severity of narcolepsy symptoms in NT1 patients	Narcolepsy Severity Scale	Day 0
Secondary	Description of comorbidities in NT1 patients	List	Day 0
Secondary	Sleep onset latency in NT1 patients	Minutes	Day 0
Secondary	Number of rapid eye movement sleep episodes in NT1 patients	Number	Day 0
Secondary	Orexin levels in CSF in NT1 patients	Measured by Radio-immuno-assay (pg/ml)	Day 0