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

NCT06292598 | Recruiting

• 1 other identifier: AOI2022/2023/CDR-01
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Narcolepsy Type 1; Bacterial Translocation

Outcome Measures

Primary Outcomes (1)

• Plasma bacterial translocation profiles between groups

  Circulating plasma r16s DNA (copies/μL)

  Day 0

Secondary Outcomes (24)

• Plasma bacterial translocation profiles in NT1 patients

  Month 12

• Taxonomic characteristics of DNA in the CSF of NT1 patients according to narcolepsy severity

  Day 0

• Taxonomic characteristics of plasma bacterial DNA in patients with high bacterial translocation

  Day 0

• Taxonomic characteristics of plasma bacterial DNA in patients with high bacterial translocation

  Month 12

• Beta diversity of the intestinal microbiota between groups

  Day 0

Study Arms (2)

Patients with untreated NT1

Other: Blood sample; Other: Stool sample; Other: CSF sample

Matched controls

Controls matched on sex, age (+/- 2 years) and BMI class (BMI \< 25: normal; 25 ≤ BMI ≤ 30: overweight; BMI \> 30: obesity)

Other: Blood sample; Other: Stool sample

Interventions

Blood sample OTHER

Sample taken to test plasma permeability markers

Matched controls; Patients with untreated NT1

Stool sample OTHER

Sample taken to test microbial diversity and composition

Matched controls; Patients with untreated NT1

CSF sample OTHER

Sample taken to test orexin level

Patients with untreated NT1

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults or children (≥10 years) with type 1 narcolepsy managed at the Montpellier and Nîmes teaching hospitals. This population will be matched on sex, age (± 2 years) and BMI class (BMI \< 25: normal; 25 ≤ BMI ≤ 30: overweight; BMI \> 30: obese) with a population of control subjects without central hypersomnolence, consulting the participating services mainly for another sleep disorder.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (2)

Nîmes University Hospital

Nîmes, Gard, 30029, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Montpellier

Montpellier, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood and fecal samples

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Catherine Dunyach-Remy

  CHU de Nimes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Catherine Dunyach-Remy

CONTACT

0466683202; catherine.remy@chu-nimes.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 5, 2024
• Study Start: March 10, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: November 17, 2025

Record last verified: 2025-11

Locations

FR (2)