High-throughput Omic Technology for Identification of Biomarkers of Relapsing Acute Disseminated Encephalomyelitis in Immune Cell Network

NCT06863974 | Recruiting

• 1 other identifier: 2024-A02732-45
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

Brief Summary

Acute disseminated encephalomyelitis (ADEM) is a neuroinflammatory disorder of the central nervous system, manifesting itself as impaired consciousness, even to the point of coma, and multifocal neurological deficits. ADEM is the most common encephalitis in children. Moreover, 50-65% of ADEM in children is associated with the presence of anti-MOG antibodies (MOGAD). In fact, ADEM is the most frequent clinical presentation of MOGAD in children, 50-75% before the age of 10. The risk of recurrence is higher in pediatric MOGAD of ADEM manifestation, up to 30%, compared to myelitis or optic neuritis. Multiphasic MOGAD are more frequently associated with sequelae in 50-69% of cases, versus 4-32% for monophasic forms. In ADEM, cognitive and epileptic sequelae predominate. The 2020 European consortium and the 2022 national diagnosis and care protocol recommend the introduction of disease-modifying therapies as early as the second attack of the disease, or in the event of distant sequelae, in order to limit relapses and sequelae. However, these treatments take several months to take effect. There is currently no reliable predictive factor for MOGAD recurrence other than the persistence of an elevated blood anti-MOG antibody level (≥1:1280) at 1 year. The aim of this study is therefore to identify biomarkers associated with MOGAD recurrence from the first attack. To this end, we will study the transcriptome of circulating blood mononuclear cells by single-cell next-generation RNA sequencing in children with anti-MOGAD neuroinflammatory relapses. Anticipating the multiphasic trajectory of the disease would enable the introduction of early disease-modifying therapy to prevent recurrences and long-term sequelae. Furthermore, the discovery of a molecular and/or cellular signature would provide a better understanding of the pathophysiology of ADEM and MOGAD.

Conditions

Encephalitis Autoimmune; Acute Disseminated Encephalomyelitis

Outcome Measures

Primary Outcomes (6)

• Blood sample

  1 tube (approx. 5 mL) for children under 12 kg, 2 tubes (approx. 10 mL) for children between 12 kg and 20 kg, 4 tubes (approx. 20 mL) for children over 20 kg. Collected tubes are transferred to the investigator's Biological Resource Center (BRC) for sample preparation of the biocollection, if accepted in the consent form, and preparation of circulating blood mononuclear cells (PBMC).

  Inclusion, 6 months, 24 months

• Age

  Inclusion

• Personal or family history of inflammatory or dysimmune disease

  Inclusion

• Weight

  Weight (kg)

  Inclusion, 6 months, 24 months

• EDSS (Expanded Disability Status Scale)

  The neurological examination is divided into eight functional systems, 4 major (pyramidal, cerebellar, sensory, brainstem), 4 minor (sphincter, vision, mental and other). A numerical score of increasing severity (0 to 6 or 7) is given to each functional system (FS). The overall scale score is measured on a 20-level scale (0 to 10 per half-point). Up to level 3.5, the score obtained in each FS (Functional System) and the number of FS reached automatically determine the EDSS score. From 4 to 7, the definition of each level is also given by the walking disability (ability to walk without stopping, need for assistance).

  Inclusion, 6 months, 24 months

• Neurological episodes consistent with demyelinating relapse since previous visit

  Number, date, neurological symptoms including chronic fatigue unusual for an individual of the same age, diagnosis of demyelinating relapse, type, hospitalization, treatment with intravenous corticosteroid bolus.

  6 months, 24 months

Study Arms (3)

ADEM non-MOGAD

EXPERIMENTAL

Non-MOGAD ADEM control group of 5 patients with anti-MOG antibody-negative ADEM

Other: Blood test

ADEM MOGAD

ACTIVE COMPARATOR

Single-phase and multi-phase ADEM MOGAD units respectively

Other: Blood test

MOGAD non-ADEM

EXPERIMENTAL

MOGAD non-ADEM central nervous system demyelinating neuroinflammatory control group (anti-MOG antibody-positive optic neuritis or myelitis) of 5 patients

Other: Blood test

Interventions

Blood test OTHER

Drawing blood to realize biomarkers of disease course of MOGAD-ADEM and pathophysiology of ADEM (and MOGAD) : cellular and molecular signatures, inflammatory signaling.

ADEM MOGAD; ADEM non-MOGAD; MOGAD non-ADEM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent signed by patient's legal representative
• MOGAD/ADEM group: presence of serum anti-MOG antibodies and diagnosis of ADEM (according to the International Pediatric Multiple Sclerosis Society Group (IPMSSG) criteria revised in 2013) at the first demyelinating attack.
• Non-MOGAD/ADEM group: anti-MOG antibodies negative and diagnosis of ADEM at first demyelinating attack.
• MOGAD/non-ADEM group: presence of serum anti-MOG antibodies and diagnosis of myelitis and/or NORB at first demyelinating attack.
• PBMC collected at the time of the first demyelinating event before any immunomodulatory treatment, cryopreserved and available in the biocollection.
• Informed consent signed by patient's legal representative
• Patient affiliated to or benefiting from a social security scheme
• MOGAD/ADEM group: presence of serum anti-MOG antibodies and diagnosis of ADEM (according to the International Pediatric Multiple Sclerosis Society Group (IPMSSG) criteria revised in 2013) at the first demyelinating attack.
• Non-MOGAD/ADEM group: anti-MOG antibodies negative and diagnosis of ADEM at first demyelinating attack.
• MOGAD/non-ADEM group: presence of serum anti-MOG antibodies and diagnosis of myelitis and/or NORB at first demyelinating attack.
• Immunosuppressive therapy in the 6 months prior to treatment for a first demyelinating event.
• Systemic corticosteroid therapy or immunomodulating doses of IV polyvalent immunoglobulin or plasma exchange within 3 months prior to treatment for a first demyelinating event.
• Brain MRI not performed at diagnosis of first demyelinating event
• Poor understanding of the French language

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (8)

CHU d'Angers

Angers, 49240, France

RECRUITING

Univesity Hostipal of Brest

Brest, 29200, France

RECRUITING

Univesity Hostipal of APHP

Le Kremlin-Bicêtre, 94270, France

RECRUITING

CHU Montpellier

Montpellier, 34295, France

NOT YET RECRUITING

Univesity Hostipal of Nantes

Nantes, 44093, France

RECRUITING

Hôpital Necker Enfants Malades

Paris, 75015, France

NOT YET RECRUITING

Univesity Hostipal of Rennes

Rennes, 35000, France

RECRUITING

Univesity Hostipal of Tours

Tours, 37000, France

RECRUITING

MeSH Terms

Conditions

Encephalomyelitis, Acute Disseminated; Autoimmune Diseases of the Nervous System

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Nervous System Diseases; Leukoencephalopathies; Brain Diseases; Central Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Nail BENALLEGUE, DOCTOR

  University Hospital, Angers

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nail BENALLEGUE, DOCTOR

CONTACT

+33241354445; nail.benallegue@chu-angers.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Prospective recruitment requires pre-inclusion because the characterization of antibodies allowing patients to be classified into these 3 groups is only done at a later stage.

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: March 7, 2025
• Study Start: November 16, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): February 1, 2030
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be shared after signing a negotiated data transfer agreement ( data access agreement), for the duration specified in the agreement.
• Access Criteria: The data will be made available via secure transfer (sharing platform approved by the university hospital: BlueFiles or Oodrive).

Locations

FR (8)