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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Encephalitis Autoimmune; Acute Disseminated Encephalomyelitis
• Intervention / Treatment: Other: Blood test

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nail BENALLEGUE, DOCTOR; Phone Number: +33241354445; Email: nail.benallegue@chu-angers.fr

Study Locations

• France
  • Angers, France, 49240
    • Recruiting
    • CHU d'Angers
    • Contact: Nail Benallegue, Doctor; Phone Number: +332 41 35 44 45; Email: nail.benallegue@chu-angers.fr
  • Brest, France, 29200
    • Recruiting
    • Univesity Hostipal of Brest
    • Contact: Juliette Ropars, MD; Phone Number: 33-(0)2-98-22-33-89; Email: juliette.ropars@chu-brest.fr
  • Le Kremlin-Bicêtre, France, 94270
    • Recruiting
    • Univesity Hostipal of APHP
    • Contact: Deiva Kumaran, MD; Phone Number: 33-(0)1-45-21-31-12; Email: kumaran.deiva@aphp.fr
  • Montpellier, France, 34295
    • Not yet recruiting
    • CHU Montpellier
    • Contact: Pierre MEYER, DR; Phone Number: +334 67 33 74 22; Email: p-meyer@chu-montpellier.fr
  • Nantes, France, 44093
    • Recruiting
    • Univesity Hostipal of Nantes
    • Contact: Capucine GLASSON, MD; Phone Number: 33-(0)2-40-16-51-76; Email: capucine.lefebvre@chu-nantes.fr
  • Paris, France, 75015
    • Not yet recruiting
    • Hôpital Necker Enfants Malades
    • Contact: Mélodie AUBART, DR; Phone Number: +331 42 19 26 93; Email: melodie.aubart@aphp.fr
  • Rennes, France, 35000
    • Recruiting
    • Univesity Hostipal of Rennes
    • Contact: Silvia Napuri-Peirano, MD; Phone Number: 33-(0)2-99-26-71-14; Email: Silviaadriana.napuri.peirano@chu-rennes.fr
  • Tours, France, 37000
    • Recruiting
    • Univesity Hostipal of Tours
    • Contact: Pierre Castelnau, MD; Phone Number: 33-(0)2-47-47-47-47; Email: castelnau@univ-tours.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

Prospective recruitment Pre-inclusion criteria

• Age at inclusion between 1 and 18 years (included)
• First demyelinating event at inclusion, such as ADEM encephalitis, optic neuritis (NORB) or myelitis, or a combination of these conditions.
• Informed consent signed by patient's legal representative
• Patient affiliated to or benefiting from a social security scheme Inclusion criteria (confirmation of inclusion and follow-up in one of 3 groups)
• 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.

Retrospective recruitment General inclusion criteria

• Age at inclusion between 1 and 18 years (inclusive)
• Inclusion (signed consent of the patient's legal representative) in the biocollection from which the samples were taken at the latest at the time of management of a first demyelinating event of the ADEM encephalitis, optic neuritis (NORB) or myelitis type, or a combination of these disorders.
• PBMC collected at the time of the first demyelinating event before any immunomodulatory treatment, cryopreserved and available in the biocollection.
• Depending on the date of inclusion (if inclusion beyond 6 to 24 months after the first demyelinating event), samples taken at 6 months and then 24 months after the first demyelinating event available in the biocollection for the analyses planned in the study.
• Informed consent signed by patient's legal representative
• Patient affiliated to or benefiting from a social security scheme

Inclusion criteria specific to the 3 study groups

• 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.

Non-inclusion criteria (prospective or retrospective recruitment):

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADEM non-MOGAD; Non-MOGAD ADEM control group of 5 patients with anti-MOG antibody-negative ADEM	Other: Blood test; Drawing blood to realize biomarkers of disease course of MOGAD-ADEM and pathophysiology of ADEM (and MOGAD) : cellular and molecular signatures, inflammatory signaling.
Active Comparator: ADEM MOGAD; Single-phase and multi-phase ADEM MOGAD units respectively	Other: Blood test; Drawing blood to realize biomarkers of disease course of MOGAD-ADEM and pathophysiology of ADEM (and MOGAD) : cellular and molecular signatures, inflammatory signaling.
Experimental: MOGAD non-ADEM; MOGAD non-ADEM central nervous system demyelinating neuroinflammatory control group (anti-MOG antibody-positive optic neuritis or myelitis) of 5 patients	Other: Blood test; Drawing blood to realize biomarkers of disease course of MOGAD-ADEM and pathophysiology of ADEM (and MOGAD) : cellular and molecular signatures, inflammatory signaling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Investigators: Principal Investigator: Nail BENALLEGUE, DOCTOR, University Hospital, Angers

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: March 4, 2025
• First Posted (Actual): March 7, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Post-Infectious Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Demyelinating Diseases; Leukoencephalopathies; Pathological Conditions, Signs and Symptoms; Autoimmune Diseases of the Nervous System; Encephalomyelitis, Acute Disseminated; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests
• Other Study ID Numbers: 2024-A02732-45

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared upon reasonable request. Only de-identified data will be shared. Any data collected during the study may be shared. The protocol will be shared initially. Other documents may be shared at a later date upon request (e.g., the CRF to allow a collaborator to select the data they wish to access). The recipients of the data will be researchers. The data will be available for any purpose deemed relevant by the study investigator, based on a protocol provided by the requester, after verification of the obtaining of regulatory approvals, including the favorable opinion of an ethics committee.
• IPD Sharing Time Frame: The data will be shared after signing a negotiated data transfer agreement ( data access agreement), for the duration specified in the agreement.
• IPD Sharing Access Criteria: The data will be made available via secure transfer (sharing platform approved by the university hospital: BlueFiles or Oodrive).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No