Identifying Biomarkers in ALS Patients Using Neuronal Derived Extracellular Vesicles

NCT ID: NCT07334743

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-09-17
• Study Completion Date: 2029-09-30

Brief Summary

Rationale. ENGRAILED1 (EN1) is under consideration as a therapeutic approach for amyotrophic lateral sclerosis (ALS). To assess EN1 target engagement in patients, we aim to identify EN1-responsive biomarkers suitable as Prentice-style surrogate endpoints. We will discover candidates by RNA-seq of neuron-derived extracellular vesicles (NVEC) immuno-isolated from blood. Establishing such biomarkers would enable and de-risk early-phase (I/II) EN1 trials.

Primary endpoint. Discovery: RNA-seq identification of circulating NVEC-borne biomarkers that differ between sporadic ALS patients and healthy controls.

EN1 modulation: Demonstration that these biomarkers are modulated by EN1 in En1+/- mouse models and in ALS patient iPSC-derived motor neurons.

Design. Prospective cohort, N=60 (30 sporadic ALS; 30 healthy controls matched on age/sex).

Population. Adults undergoing diagnostic work-up for suspected sporadic ALS; healthy volunteers without neurological disease.

Key procedures and timeline. Baseline (M0, inpatient): ALSFRS-R, MRC, hand dynamometry, eye-movement recording (MOC); NCS/EMG (NUMIX), TMS/MEP with cortical excitability; neuropsychology; brain & spinal MRI; pulmonary function testing; CSF (10 mL) and blood (15 mL) for clinical labs and research (NVEC immunocapture → RNA-seq; proteomics).

Follow-up: M6 clinic visit (repeat clinical/electrophysiology/neuropsychology/PFTs as per care) with blood (15 mL); additional routine follow-ups at M12, M18, M24 (clinical; MOC at M12 and M24).

Controls: single visit with blood (3×5 mL EDTA) and cortical excitability; brain MRI for targeting.

Sample size. 60 participants total (30 ALS, 30 controls).

Conditions

Amyotrophic Lateral Sclerosis; ENGRAILED1

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

patients with ALS

No interventions assigned to this group

controls without ALS

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

For patients :

Age ≥ 18 years. Diagnostic suspicion of amyotrophic lateral sclerosis (ALS). Planned inpatient admission in the HFAR neurology department for the standard diagnostic work-up as part of routine care: clinical evaluation, neuropsychological assessment, nerve conduction studies/EMG, motor evoked potentials (TMS/MEP), brain and spinal MRI, pulmonary function testing, lumbar puncture, and standard blood tests.

Explicit written informed consent to participate in the study. Affiliation with or beneficiary of a social security system.

Patient under legal protection/guardianship. Pregnant or breastfeeding woman. Active infection within the 4 weeks preceding biological sampling. Ongoing diagnosis and management of cancer.

Secondary exclusion criterion:

ALS diagnosis not confirmed.

For Healthy Controls :

Age ≥ 18 years. Explicit written informed consent to participate in the study. Affiliation with or beneficiary of a social security system.

Exclusion Criteria

• Patient under legal protection/guardianship.
• Pregnant or breastfeeding woman.
• Diagnosed neurological disease.
• Self-reported cognitive impairment.
• Active infection within the 4 weeks prior to biological sampling.
• Current diagnosis and management of cancer.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Fondation Ophtalmologique Adolphe de Rothschild

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hopital Fondation Adolphe de Rothschild

Paris, , France

Site Status: RECRUITING

Countries

France

Facility Contacts

Antoine Gueguen, MD

Role: primary

neurologie@for.paris

01 48 03 65 65

Other Identifiers

AGN_2024_9

Identifier Type: -

Identifier Source: org_study_id