Autoimmune Neurological Diseases and Those Secondary to Immunotherapy: Study of Immunological Mechanisms and Research Into Targets of Immune Attack
DINAMIC
Maladies Neurologiques Auto-immunes et Secondaires à l'immunothérapie : étude Des mécanismes Immunologiques et Recherche Des Cibles de l'Attaque Immune
1 other identifier
interventional
160
1 country
4
Brief Summary
The pathophysiology of neurological toxicities secondary to immune checkpoint inhibitors (ICIs) is unknown. Various mechanisms have been proposed: activation of cytotoxic CD8 T cells, autoantibodies via activation of B cells and CD4 cells, non-specific inflammation through the production of pro-inflammatory cytokines, and complement activation. The aim of this research is to characterise the pathophysiological mechanisms of neurotoxicities in cancer patients treated with ICIs.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Apr 2026
Longer than P75 for not_applicable
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 11, 2026
CompletedFirst Posted
Study publicly available on registry
March 6, 2026
CompletedStudy Start
First participant enrolled
April 9, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 9, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 9, 2030
July 7, 2026
March 1, 2026
4.7 years
February 11, 2026
July 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity
Specific TCR repertoires of ICI-related neurotoxicity will be identified by TCR sequencing of CSF and blood lymphocytes of patients at the time of diagnosis of neurotoxicity of ICIs in comparison to those found in the control cohort 1.2. The target of these lymphocytes specifically found in cohort 1.1 will be assessed by EliSpot with known neuronal antigens as well as a search for serum and CSF onconeuronal autoantibodies. In silico methods as well as public TCR database will also be used to find the neurological targets.
At day 1
Secondary Outcomes (3)
Proportions of lymphocytes
At day 1
Concentration of pro and anti-inflammatory cytokines in CSF of patients with ICI-related neurotoxicity and control cohorts
At day 1
Presence and strength of correlation between TCR repertoires and phenotype/ expression profile of CSF lymphocytes and clinical presentation of ICI-related neurotoxicity
At day 1
Study Arms (4)
Study group : cancer patients developing neurological symptoms after starting treatment with immune
EXPERIMENTALControl group : cancer patients undergoing treatment with ICIs and experiencing neurological symptom
EXPERIMENTALControl group : patients with an autoimmune disease of the central nervous system
EXPERIMENTALControl group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperte
EXPERIMENTALInterventions
For all patients in the study, lumbar puncture will be performed as part of their care, according to the clinical indication given by the referring physician. If the patient gives their consent, an additional volume of CSF will be collected for this study, so that the total volume collected (care plus research) does not exceed 5 mL. No lumbar puncture will be performed specifically for the study. Blood samples will also be collected: these are additional blood tubes collected during a blood sample taken as part of the treatment (as described in the section 'Minimal risks and constraints added by the research').
Eligibility Criteria
You may qualify if:
- Adult patient (aged ≥ 18 years)
- Affiliated with a social security scheme
- Express consent to participate in the study
- Indication for lumbar puncture And
- Patients with cancer, undergoing treatment with ICIs, presenting neurological symptoms after starting treatment with ICIs. These symptoms must have appeared no more than 3 months after the last administration of ICIs.
- Patients with an autoimmune disease of the central nervous system (diagnosis made by teams 1, 2 and 3) according to internationally recognised criteria, with no history of active cancer in the last 3 years and no other autoimmune disease Or
- Patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hypertension (diagnosed based on imaging (brain MRI) and clinical findings), with no history of active cancer in the last 3 years and no active autoimmune disease
You may not qualify if:
- Contraindication or refusal to perform a lumbar puncture
- Sample not suitable for research (volume of CSF collected for treatment \>5 mL)
- Pregnant or breastfeeding women
- Not affiliated with the social security system, patients under French State Medical Aid for undocumented migrants
- Patients under guardianship or curatorship, under judicial protection measures, or deprived of their liberty by judicial or administrative decision
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
Hôpital Bicêtre AP-HP
Le Kremlin-Bicêtre, France
Fondation Rotschild
Paris, France
Hôpital Saint Louis AP-HP
Paris, France
Hôpital Saint Louis
Paris, France
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 11, 2026
First Posted
March 6, 2026
Study Start
April 9, 2026
Primary Completion (Estimated)
December 9, 2030
Study Completion (Estimated)
December 9, 2030
Last Updated
July 7, 2026
Record last verified: 2026-03