Autoimmune Neurological Diseases and Those Secondary to Immunotherapy: Study of Immunological Mechanisms and Research Into Targets of Immune Attack

Official title

Maladies Neurologiques Auto-immunes et Secondaires à l'immunothérapie : étude Des mécanismes Immunologiques et Recherche Des Cibles de l'Attaque Immune

Overview

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.

Interventions

• Other Lumbar puncture and blood sampling
  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 sam

Primary outcome measures

• Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity [Time frame: At day 1]

Secondary outcome measures (3)

• Proportions of lymphocytes [Time frame: At day 1]
• Concentration of pro and anti-inflammatory cytokines in CSF of patients with ICI-related neurotoxicity and control cohorts [Time frame: 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 [Time frame: At day 1]

Eligibility criteria

Inclusion criteria

• 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.

Or

• 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

Exclusion criteria

• Contraindication or refusal to perform a lumbar puncture
• Sample not suitable for research (volume of CSF collected for treatment >5 mL)
• Corticosteroid therapy or other immunomodulatory treatment in progress (discontinued less than 15 days prior to inclusion)
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 4 centers

• Hôpital Bicêtre AP-HP — Le Kremlin-Bicêtre
• Fondation Rotschild — Paris
• Hôpital Saint Louis AP-HP — Paris
• Hôpital Saint Louis — Paris

Identifiers

NCT: NCT07456358 · APHP251304

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗