Maladies Neurologiques Auto-immunes et Secondaires à l'immunothérapie : étude Des mécanismes Immunologiques et Recherche Des Cibles de l'Attaque Immune
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 4
- 主要终点
- Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Study group : cancer patients developing neurological symptoms after starting treatment with immune
干预措施: Lumbar puncture and blood sampling (Other)
Control group : cancer patients undergoing treatment with ICIs and experiencing neurological symptom
干预措施: Lumbar puncture and blood sampling (Other)
Control group : patients with an autoimmune disease of the central nervous system
干预措施: Lumbar puncture and blood sampling (Other)
Control group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperte
干预措施: Lumbar puncture and blood sampling (Other)
结局指标
主要结局
Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity
时间窗: At day 1
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.
次要结局
- 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)