Ignite Creation Date:
2026-03-26 @ 3:18 PM
Ignite Modification Date:
2026-03-31 @ 1:30 AM
Study NCT ID:
NCT07456358
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-06
First Post:
2026-02-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Autoimmune Neurological Diseases and Those Secondary to Immunotherapy: Study of Immunological Mechanisms and Research Into Targets of Immune Attack
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'interventionBrowseModule': {'meshes': [{'id': 'D013129', 'term': 'Spinal Puncture'}, {'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D001706', 'term': 'Biopsy'}, {'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D003943', 'term': 'Diagnostic Techniques, Neurological'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 160}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-03-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-03', 'completionDateStruct': {'date': '2030-11-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-04', 'studyFirstSubmitDate': '2026-02-11', 'studyFirstSubmitQcDate': '2026-03-04', 'lastUpdatePostDateStruct': {'date': '2026-03-06', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2030-11-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity', 'timeFrame': 'At day 1', 'description': '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.\n\nThe 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.'}], 'secondaryOutcomes': [{'measure': 'Proportions of lymphocytes', 'timeFrame': 'At day 1', 'description': 'Absolute number and percentage of different cells subsets in CSF (CD3, CD20, CD4, CD8, C56) and of their phenotype (naif, effector memory, central memory, Treg) and expression profile will be assessed in study cohort and control cohorts by single cell RNA sequencing and flow cytometry.'}, {'measure': 'Concentration of pro and anti-inflammatory cytokines in CSF of patients with ICI-related neurotoxicity and control cohorts', 'timeFrame': 'At day 1', 'description': 'Measurement of CSF cytokines concentration by Single-Molecule Array and comparison of their levels in the four cohorts. The comparaison of cohort 1.1 with control cohort 3 will allow us to determine the normal level of each cytokine, the comparaison with the other cohorts will lead to the identification of the specific cytokine profile of ICI-related neurotoixicity.'}, {'measure': 'Presence and strength of correlation between TCR repertoires and phenotype/ expression profile of CSF lymphocytes and clinical presentation of ICI-related neurotoxicity', 'timeFrame': 'At day 1', 'description': 'Comparison of the proportions of TCR repertoire, phenotypic and expression profiles of the lymphocytes present in the CSF between the subgroups of patients with different neurological presentations (encephalitis, myelitis, meningitis, polyraduculonevritis, neuropathy) within the cohort 1.1 by using Spearman correlation.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Autoimmune neurological diseases', 'Immunotherapy', 'Neurotoxocities', 'Immune checkpoint inhibitors'], 'conditions': ['Neurological Diseases', 'Auto Immune Disease']}, 'descriptionModule': {'briefSummary': '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.\n\nThe aim of this research is to characterise the pathophysiological mechanisms of neurotoxicities in cancer patients treated with ICIs.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Adult patient (aged ≥ 18 years)\n* Affiliated with a social security scheme\n* Express consent to participate in the study\n* Indication for lumbar puncture And\n* 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.\n\nOr\n\n* 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\n* 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\n\nExclusion Criteria:\n\n* Contraindication or refusal to perform a lumbar puncture\n* Sample not suitable for research (volume of CSF collected for treatment \\>5 mL)\n* Corticosteroid therapy or other immunomodulatory treatment in progress (discontinued less than 15 days prior to inclusion)\n* Pregnant or breastfeeding women\n* Not affiliated with the social security system, patients under French State Medical Aid for undocumented migrants\n* Patients under guardianship or curatorship, under judicial protection measures, or deprived of their liberty by judicial or administrative decision'}, 'identificationModule': {'nctId': 'NCT07456358', 'acronym': 'DINAMIC', 'briefTitle': 'Autoimmune Neurological Diseases and Those Secondary to Immunotherapy: Study of Immunological Mechanisms and Research Into Targets of Immune Attack', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': "Maladies Neurologiques Auto-immunes et Secondaires à l'immunothérapie : étude Des mécanismes Immunologiques et Recherche Des Cibles de l'Attaque Immune", 'orgStudyIdInfo': {'id': 'APHP251304'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Study group : cancer patients developing neurological symptoms after starting treatment with immune', 'interventionNames': ['Other: Lumbar puncture and blood sampling']}, {'type': 'EXPERIMENTAL', 'label': 'Control group : cancer patients undergoing treatment with ICIs and experiencing neurological symptom', 'interventionNames': ['Other: Lumbar puncture and blood sampling']}, {'type': 'EXPERIMENTAL', 'label': 'Control group : patients with an autoimmune disease of the central nervous system', 'interventionNames': ['Other: Lumbar puncture and blood sampling']}, {'type': 'EXPERIMENTAL', 'label': 'Control group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperte', 'interventionNames': ['Other: Lumbar puncture and blood sampling']}], 'interventions': [{'name': 'Lumbar puncture and blood sampling', 'type': 'OTHER', 'description': "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.\n\nBlood 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').", 'armGroupLabels': ['Control group : cancer patients undergoing treatment with ICIs and experiencing neurological symptom', 'Control group : patients with an autoimmune disease of the central nervous system', 'Control group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperte', 'Study group : cancer patients developing neurological symptoms after starting treatment with immune']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Stefania Cuzzubbo, MD', 'role': 'CONTACT', 'email': 'stefania.cuzzubbo@aphp.fr', 'phone': '0171207467', 'phoneExt': '+33'}, {'name': 'Jérôme Lambert, MD PhD', 'role': 'CONTACT', 'email': 'jerome.lambert@u-paris.fr', 'phone': '0142499742', 'phoneExt': '+33'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}