Neurological DiseasesDINAMICNCT07456358
Autoimmune Neurological Diseases and Those Secondary to Immunotherapy: Study of Immunological Mechanisms and Research Into Targets of Immune Attack
A study testing Lumbar puncture and blood sampling in people with Neurological Diseases and Auto Immune Disease, run by Assistance Publique - Hôpitaux de Paris at 4 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Neurological Diseases, Auto Immune Disease
- What is being tested?
- Lumbar puncture and blood sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 4 sitesFrance
- Study dates
- 9 Apr 2026to 9 Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France4 sites, 4 recruiting
- Recruiting
Hôpital Bicêtre AP-HP
Le Kremlin-Bicêtre
Cécile Cauquil, MD, 01 45 21 25 02 ext. +33, cecile.cauquil@aphp.fr
- Not yet recruiting
Fondation Rotschild
Paris
Caroline Papeix, MD PhD, 0148036852 ext. +33, cpapeix@for.paris
- Recruiting
Hôpital Saint Louis AP-HP
Paris
Stefania Cuzzubbo, MD, 01 71 20 74 67 ext. +33, stefania.cuzzubbo@aphp.fr
- Recruiting
Hôpital Saint Louis
Paris
Céleste Lebbé, MD PhD, 01 42 49 99 61 ext. +33, celeste.lebbe@aphp.fr
About this study
Official title: Maladies Neurologiques Auto-immunes et Secondaires à l'immunothérapie : étude Des mécanismes Immunologiques et Recherche Des Cibles de l'Attaque Immune
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.
- Conditions
- Neurological Diseases, Auto Immune Disease
- Being tested
- Lumbar puncture and blood sampling
- Keywords
- Autoimmune neurological diseases, Immunotherapy, Neurotoxocities, Immune checkpoint inhibitors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lumbar puncture and blood samplingOther
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').
| Study group | Role | What they receive |
|---|---|---|
| Study group : cancer patients developing neurological symptoms after starting treatment with immune | Experimental | Not described Receives: Other: Lumbar puncture and blood sampling |
| Control group : cancer patients undergoing treatment with ICIs and experiencing neurological symptom | Experimental | Not described Receives: Other: Lumbar puncture and blood sampling |
| Control group : patients with an autoimmune disease of the central nervous system | Experimental | Not described Receives: Other: Lumbar puncture and blood sampling |
| Control group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperte | Experimental | Not described Receives: Other: Lumbar puncture and blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At day 1
Secondary outcomes (3)
Proportions of lymphocytes
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.
Measured: At day 1
Concentration of pro and anti-inflammatory cytokines in CSF of patients with ICI-related neurotoxicity and control cohorts
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.
Measured: 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
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.
Measured: At day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2026
- Study start9 Apr 2026
- Primary completion9 Dec 2030 (estimated)
- Study completion9 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurological DiseasesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07456358
- Sponsor's protocol ID
- APHP251304
- Acronym
- DINAMIC
- Status last verified
- Mar 2026
- First submitted
- 11 Feb 2026
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maladies Neurologiques Auto-immunes et Secondaires à l'immunothérapie : étude Des mécanismes Immunologiques et Recherche Des Cibles de l'Attaque Immune
- ClinicalTrials.gov ID
- NCT07456358
- Acronym / sponsor ID
- DINAMIC / APHP251304
- Conditions
- Neurological Diseases, Auto Immune Disease
- Keywords
- Autoimmune neurological diseases, Immunotherapy, Neurotoxocities, Immune checkpoint inhibitors
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 9 Apr 2026 (actual)
- Primary completion
- 9 Dec 2030 (estimated)
- Study completion
- 9 Dec 2030 (estimated)
- First posted
- 6 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Study group : cancer patients developing neurological symptoms after starting treatment with immune | Experimental | Other: Lumbar puncture and blood sampling |
| Control group : cancer patients undergoing treatment with ICIs and experiencing neurological symptom | Experimental | Other: Lumbar puncture and blood sampling |
| Control group : patients with an autoimmune disease of the central nervous system | Experimental | Other: Lumbar puncture and blood sampling |
| Control group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperte | Experimental | Other: Lumbar puncture and blood sampling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lumbar puncture and blood samplingFor 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'). | Other | 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 |
Primary outcome
Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity
Time frame: 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.
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lumbar puncture and blood sampling in people with Neurological Diseases and Auto Immune Disease, run by Assistance Publique - Hôpitaux de Paris at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stefania Cuzzubbo, MD (0171207467 ext. +33, stefania.cuzzubbo@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity (time frame: At day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.