Role of Neuroinflammation and Blood-Brain Barrier Breakdown in Intracerebral Hemorrhage.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

This interventional research has obtained funding from the French National Research Agency (ANR)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To evaluate the effect of perihematomal neuroimmune response, assessed by a quantitative measure of 18F-DPA-714 PET radiotracer uptake (binding within PHE) at day 10 ±2 after spontaneous ICH, on the functional outcome (poor versus favorable) at 6 months

Secondary objectives 6

1.  To evaluate the effect of perihematomal neuroimmune response, assessed by other PET-derived quantitative measures of 18F-DPA-714 radiotracer uptake at day 10 ±2 after spontaneous ICH, on the functional outcome (poor versus favorable) at 6 months
2.  To evaluate the effect of perihematomal neuroimmune response as assessed by PET-derived quantitative measures of 18F-DPA-714 uptake at day 10 ±2 after ICH on other clinical outcomes: o Early (within 14 days) neurological deterioration, o early (within 30 days) death, o functional outcome at 6 months o mortality at 6 months
3.  To evaluate at day 10 ±2 after ICH the correlations of perihematomal neuroimmune response as assessed with 18F-DPA-714 PET with other measures of neuroimmune response: o the blood brain barrier (BBB) breakdown as assessed with DCE-MRI; o the level of a panel of inflammatory (pro- and anti-) biomarkers
4.  To evaluate the effect of BBB breakdown and inflammatory plasma biomarkers at day 10 ±2 after ICH onset on the functional outcome (poor versus favorable) at 6 months;
5.  To compare the performance of 18F-DPA-714 PET, DCE-MRI and inflammatory plasma biomarkers at day 10 ±2 after ICH onset to predict the functional outcome (poor versus favorable) at 6 months.
6.  To identify baseline clinical and imaging variables associated with increased neuroimmune response (TSPO PET) and BBB breakdown (DCE-MRI) at day 10 ±2 after ICH

Conditions and MedDRA coding

Intracerebral hemorrhage.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1) Adults (≥ 18 years old);
2. 2) presenting with a symptomatic spontaneous supratentorial ICH;
3. 3) ICH within 48 hours after symptoms onset (or last seen well);
4. 4) ICH confirmed by brain imaging;
5. 5) Informed consent documented;
6. 6) Affiliated or beneficiary of social security scheme

Exclusion criteria 15

1. 1) Massive ICH volume (≥ 60 ml) at admission
2. 2) Severe coma (defined as a Glasgow Coma Scale score < 6) at admission;
3. 3) Planned neurosurgical hematoma evacuation;
4. 4) Decision already taken for palliative care with withdrawal of active treatment;
5. 5) Pre-existing dependence defined as a mRS score ≥2 prior to ICH occurrence;
6. 6) Underlying secondary cause of ICH including macrovascular causes (brain arteriovenous malformation, intracranial aneurysm, dural arteriovenous fistula, cavernous malformation), brain tumour, cerebral venous thrombosis, hemorrhagic infarction. Patients taking oral anticoagulant can be included;
7. 7) TSPO genotyping demonstrating a low affinity binder profile,
8. 8) Unable to tolerate or contraindicated to brain MRI: medical material not MRI compatible, claustrophobia, known hypersensitivity to gadoteric acid, meglumin or any drug containing gadolinium;
9. 9) Estimated glomerular filtration rate < 30 ml/min/1.73 m 2;
10. 10) Unable to tolerate or contraindicated to 18F-DPA714 PET: women who are pregnant or breastfeeding, claustrophobia, and known hypersensitivity to DPA-714;
11. 11) Use of Benzodiazepines within 7 days (within 6 weeks for prazepam, diazepam or clorazepate) preceding TSPO PET acquisition;
12. 12) Co-existing neuroinflammatory disease such as Multiple Sclerosis, Neuromyelitis optica, Neurosarcoidosis, autoimmune encephalitis, CNS vasculitis;
13. 13) Conditions requiring long-term immunosuppressive medication;
14. 14) Expected impossible follow-up or poor compliance;
15. 15) Patient under tutorship, curatorship, or legal protection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. o 18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR) within the perihematomal edema (PHE) using the mirror region of interest (ROI) in the contralateral hemisphere as reference
2. o The functional outcome at 6 months after ICH is quantified by the modified Rankin scale (which ranges from 0 [no symptoms] to 6 [death]). Poor functional outcome is defined as a modified Rankin scale score (mRs) ≥3

Secondary endpoints 11

1. o Volume of brain tissue within the perihematomal area with increased 18F-DPA-714 binding
2. o voxel-wise 18F-DPA-714 levels based on SuperVised Cluster Analysis (SVCA).
3. The associations of PET-derived quantitative measures of 18F-DPA-714 radiotracer uptake with: o Neurological deterioration within 14 days after ICH onset, defined as a ≥4‐point increase on the National Institutes of Health Stroke Scale (NIHSS) or ≥2‐point decrease on the Glasgow Coma Scale compared to baseline scores at the pre-inclusion visit;
4. o Early death defined as death at day 30
5. o Clinical outcome at 6 months assessed by the distribution of modified Rankin scale scores
6. o Mortality at 6 months
7. o MRI-derived quantitative measures of BBB breakdown (based on maps of the contrast agent transfer coefficient, Ktrans) in the perihematomal area at day 10 ±2 after ICH
8. o Plasma levels of inflammatory biomarkers (including MMP9, TNF alpha, IL-6 and -10, soluble TLR 2/4, Neutrophil Extracellular Traps –(NETs)) at day 10 ±2 after ICH onset
9.  The comparison of MRI-derived quantitative measures of BBB breakdown and plasma levels of inflammatory biomarkers between patients with poor vs favorable functional outcome at 6 months
10.  Performance of PET-derived quantitative measures of 18F-DPA-714 radiotracer uptake, MRI-derived quantitative measures of BBB breakdown, and plasma levels of inflammatory biomarkers to predict the functional outcome at 6 months, assessed by receiver operating characteristic (ROC) curve analyses and area under curve (AUC) values
11.  The associations of baseline clinical and imaging variables with: o PET-derived quantitative measure of 18F-DPA-714 PET radiotracer uptake o MRI-derived quantitative measures of BBB breakdown

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Delphine VERNET

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

Delphine VERNET

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications