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

In this prospective, multicenter study of patients with acute spontaneous supratentorial Intracerebral Hemorrhage (ICH), each participant will have a standardized multimodal evaluation of neuroinflammation at 10 (±2) days after onset including translocator protein 18 kDa (TSPO) positron emission tomography (PET) using 18F-DPA-714 radioligand, BBB imaging using Dynamic contrast-enhanced (DCE)-MRI and a panel of pro-inflammatory and anti-inflammatory plasma biomarkers.

Study Overview

• Status: Not yet recruiting
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: TEP with 18F-DPA-714 injection

Detailed Description

Intracerebral Hemorrhage (ICH) is the most devastating stroke subtype that affects > 3 million people worldwide each year. Despite important efforts and the hope that minimally invasive surgical procedures may offer, there is currently no effective treatment. Perihematomal edema - a surrogate marker of neuroinflammation - has emerged as important contributors to poor functional outcome following acute ICH, and a potential treatment target. Innovative techniques have been developed to image and measure neuroimmune response (TSPO PET) and BBB integrity (DCE-MRI). These novel methods have been poorly studied in ICH. The effects of in vivo perihematomal neuroinflammation on the functional outcome of patients with acute ICH is widely unknown.

The present study is a prospective, multicenter study of patients with acute spontaneous supratentorial ICH (within 48h after onset). Each participant will have a standardized multimodal evaluation of neuroinflammation at 10 days after onset including TSPO PET using 18F-DPA-714 radioligand, BBB imaging using DCE-MRI and a panel of pro-inflammatory and anti-inflammatory plasma biomarkers.

In hospital follow up visit will occur at 14 days and end of follow up visit at 180 days. Functional outcome will be assessed by modified Rankin scale (mRS), which is a widely used and validated scale - ranging from 0 (no symptoms) to 6 (death) - to evaluate the functional outcome following ischemic or hemorrhagic strokes.

• Study Type: Interventional
• Enrollment (Estimated): 117
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nicolas RAPOSO, MD, PHD; Phone Number: 33 05 61 77 76 40; Email: raposo.n@chu-toulouse.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • Chu de Bordeaux
    • Contact: Igor Sibon, MD, PHD; Phone Number: 33 .5.56.79.55.20; Email: igor.sibon@chu-bordeaux.fr
  • Montpellier, France, 34000
    • CHU de Montpellier
    • Contact: Adrien Ter Schiphorst, MD; Phone Number: 33 .4.67.33.67.33; Email: adrien.ter.schiphorst@gmail.com
  • Toulouse, France, 31000
    • CHU de Toulouse
    • Contact: Nicolas Raposo, MD, PHD; Phone Number: 33 5 61 77 76 40; Email: raposo.n@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Massive ICH volume (≥ 60 ml) at admission;
2. Severe coma (defined as a Glasgow Coma Scale score < 6) at admission;
3. Planned neurosurgical hematoma evacuation;
4. Decision already taken for palliative care with withdrawal of active treatment;
5. Pre-existing dependance defined as a mRS score ≥2 prior to ICH occurrence;
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. TSPO genotyping demonstrating a low affinity binder profile,
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. Estimated glomerular filtration rate < 30 ml/min/1.73 m 2
10. Unable to tolerate or contraindicated to 18F-DPA714 PET: women who are pregnant or breastfeeding, claustrophobia, and known hypersensitivity to DPA-714;
11. Use of Benzodiazepines within 7 days (within 6 weeks for prazepam, diazepam or clorazepate) preceding TSPO PET acquisition;
12. Co-existing neuroinflammatory disease such as Multiple Sclerosis, Neuromyelitis optica, Neurosarcoidosis, autoimmune encephalitis, CNS vasculitis;
13. Conditions requiring long-term immunosuppressive medication;
14. Expected impossible follow-up or poor compliance;
15. Patient under tutorship, curatorship, or legal protection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 18F-DPA-714 PET radiotracer uptake within the perihematomal edema; 18F-DPA-714 injection for TEP	Drug: TEP with 18F-DPA-714 injection; TEP with 18F-DPA-714 injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the functional outcome (poor versus favorable) at 6 months	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.; 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	o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o The functional outcome is measured at 6 months after ICH

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume of brain tissue with increased 18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the functional outcome (poor versus favorable) at 6 months	18F-DPA-714 binding is measured by the mean standard uptake value ratio (SUVR). Volume of brain tissue (mL) with increased 18F-DPA-714 binding is measured in the area around the hematoma.; 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	o 18F-DPA-714 binding is measured at day 10 ±2 after ICH o The functional outcome is measured at 6 months after ICH
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the occurrence of neurological deterioration within 14 days after ICH onset	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.; Neurological deterioration within 14 days after ICH onset is defined as a ≥4-point increase on the National Institutes of Health Stroke Scale (NIHSS) or ≥2-point decrease on the Glasgow Coma Scale (GCS) compared to baseline scores at the pre-inclusion visit	o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o Neurological deterioration is assessed within 14 days after ICH onset
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the occurrence of early death	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.; Early death is defined as death at day 30 after ICH onset.	o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o Early death is assessed within 30 days after ICH onset.
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the clinical outcome at 6 months	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.; Clinical outcome at 6 months is assessed by the distribution of modified Rankin scale scores	o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o Clinical outcome is assessed et 6 months
18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH according to the mortality	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.; Mortality is assessed at 6 months.	o 18F-DPA-714 binding is measured at day 10 ±2 after ICH. o Mortality is assessed at 6 months.
Correlations of 18F-DPA-714 PET radiotracer uptake at day 10 ±2 after ICH with MRI-derived measures of BBB breakdown and plasma levels of inflammatory biomarkers	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.; BBB breakdown is quantified by MRI-derived quantitative measures based on maps of the contrast agent transfer coefficient (Ktrans) in the perihematomal area at day 10 ±2 after ICH;; Plasma levels of inflammatory biomarkers (including MMP9, TNF alpha, , IL-6 and -10, soluble TLR 2/4, Neutrophil Extracellular Traps (NETs) are measured at day 10 ±2 after ICH onset.	PET, MRI and plasma inflammatory biomarkers measures are evaluated at day 10 ±2 after ICH onset
BBB breakdown at day 10 ±2 after ICH according to the functional outcome (poor versus favorable) at 6 months	BBB breakdown is quantified by MRI-derived quantitative measures based on maps of the contrast agent transfer coefficient (Ktrans) in the perihematomal area at day 10 ±2 after ICH;; 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	o MRI-derived quantitative measures of BBB breakdown are assessed at day 10 ±2 after ICH. o The functional outcome is measured at 6 months after ICH.
Plasma levels of inflammatory biomarkers at day 10 ±2 after ICH according to the functional outcome (poor versus favorable) at 6 months	Plasma levels of inflammatory biomarkers (including MMP9, TNF alpha, , IL-6 and -10, soluble TLR 2/4, Neutrophil Extracellular Traps (NETs) are measured at day 10 ±2 after ICH onset;; 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	o Plasma inflammatory biomarkers measures are assessed at day 10 ±2 after ICH. o The functional outcome is measured at 6 months after ICH.

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 26, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hemorrhage; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Cerebral Hemorrhage; tetraethylpyrazine
• Other Study ID Numbers: RC31/24/0443; 2025-521923-58-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No