RecruitingPhase 2NCT06146062

Effects of Intravascular Administration of Mesenchymal Stromal Cells Derived from Wharton's Jelly of the Umbilical Cord on Systemic Immunomodulation and Neuroinflammation After Traumatic Brain Injury.

Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

68 participants

Start Date

Jun 25, 2024

Study Type

INTERVENTIONAL

Conditions

Traumatic Brain Injury

Summary

Traumatic brain injuries (TBI) are one of the leading causes of death and disability worldwide. These patients are burdened by physical, cognitive, and psychosocial deficits, leading to an important economic impact for society. Treatments for TBI patients are limited and none has been shown to provide prolonged and long-term neuroprotective or neurorestorative effects. TBI related disability is linked to the severity of the initial injury but also to the following neuroinflammatory response which may persist long after the initial injury. Moreover, a growing body of evidence suggests a link between TBI-induced neuro-inflammation and neurodegenerative post traumatic disorders. Consequently, new therapies triggering immunomodulation and promoting neurological recovery are the subject of major research efforts. In this context, mesenchymal cell-based therapies are currently investigated to treat various neurological disorders due to their ability to modulate neuroinflammation and to promote simultaneous neurogenesis, angiogenesis, and neuroprotection. Clinical trials using intravenous MSC have been conducted for various pathologies, all these studies showing a good safety profile. The hypothesis of the study is that intravenous repeated treatment with MSC derived from Wharton's Jelly of the umbilical cord may be associated with a significant decrease of post-TBI neuroinflammation and improvement of neuroclinical status. The main objective of the study is to evaluate the effect of iterative IV injections of MSC on post-traumatic neuroinflammation measured in corpus callosum by PET-MRI at 6 months in severe brain injured patients unresponsive to simple verbal commands 5 days after sedation discontinuation.

Eligibility

Min Age: 18 YearsMax Age: 50 Years

Inclusion Criteria11

healthy volunteers will be included for MRI normalization Volunteer eligibility criteria
Age 18-50 years
ASA 1 classification (healthy patient)
Age 18-50 years
Severe TBI defined by:
Glasgow score \<12 within the 48 first hours,
Brain traumatic lesion on CT scan,
Need for intracranial pressure monitoring
No other significant organ trauma (AIS \<2)
Unresponsive to verbal commands 5 days after sedation discontinuation, for whom, after usual clinical and paraclinical evaluation there has been no decision to interrupt active therapies within 10 days after sedation discontinuation
Written consent signed by the close relative

Exclusion Criteria41

Lack of written consent
Neurological history likely to alter the image (epilepsy, transient ischaemic attack, meningitis, head trauma)
Vulnerable person according to article L1121-6 of the CSP
Protected adult person
No affiliation to a social security regime
Pregnancy
Contraindication for MRI and PET-MRI
patients with Pacemaker and defibrillator
MR-incompatible prosthetic heart valve
Metallic intraocular, intra cerebral or intra medullary foreign bodies
Implantable neurostimulation systems
Cochlear implants/ear implant
Metallic fragments such as bullets, shotgun pellets, and metal shrapnel
Cerebral artery aneurysm clips
Ventriculo peritoneal shunt with metallic component generating significant artefacts on the MR sequence
Catheters with metallic components (Swan-Ganz catheter)
Patient unable to remain supine and motionless during the duration of the examination
History of disease or treatment impairing current or previous year immunity function ( hematologic disease (leukemia, myeloma), viral disease affecting immunity (like HIV), immunological treatment (corticoid, anti rejection medication, anti TNFα, chemotherapy)
History of severe neurological or psychiatric disease likely to alter neurological assessment
HTAP \> grade III OMS/WHO
Ongoing uncontrolled infection with organ failure (septic shock, ARDS) including those due to severe COVID-19
Platelets \<100 G/L or \<100000/μL, Hb \<8 g/dL, lymphocytes count \<1.5 G/L or 1500 μL , neutrophils count \< 2.5G/L or \<2500/μL, , creatinin \> 100 μmol/L
Liver function abnormalities (bilirubin\> 2.5mg / dL or transaminases\> 5x the ULN). Patients with Gilbert's disease are eligible if liver tests are normal excluding bilirubinemia
Known HIV seropositivity
Neoplasia ongoing or treated in the 3 years before screening
Bone marrow transplant recipient
History of transfusion reaction or hypersensitivity
Pregnancy
Contraindication for MRI and PET-MRI:
Patient with Pacemaker and defibrillator
MR-incompatible prosthetic heart valve o Metallic intraocular, intra cerebral or intra medullary foreign bodies
Implantable neurostimulation systems o Cochlear implants/ ear implant
Metallic fragments such as bullets, shotgun pellets, and metal shrapnel
Cerebral artery aneurysm clips
Ventriculo peritoneal shunt with metallic component generating significant artefacts on the MR sequence
Catheters with metallic components (Swan-Ganz catheter)
Patient unable to remain supine and motionless during the duration of the examination
Participation in another interventional clinical trial of an investigational therapy within 30 days of consent
No affiliation to a social security regime
Vulnerable person according to article L1121-6 of the CSP
Protected adult person