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.

Traumatic Brain Injury Clinical Trial

— TRAUMACELL  

Official title:

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06146062
• Other study ID #: APHP211509
• Secondary ID: 2021-006873-50
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 18, 2024
• Est. completion date: March 31, 2028

Study information

• Verified date: June 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Vincent Degos
• Phone: 142163761
• Email: vincent.degos[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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. Indeed, several experimental studies have reported that human umbilical cord-derived mesenchymal stromal cells (MSC) have the ability to improve neurological outcomes and recovery in cerebral injury animal models, including TBI.

Clinical trials using intravenous MSC have been conducted for various pathologies, all these studies showing a good safety profile. In TBI, small clinical trials using different modalities for administration of mesenchymal cells are available but none about MSC derived from Wharton's Jelly of the umbilical cord.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 68
• Est. completion date: March 31, 2028
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

20 healthy volunteers will be included for MRI normalization

Inclusion Criteria:

• Age 18-50 years

• Severe TBI defined by:

• Glasgow score <12 within the 48 first hours,

• brain 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 Criteria:

• History of disease or treatment impairing current or previous year immunity function

• 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 <100G/L, Hb <8 g/dL, lymphocytes count <1.5 G/L, neutrophils count <2.5G/L, 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

• 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

• 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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Drug:
• Mesenchymal Stromal Cells (MSC)
3 injections one week apart
• placebo
3 injections one week apart

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effect of iterative IV injections of WJ-UC-MSC on post-traumatic neuroinflammation	[18F]-DPA-714 Standard Uptake Value ratio (SUVr) in corpus callosum (Region of Interest, ROI) measured by dynamic PET-MRI	6 months after the last injection
Secondary	radiological markers from PET-MRI_1	The regional fractional anisotropy (FA) from DTI acquisition of PET-MRI	6 months after the last injection
Secondary	radiological markers from PET-MRI_2	The mean diffusibility (MD) from DTI acquisition of PET-MRI	6 months after the last injection
Secondary	Treatment feasibility	number of treatments administrated to the patient	at the third injection
Secondary	Neurological clinical Score M6	Glasgow Outcome Scale-Extended	6 months after the last injection
Secondary	Neurological clinical Score M12	Glasgow Outcome Scale-Extended	12 months after the last injection
Secondary	cognitive assessment M6	MOCA scale	6 months after the last injection
Secondary	cognitive assessment M12	MOCA scale	12 months after the last injection
Secondary	short term Tolerance D10	Common Terminology Criteria for Adverse Events	10 days after the last injection
Secondary	long term Tolerance M6	Common Terminology Criteria for Adverse Events	6 months after the last injection
Secondary	long term Tolerance M12	Common Terminology Criteria for Adverse Events	6 months after the last injection