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.

NCT06146062 | Recruiting Phase 2 DMC

• 2 other identifiers: APHP2115092021-006873-50
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (27)

• radiological markers from PET-MRI_1

  6 months after the last injection

• radiological markers from PET-MRI_2

  6 months after the last injection

• Treatment feasibility

  at the third injection

• Neurological clinical Score M6

  6 months after the last injection

• Neurological clinical Score M12

  12 months after the last injection

Other Outcomes (10)

• Analyze the pharmacokinetics and pharmacodynamics of CSM WJ-UC in humans 1

  After 3rd injection 48 hours later

• Analyze the pharmacokinetics and pharmacodynamics of CSM WJ-UC in humans 2

  After 3rd injection 48 hours later

• Deep phenotyping of the main immune effector cell populations humans, to identify the phenotypes involved in immunomodulation and alloimmunization induced by MSC administration. 1

  After 3rd injection 48 hours later

Study Arms (2)

Intervention

EXPERIMENTAL

Final product is a MSC solution at the concentration of 2.10\^6/kg in 150 mL of NaCl 0.9% and human albumin 0.5%, conditioned aseptically and identified for IV administration. 3 injections one week apart.

Drug: Mesenchymal Stromal Cells (MSC)

control

PLACEBO COMPARATOR

The placebo will be a solution of NaCl 0.9% 3 injections one week apart.

Drug: placebo

Interventions

Mesenchymal Stromal Cells (MSC) DRUG

3 injections one week apart

Intervention

placebo DRUG

3 injections one week apart

control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-50 years
• ASA 1 classification (healthy patient)

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (3)

Hôpital National d'Instruction des Armées Percy

Clamart, France

RECRUITING

Beaujon Hospital

Clichy, France

RECRUITING

Hôpital de la Pitié Salpêtrière - AP-HP

Paris, France

RECRUITING

Related Publications (1)

• Sigaut S, Tardivon C, Jacquens A, Bottlaender M, Gervais P, Habert MO, Monsel A, Roquilly A, Boutonnet M, Galanaud D, Cras A, Boucher-Pillet H, Florence AM, Cavalier I, Menasche P, Degos V, Couffignal C. 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 (TRAUMACELL): study protocol for a multicentre randomised controlled trial. BMJ Open. 2024 Dec 31;14(12):e091441. doi: 10.1136/bmjopen-2024-091441.

  PMID: 39740941 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Vincent DEGOS

  APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent Degos

CONTACT

142163761; vincent.degos@aphp.fr

Stéphanie Sigaut

CONTACT

140875009; stephanie.sigaut@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: use of placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: November 24, 2023
• Study Start: June 25, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)