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.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 68
- 试验地点
- 3
- 主要终点
- effect of iterative IV injections of WJ-UC-MSC on post-traumatic neuroinflammation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
use of placebo
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Intervention
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.
干预措施: Mesenchymal Stromal Cells (MSC) (Drug)
control
The placebo will be a solution of NaCl 0.9% 3 injections one week apart.
干预措施: placebo (Drug)
结局指标
主要结局
effect of iterative IV injections of WJ-UC-MSC on post-traumatic neuroinflammation
时间窗: 6 months after the last injection
\[18F\]-DPA-714 Standard Uptake Value ratio (SUVr) in corpus callosum (Region of Interest, ROI) measured by dynamic PET-MRI
次要结局
- cognitive assessment M12(12 months after the last injection)
- Neurological clinical Score M6(6 months after the last injection)
- neuroinflammation of pericontusional(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 M12(12 months after the last injection)
- cognitive assessment M6(6 months after the last injection)
- radiological markers from PET-MRI_1(6 months after the last injection)
- short term Tolerance D10(10 days after the last injection)
- long term Tolerance M6(6 months after the last injection)
- long term Tolerance M12(6 months after the last injection)
- neuroinflammation of grey matter(6 months after the last injection)
- neuroinflammation of white matter(6 months after the last injection)
- neuroinflammation of frontal area(6 months after the last injection)
- neuroinflammation of parietal area(6 months after the last injection)
- neuroinflammation of occipital area(6 months after the last injection)
- neuroinflammation of hippocampus(6 months after the last injection)
- neuroinflammation of thalamus(6 months after the last injection)
- neuroinflammation of mesencephalus(6 months after the last injection)
- neuroinflammation of cerebellum(6 months after the last injection)
- Cytokine and chemokine levels in plasma(6 months after the last injection)
- PBMC profile(6 months after the last injection)
- Transcriptomics and regulatory epigenomics of circulating monocytes and lymphocytes 1.(6 months after the last injection)
- Transcriptomics and regulatory epigenomics of circulating monocytes and lymphocytes 2.(6 months after the last injection)
- Transcriptomics and regulatory epigenomics of circulating monocytes and lymphocytes 3.(6 months after the last injection)
- Transcriptomics and regulatory epigenomics of circulating monocytes and lymphocytes 4.(6 months after the last injection)
- Genome-wide single-nucleotide polymorphism (SNP) genotype.(After 1 injection)