Stem Cell Infusion in the Treatment of Patients With Neurological Complications After Ischemic Stroke

Study Overview
=================
Brief Summary
-----------------
This trial is to investigate the safety and potential therapeutic efficacy of allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) in combination with standard neurological complications after ischemic stroke treatment in Vietnam.

Detailed Description
-----------------
Stroke is the second leading cause of death behind ischemic heart disease worldwide. Traditional treatments have some limitations whereas preclinical data suggest that stem cell therapy is a promising regenerative medical treatment given the limited capacity of the central nervous system for self-repairs after ischemic stroke. Previous studies have shown that umbilical cord blood-derived Mesenchymal stem cell (UC-MSC) infusion improves the outcomes of several neurological damage conditions, including stroke. These results encouraged us to initiate the phase I/II clinical trial aiming to evaluate the safety and the efficiency of UC-MSC transplantation in the treatment of patients with neurological complications after ischemic stroke. This case-control phase I/II trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between 2021 and 2023. In this trial, 48 patients with neurological complications after ischemic stroke will be enrolled into 3 groups: UC-MSC infusion via intravenous route group (16), UC-MSC infusion via intrathecal administration route group (16), and control group (16). The UC-MSC group (IV/intrathecal) will receive two doses of thawed UC-MSC product at 1.5x106 cells/kg patient body weight with an intervention interval of three months. The primary outcome measures will include the incidence of prespecified administration-associated adverse events (AEs) and serious adverse events (SAEs). The potential efficacy will be measured using these scales including National Institutes of Health Stroke Scale-NIHSS, Functional Independence Measure -FIM, Modified Ashworth Scale-MAS, Fine motor skills-FMS, 36-Item Short Form Survey -SF-36. The clinical evaluation will be conducted at baseline and 3-, 6- and 12-months post-intervention.

Official Title
-----------------
Outcomes of Umbilical Cord Blood-derived Mesenchymal Stem Cell Infusion in Patients With Neurological Complications After Ischemic Stroke

Conditions
-----------------
Ischemic Stroke

Intervention / Treatment
-----------------
* Biological: UC-MSC infusion via intravenous route
* Biological: UC-MSC infusion via intrathecal route
* Other: standard stroke treatment and rehabilitation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Age: from 40 to 75 years. Gender: either sex Patients have been discharged/patients who are hospitalized but their general condition is stable: No need for vasopressor drugs No need for mechanical ventilation or oxygen support No signs of infection (fever, high WBC, high CRP/Procalcitonin) No kidney failure, liver failure, heart failure. Time from onset to study participation ≤ 24 months National Institutes of Health Stroke Scale (NIHSS) score >=5 Agree to participate in the study Exclusion Criteria: Hematologic cause of stroke There is evidence of active infections, failure of heart, lung, liver, or kidney, respiratory distress syndrome, anemia, clotting disorder Cancer. Pregnancy. Tracheostomy, coma, complete quadriplegia, vegetative.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UC-MSC infusion via intravenous route<br>1.5 x 10^6 umbilical Cord Mesenchymal Stem Cells per body kg will be infusion via the intravenous at baseline, and the second transplantation will be performed 3 months after the first transplantation and combination with standard frailty treatment and supplementary medication | Biological: UC-MSC infusion via intravenous route<br>* Patients assigned to UC-MSC administration groups will receive two administrations at a dose of 1.5 million cells/kg patient body weight via the intravenous (IV) route with a 3-month intervening interval<br>Other: standard stroke treatment and rehabilitation therapy<br>* Each patient can receive up to 30 days of rehabilitation therapy<br>|
| Experimental: UC-MSC infusion via intrathecal route<br>1.5 x 10^6 umbilical Cord Mesenchymal Stem Cells per body kg will be infusion via the intrathecal at baseline, and the second transplantation will be performed 3 months after the first transplantation and combination with standard frailty treatment and supplementary medication | Biological: UC-MSC infusion via intrathecal route<br>* Patients assigned to UC-MSC administration groups will receive two administrations at a dose of 1.5 million cells/kg patient body weight via the intrathecal route with a 3-month intervening interval<br>Other: standard stroke treatment and rehabilitation therapy<br>* Each patient can receive up to 30 days of rehabilitation therapy<br>|
| Other: control arm<br>standard stroke treatment and rehabilitation therapy | Other: standard stroke treatment and rehabilitation therapy<br>* Each patient can receive up to 30 days of rehabilitation therapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and serious adverse events | To assess safety, the number of AEs or SAEs during stem cell administration (72 h) at 3 months, 6 months and 12 months after discharge will be evaluated | up to the 12-month period following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale (NIHSS) score | National Institutes of Health Stroke Scale (NIHSS) scores range from 0 to 42, with higher scores indicating more severe neurological deficit | up to the 12-month period following treatment | 
| Functional Independence Measure (FIM) score | Functional Independence Measure (FIM) is a widely accepted functional assessment measure used during inpatient rehabilitation with the possible total score ranging from 18 (lowest) to 126 (highest) level of independence | up to the 12-month period following treatment | 
| Modified Ashworth Scale | The modified Ashworth scale purpose is to grade muscle spasticity. The scale is from 0 (No increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension) | up to the 12-month period following treatment | 
| Fine motor skills (FMI) score | Fine motor skills (FMI) scores range from 0 to 58 | up to the 12-month period following treatment | 
| Short Form 36 items (SF-36) score | Short Form 36 items (SF-36) consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability | up to the 12-month period following treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ischemic Stroke, umbilical cord mesenchymal stem cells, Neurological Complication