The primary objective of this study is to determine the efficacy of a single intravenous infusion of unrelated donor umbilical cord blood (UCB) for improving functional outcomes in patients with ischemic stroke. Eligible subjects will receive an intravenous infusion of UCB or placebo 3-10 days following stroke. Subjects will not receive immunosuppressive or myeloablative medications prior to the infusion. Subjects will be followed for one year post infusion for safety and efficacy. Assessments will examine safety and tolerability of the infusion, change in neurological symptoms, change in quality of life, and emotional and cognitive status. Assessments will occur at 24 hours post infusion, and at 30, 90, 180 and 365 days post infusion.
This is a multicenter, placebo controlled, randomized, double blinded Phase 2 study in 100 subjects 18-90 years of age who have sustained a recent ischemic stroke. Potential subjects can be screened and consented the day of their stroke (Day 1). Treatment with umbilical cord blood (UCB) cells or placebo will be administered intravenously as a single infusion as early as 3 days but no later than 10 days after the patient's stroke. UCB units will be selected from an accredited U.S. public cord bank based on blood type, race and a targeted cell dose ranging between 0.5 to 5 x 10^7 total nucleated cell count (TNCC)/kg. Study subjects will not receive immunosuppressive or myeloablative medications prior to infusion of the cord blood or placebo.
All subjects, families and medical staff will be blinded to treatment arm. When a subject is randomized to study drug at a clinical site without a cord blood bank, the selected cord blood units (CBU) will be shipped frozen overnight to the site. Once selected and available on site, each CBU will be thawed, washed, tested, released and infused intravenously using common standard operating procedures (SOPs) at all sites. For subjects randomized to placebo, a diluent with the same appearance and odor as a CBU will be prepared.
Patients will have baseline magnetic resonance imaging (MRI) and will be assessed at 1, 3, 6, and 12 months for functional outcomes. All patients will receive standard of care therapy while enrolled in this study and all subjects will be strongly encouraged to participate in rehabilitative therapy.
The primary objective of the study is to determine, in a randomized, placebo controlled trial, the efficacy of a single intravenous (IV) infusion of unrelated donor UCB for improving functional outcomes in patients with ischemic stroke. The secondary objectives are as follows:
1. To describe the safety and tolerability of a single IV infusion of unrelated donor UCB in patients with ischemic stroke
2. To evaluate the efficacy of a single IV infusion of unrelated donor UCB for improvement of neurological symptoms following ischemic stroke
3. To evaluate the efficacy of a single IV infusion of unrelated donor UCB for improvement in quality of life and emotional and cognitive status in patients with ischemic stroke
- Placebo Drug
Intervention Desc: The placebo product will be acellular and will consist of tissue culture medium 199 (TC-199 [pink]) with 1% dimethyl sulfoxide (DMSO), which are standard components in cellular products. The volume of placebo product will be 50 mL, which is in the range of a typical UCB unit that has been washed and thawed after cryopreservation. Infusion and premedication procedures will be the same as those conducted for the umbilical cord blood arm. ARM 1: Kind: Experimental Label: Placebo Description: A single intravenous infusion of diluent with the same appearance and odor as a cord blood unit within 3-10 days following stroke.
- Umbilical Cord Blood Biological
Other Names: cord blood, hematopoietic stem cells Intervention Desc: Umbilical cord blood will be infused intravenously through a peripheral IV line after premedication with diphenhydramine, hydrocortisone, and acetaminophen. Units will be from a public cord blood bank with selection based on blood type, race, and the number of cells in the pre cryopreservation product, targeting a dose range of 0.5 to 5 x 10^7 TNCC/kg. ARM 1: Kind: Experimental Label: Umbilical Cord Blood Description: A single intravenous infusion of umbilical cord blood within 3-10 days following stroke.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Shift in modified Rankin Scale (mRS)||3 months post infusion|
|Secondary||Incidence and severity of infusion reactions||1 year post infusion|
|Secondary||Incidence and severity of product-related infections||1 year post infusion|
|Secondary||Incidence of alloimmunization||1 year post infusion|
|Secondary||Incidence and severity of graft vs. host disease||1 year post infusion|
|Secondary||Incidence and severity of study related and unexpected AEs||1 year post infusion|
|Secondary||Mortality||1 year post infusion|
|Secondary||Functional independence||90 days post infusion|
|Secondary||mRS shift||30 days post infusion|
|Secondary||NIHSS||90 days post infusion|
|Secondary||Barthel Index||90 days post infusion|
|Secondary||Stroke Impact Scale||90 days post infusion|
|Secondary||European Quality of Life||90 days post infusion|
|Secondary||Patient Health Questionnaire Scale||90 days post infusion|
|Secondary||Telephone Interview for Cognitive Status||30 days post infusion|
|Secondary||Trail Making Test||90 days post infusion|
|Secondary||Montreal cognitive Assessment (MoCA)||90 days post infusion|
|Secondary||Hopkins Verbal Learning Test-Revised (HVLT-R)||90 days post infusion|
|Secondary||Patient Health Questionnaire (PHQ-8)||90 days post infusion|
|Secondary||Short Form 36 Health Survey (SF-36)||90 days post infusion|
|Secondary||Controlled Oral Word Association test (COWAT)||90 days post infusion|
|Secondary||Oral Symbol Digit Modalities Test (SDMT)||90 days post infusion|