Phase 2
N=79
Study of Allogeneic Umbilical Cord Blood Infusion for Adults With Ischemic Stroke
Stroke · Stroke, Acute · Brain Injury, Acute
Bottom Line
View on ClinicalTrials.gov: NCT03004976 ↗Enrolled (actual)
79
Serious AEs
31.7%
Results posted
Sep 2022
Primary outcome: Primary: Shift in Modified Rankin Scale (mRS) — 1; 1 score on a scale — p=0.71
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Umbilical Cord Blood (Biological); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Joanne Kurtzberg, MD
- Primary completion
- Jul 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Shift in Modified Rankin Scale (mRS) |
1; 1 | 0.71 |
| SECONDARY Number of Infusion Reactions |
13; 4 | — |
| SECONDARY Number of Product-related Infections |
0; 0 | — |
| SECONDARY Number of Alloimmunization Events |
0; 0 | — |
| SECONDARY Number of Graft vs. Host Disease Events |
0; 0 | — |
| SECONDARY Number of Study Related and Unexpected Adverse Events (AEs) |
0; 0 | — |
| SECONDARY Mortality |
4; 1 | — |
| SECONDARY Number of Participants With Functional Independence |
15; 6 | — |
| SECONDARY Shift in Modified Rankin Scale (mRS) From Baseline to 30 Days Post Infusion |
1; 1 | — |
| SECONDARY Shift in Modified Rankin Scale (mRS) From Baseline to 180 Days Post Infusion |
1; 1 | — |
| SECONDARY The National Institutes of Health Stroke Scale (NIHSS) Score at 90 Days |
6; 6 | — |
| SECONDARY Barthel Index (BI) Score at 90 Days |
80; 85 | — |
| SECONDARY Stroke Impact Scale-16 (SIS-16) Score at 90 Days |
59; 64 | — |
| SECONDARY The European Quality of Life (EQ-5D-3L) Visual Analogue Score (VAS) at 90 Days |
70; 75 | — |
| SECONDARY Patient Health Questionnaire Scale (PHQ 8) Score at 90 Days |
4; 5 | — |
| SECONDARY Telephone Interview for Cognitive Status (TICS) Total Score at 30 Days Post Infusion |
27; 21 | — |
| SECONDARY Telephone Interview for Cognitive Status (TICS) Total Score at 1 Year Post Infusion |
31; 30 | — |
| SECONDARY Trail Making Test Score at 90 Days Post Infusion (Trail A) |
78; 62 | — |
| SECONDARY Trail Making Test Score at 90 Days Post Infusion (Trail B) |
278; 300 | — |
| SECONDARY Montreal Cognitive Assessment (MoCA) Score at 90 Days Post Infusion |
21; 20 | — |
| SECONDARY Hopkins Verbal Learning Test-Revised (HVLT-R) Score at 90 Days Post Infusion |
15; 12 | — |
| SECONDARY Short Form 36 Health Survey (SF-36) Scores at 90 Days Post Infusion |
30; 60; 0; 0; 66.7; 100 | — |
| SECONDARY Controlled Oral Word Association Test (COWAT) Score at 90 Days Post Infusion |
14; 9.5 | — |
| SECONDARY Oral Symbol Digit Modalities Test (SDMT) Score at 90 Days Post Infusion |
13; 21 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- 18-90 years old
- Recent, acute, cortical, hemispheric, ischemic stroke in the MCA (middle cerebral artery) distribution without a clinically significant midline shift as detected by MRI as a DWI (diffusion-weighted imaging) abnormality. If unable to obtain a MRI scan, patients may be included if there is clear evidence of ischemic cortical involvement in the MCA distribution demonstrated by computed tomography and a clinical exam consistent with cortical involvement.
- NIHSS 6-15 (R) and 6-20 (L) at the time of informed consent. Subjects with a >4-point increase of NIHSS from time of consent (worsening of score) will not be eligible for infusion.
- Subjects must have a platelet count >100,000/uL, hemoglobin >8gm/dL, absolute lymphocyte count (ALC) ≥ 1200 for African American patients and ≥1500 for all other racial-ethnic groups, and WBC (white blood cell) count >2,500/uL OR Historical pre-stroke value of ALC ≥ 1200 for African American and ≥1500 for all other racial-ethnic groups within 6 months of stroke
-And- a post stroke ALC value of ≥ 1000, platelet count >100,000/uL, hemoglobin >8gm/dL and WBC >2,500/uL.
- Subjects who received tPA (Tissue plasminogen Activator) or underwent endovascular reperfusion may be included in the study
- Able to provide consent to study or consent is obtained from the patient's legal representative
- Subjects of childbearing potential must practice effective contraception during the study, and be willing to continue contraception for at least 6 months after intervention so that, in the opinion of the Investigator, they will not become pregnant during the course of the study
- Is a good candidate for the trial, in the opinion of the Investigator
- Agrees to participate in follow-up visits
- ABO/Rh and race matched CBU(s) with a minimum of 0.5 x 10^7 TNCC/kg based on the pre-cryopreservation TNCC is available for infusion
- Has not had a disease or therapy that would compromise current immune function.
- Has a serum creatinine ≤2 mg/dL OR Glomerular Filtration Rate (GFR) ≥30mL/min
Exclusion Criteria
An individual is ineligible to participate if any of the following apply:
Exclusionary Medical Conditions:
- Medical history of neurological or orthopedic pathology with a deficit as a consequence that results in a modified Rankin Scale >1 before stroke or has a pre existing cognitive deficit
- Clinically significant and/or symptomatic hemorrhage associated with stroke
- Evidence of significant midline shift as assessed by CT or MRI who are felt to be at high risk for neurological decompensation or need for decompressive hemicraniectomy due to hemispheric edema
- New intracranial hemorrhage, edema, or mass effect that may place patient at increased risk for secondary deterioration when assessed prior to infusion
- Hypotension as defined as the need for IV pressor support of SBP (systolic blood pressure) 2.5mg/dL or transaminases >5x the ULN) Patients with Gilberts syndrome are eligible for study enrollment if other liver function tests are normal, regardless of bilirubin level
- Previous or current treatment with angiogenic growth factors, cytokines, gene or stem cell therapy
- Participating in another interventional clinical trial of an investigational therapy within 30 days of consent.
Other Exclusion Criteria
- Pregnant or lactating women
- Unable or unwilling to be evaluated for follow-up visits
Data sourced from ClinicalTrials.gov (NCT03004976). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.