Study of Allogeneic Umbilical Cord Blood Infusion for Adults With Ischemic Stroke
Condition: Stroke; Stroke, Acute; Brain Injury, Acute
MeSH terms: Stroke; Brain Injuries; Ischemic Stroke
Intervention: Umbilical Cord Blood; Placebo
Intervention description: 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 79.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: hematopoietic stem cells; umbilical cord blood; stroke; ischemic stroke

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:

          1. 18-90 years old

          2. 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.

          3. 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.

          4. 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.

          5. Subjects who received tPA (Tissue plasminogen Activator) or underwent endovascular
             reperfusion may be included in the study

          6. Able to provide consent to study or consent is obtained from the patient's legal
             representative

          7. 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

          8. Is a good candidate for the trial, in the opinion of the Investigator

          9. Agrees to participate in follow-up visits

         10. 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

         11. Has not had a disease or therapy that would compromise current immune function.

         12. 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:

          1. 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

          2. Clinically significant and/or symptomatic hemorrhage associated with stroke

          3. 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

          4. New intracranial hemorrhage, edema, or mass effect that may place patient at increased
             risk for secondary deterioration when assessed prior to infusion

          5. Hypotension as defined as the need for IV pressor support of SBP (systolic blood
             pressure) <90

          6. Isolated brain stem stroke

          7. Pure lacunar stroke

          8. At time of consent, patients who are mechanically ventilated or, at the investigator's
             discretion are felt to be likely to need mechanical ventilation are excluded.

          9. Requires a craniotomy

         10. Serious psychiatric or neurological disease which could alter evaluation on functional
             or cognitive scales

         11. Active systemic infection that is felt, at the discretion of the Investigator, to
             place the patient at increased risk for participation in this study

         12. Documentation of human immunodeficiency virus positive (HIV+) status in the medical
             record

         13. Active malignancy within 3 years prior to the start of screening excluding skin
             cancers other than melanoma

         14. Known hypercoagulable state or coagulopathy deficiencies such as Factor V Leiden,
             Antiphospholipid Syndrome (APC), Protein C, Protein S, anticardiolipin antibody,
             phospholipid syndrome or Sickle Cell Disease

         15. History of or currently active autoimmune disease, or current immunomodulatory therapy
             or a recipient of immunomodulatory therapy in the past year.

         16. Concurrent illness or condition that in the opinion of the Investigator might
             interfere with treatment or evaluation of safety

         17. Current or recent history of alcohol or drug abuse, or stroke associated with drug
             abuse that Investigator feels may impair therapy or assessments

         18. Pregnant as documented by blood test

        Prohibited Concomitant or Prior Therapies

          1. Patients currently receiving immunosuppressant drugs, not including glucocorticoid
             taper, topical/inhaled glucocorticoids

          2. History of prior transfusion reaction

          3. Currently on dialysis

          4. Recipient of bone marrow or organ transplant

          5. Hepatic insufficiency (bilirubin >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

          6. Previous or current treatment with angiogenic growth factors, cytokines, gene or stem
             cell therapy

          7. Participating in another interventional clinical trial of an investigational therapy
             within 30 days of consent.

        Other Exclusion Criteria

          1. Pregnant or lactating women

          2. Unable or unwilling to be evaluated for follow-up visits