Cord Blood Infusion for Ischemic Stroke
Cord Blood Infusion for Ischemic Stroke
This is a phase one study investigating the safety of a single, intravenous infusion of
 banked allogeneic umbilical cord blood in subjects following an acute ischemic stroke. The
 cord blood infusion must be given within 3-10 days of the stroke. Follow up phone calls will
 occur at 1, 6, and 12 months post-infusion, and will include telephone surveys on post-stroke
 rehabilitation and functioning. A follow up clinic visit at 90 days will include a
 neurological exam, MRI, and blood tests.
The purpose of this study is to assess the safety of a single, intravenous infusion of banked
 allogeneic umbilical cord blood in subjects within 3-10 days following an acute ischemic
 stroke. The subjects will not be pre-treated with immunosuppressive agents. The primary
 objective is safety assessment and the secondary objectives are to determine which outcome
 measures can be used as primary and secondary endpoints for future randomized Phase 2
 clinical trials, and to describe clinical responses, if any. All subjects will receive
 standard of care acute and rehabilitation treatments while enrolled in this study.

 This is a multicenter Phase 1 safety study in patients 18-80 years of age who have sustained
 a recent ischemic stroke. A total of 10 subjects will be enrolled. Subjects will be given a
 series of baseline neurological assessments, blood tests, and MRI. Umbilical cord blood units
 will be selected from a public cord blood bank based on ABO/Rh blood type and cell dose,
 targeting a range of 0.5 to 5 x 10^7 total nucleated cells/kg. Umbilical cord blood will be
 administered intravenously as a single infusion between 3 and 10 days post-stroke. Subjects
 will be monitored for 6 hours post-infusion, and follow up will occur 24 hours later.
 Subsequent follow up phone calls will occur at 1, 6, and 12 months, and will include
 telephone surveys on post-stroke rehabilitation and functioning. A follow up clinic visit at
 90 days will include a neurological exam, MRI, and blood tests.

 Risks of cord blood infusion include infusion-related reactions such as anaphylaxis,
 urticaria, dyspnea, hypoxia, cough, wheezing, bronchospasm, nausea, vomiting, hives, fever,
 hypertension, hypotension, bradycardia, tachycardia, rigors, chills, infection, and
 hemoglobinuria. Less likely, long-term risks include transmission of infection or Graft vs
 Host Disease.
Inclusion Criteria:

 An individual is eligible for inclusion if all of the following apply:

 1. Is 18-80 years old

 2. Has had a recent (within the past 9 days), acute, cortical, hemispheric, ischemic
 stroke in the middle cerebral artery (MCA) distribution without a midline shift as
 detected by magnetic resonance imaging (MRI) as a diffusion-weighted image (DWI)
 abnormality

 3. Has a National Institutes of Health Stroke Scale (NIHSS) score of 8-15 (R) and 8-18
 (L) at the time of enrollment with no more than a 4 point increase (worsening of
 score) from the baseline score compared to 24 hours prior to infusion

 4. Subjects must have a platelet count >100,000/uL, hemoglobin >8gm/dl, and white blood
 cell count (wbc) >2,500/uL.

 5. Subjects who received tissue plasminogen activator (tPA) or underwent mechanical
 reperfusion may be included in the study.

 6. Is able to provide consent to study or consent is obtained from the subject's legally
 authorized 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. Has an ABO/Rh matched umbilical cord blood unit with a minimum of 0.5 x 10^7 total
 nucleated cells (TNCC)/kg based on the pre-cryopreservation TNCC.

 Exclusion Criteria:

 An individual is ineligible to participate if any of the following apply.

 Medical Conditions:

 1. Has a 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. Has clinically significant and/or symptomatic hemorrhage associated with stroke

 3. Has new intracranial hemorrhage, edema, or mass effect that may place patient at
 increased risk for secondary deterioration when assessed prior to infusion

 4. Has hypotension as defined as the need for IV pressor support of systolic blood
 pressure <90

 5. Has isolated brain stem stroke

 6. Has pure lacunar stroke

 7. Requires mechanical ventilation

 8. Requires a craniotomy

 9. Has a serious psychiatric or neurological disease which could alter evaluation on
 functional or cognitive scales

 10. Has an active systemic infection or is HIV positive

 11. Has had an active malignancy within 3 years prior to the start of screening excluding
 skin cancers other than melanoma

 12. Has known coagulopathy such as Factor V Leyden, AntiPhospholipid Syndrome (APC),
 Protein C, Protein S deficiency, sickle cell, anticardiolipin antibody, or
 phospholipid syndrome

 13. Has any concurrent illness or condition that in the opinion of the investigator might
 interfere with treatment or evaluation of safety

 14. Has current or recent history of alcohol or drug abuse, or stroke associated with drug
 abuse

 15. Pregnant as documented by urine or blood test

 Concomitant or Prior Therapies:

 1. Subjects currently receiving immunosuppressant drugs

 2. History of prior transfusion reaction

 3. Currently on dialysis

 4. Recipient of bone marrow or organ transplant

 5. Renal insufficiency with serum creatinine >2.0 mg/dL

 6. Hepatic insufficiency (bilirubin >2.5mg/dL or transaminases >5x the upper limit of
 normal). Patients with Gilberts syndrome are eligible for study enrollment if other
 liver function tests are normal, regardless of bilirubin level.

 7. Any previous or current treatment with angiogenic growth factors, cytokines, gene or
 stem cell therapy

 8. Subjects participating in another interventional clinical trial of an investigational
 therapy within 30 days of screening

 Other:

 1. Pregnant or lactating women

 2. Unable to be evaluated for follow up visits