Cord Blood Infusion for Ischemic Stroke
Primary Purpose
Stroke
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
allogeneic umbilical cord blood
Sponsored by

About this trial
This is an interventional treatment trial for Stroke focused on measuring stroke, cord blood, umbilical cord blood, hematopoietic stem cells, acute ischemic stroke
Eligibility Criteria
Inclusion Criteria:
An individual is eligible for inclusion if all of the following apply:
- Is 18-80 years old
- 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
- 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
- Subjects must have a platelet count >100,000/uL, hemoglobin >8gm/dl, and white blood cell count (wbc) >2,500/uL.
- Subjects who received tissue plasminogen activator (tPA) or underwent mechanical reperfusion may be included in the study.
- Is able to provide consent to study or consent is obtained from the subject's legally authorized 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
- 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:
- 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
- Has clinically significant and/or symptomatic hemorrhage associated with stroke
- Has new intracranial hemorrhage, edema, or mass effect that may place patient at increased risk for secondary deterioration when assessed prior to infusion
- Has hypotension as defined as the need for IV pressor support of systolic blood pressure <90
- Has isolated brain stem stroke
- Has pure lacunar stroke
- Requires mechanical ventilation
- Requires a craniotomy
- Has a serious psychiatric or neurological disease which could alter evaluation on functional or cognitive scales
- Has an active systemic infection or is HIV positive
- Has had an active malignancy within 3 years prior to the start of screening excluding skin cancers other than melanoma
- Has known coagulopathy such as Factor V Leyden, AntiPhospholipid Syndrome (APC), Protein C, Protein S deficiency, sickle cell, anticardiolipin antibody, or phospholipid syndrome
- Has any concurrent illness or condition that in the opinion of the investigator might interfere with treatment or evaluation of safety
- Has current or recent history of alcohol or drug abuse, or stroke associated with drug abuse
- Pregnant as documented by urine or blood test
Concomitant or Prior Therapies:
- Subjects currently receiving immunosuppressant drugs
- History of prior transfusion reaction
- Currently on dialysis
- Recipient of bone marrow or organ transplant
- Renal insufficiency with serum creatinine >2.0 mg/dL
- 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.
- Any previous or current treatment with angiogenic growth factors, cytokines, gene or stem cell therapy
- Subjects participating in another interventional clinical trial of an investigational therapy within 30 days of screening
Other:
- Pregnant or lactating women
- Unable to be evaluated for follow up visits
Sites / Locations
- Duke University Medical Center
- Houston Methodist
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Allogeneic Umbilical Cord Blood Infusion
Arm Description
All subjects in this study will receive an intravenous infusion of ABO/Rh matched umbilical cord blood.
Outcomes
Primary Outcome Measures
Adverse Events
Number of subjects experiencing any study related Adverse Event (AE) during the 12-month follow-up period
Graft Versus Host Disease
The proportion of subjects experiencing Graft Versus Host Disease (GVHD) at Day 100 post-infusion
Secondary Outcome Measures
Change in modified Rankin Score
The mean change in modified Rankin Score from baseline to 3 months post-infusion
Change in Infarct Volumes
Describe changes in infarct volumes over the first 3 months post-stroke
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02397018
Brief Title
Cord Blood Infusion for Ischemic Stroke
Official Title
Allogeneic Umbilical Cord Blood Infusion for Adults With Ischemic Stroke
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
May 2015 (undefined)
Primary Completion Date
February 23, 2017 (Actual)
Study Completion Date
February 23, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joanne Kurtzberg, MD
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
stroke, cord blood, umbilical cord blood, hematopoietic stem cells, acute ischemic stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Allogeneic Umbilical Cord Blood Infusion
Arm Type
Experimental
Arm Description
All subjects in this study will receive an intravenous infusion of ABO/Rh matched umbilical cord blood.
Intervention Type
Biological
Intervention Name(s)
allogeneic umbilical cord blood
Other Intervention Name(s)
cord blood, umbilical cord blood
Intervention Description
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 per kilogram. The cord blood unit will be intravenously infused into the subject over 5-30 minutes at a rate not exceeding 5 mL/kg/hr. Subjects will not receive immunosuppressive medications or any other cytoreduction prior to infusion.
Primary Outcome Measure Information:
Title
Adverse Events
Description
Number of subjects experiencing any study related Adverse Event (AE) during the 12-month follow-up period
Time Frame
12 months post-infusion for the last subject
Title
Graft Versus Host Disease
Description
The proportion of subjects experiencing Graft Versus Host Disease (GVHD) at Day 100 post-infusion
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Change in modified Rankin Score
Description
The mean change in modified Rankin Score from baseline to 3 months post-infusion
Time Frame
3 months post-infusion for the last subject
Title
Change in Infarct Volumes
Description
Describe changes in infarct volumes over the first 3 months post-stroke
Time Frame
3 months post-infusion for the last subject
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
An individual is eligible for inclusion if all of the following apply:
Is 18-80 years old
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
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
Subjects must have a platelet count >100,000/uL, hemoglobin >8gm/dl, and white blood cell count (wbc) >2,500/uL.
Subjects who received tissue plasminogen activator (tPA) or underwent mechanical reperfusion may be included in the study.
Is able to provide consent to study or consent is obtained from the subject's legally authorized 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
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:
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
Has clinically significant and/or symptomatic hemorrhage associated with stroke
Has new intracranial hemorrhage, edema, or mass effect that may place patient at increased risk for secondary deterioration when assessed prior to infusion
Has hypotension as defined as the need for IV pressor support of systolic blood pressure <90
Has isolated brain stem stroke
Has pure lacunar stroke
Requires mechanical ventilation
Requires a craniotomy
Has a serious psychiatric or neurological disease which could alter evaluation on functional or cognitive scales
Has an active systemic infection or is HIV positive
Has had an active malignancy within 3 years prior to the start of screening excluding skin cancers other than melanoma
Has known coagulopathy such as Factor V Leyden, AntiPhospholipid Syndrome (APC), Protein C, Protein S deficiency, sickle cell, anticardiolipin antibody, or phospholipid syndrome
Has any concurrent illness or condition that in the opinion of the investigator might interfere with treatment or evaluation of safety
Has current or recent history of alcohol or drug abuse, or stroke associated with drug abuse
Pregnant as documented by urine or blood test
Concomitant or Prior Therapies:
Subjects currently receiving immunosuppressant drugs
History of prior transfusion reaction
Currently on dialysis
Recipient of bone marrow or organ transplant
Renal insufficiency with serum creatinine >2.0 mg/dL
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.
Any previous or current treatment with angiogenic growth factors, cytokines, gene or stem cell therapy
Subjects participating in another interventional clinical trial of an investigational therapy within 30 days of screening
Other:
Pregnant or lactating women
Unable to be evaluated for follow up visits
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joanne Kurtzberg, M.D.
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Houston Methodist
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29752869
Citation
Laskowitz DT, Bennett ER, Durham RJ, Volpi JJ, Wiese JR, Frankel M, Shpall E, Wilson JM, Troy J, Kurtzberg J. Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase I Safety Study. Stem Cells Transl Med. 2018 Jul;7(7):521-529. doi: 10.1002/sctm.18-0008. Epub 2018 May 12.
Results Reference
result
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Cord Blood Infusion for Ischemic Stroke
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