Back to resultsSafety of Autologous Human Umbilical Cord Blood Treatment for Perinatal Arterial Ischemic Stroke
Primary Purpose
Perinatal Arterial Ischemic Stroke
Status
Suspended
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous Cord Blood Infusion
Sponsored by
About this trial
This is an interventional treatment trial for Perinatal Arterial Ischemic Stroke
Eligibility Criteria
Inclusion Criteria:
- Between 6 weeks and 6 years of age on the day of study cord blood infusion.
- MRI documented single arterial distribution infarction.
- Initial injury occurring in the prenatal or perinatal period
- Ability of child and caregiver to travel to Orlando, and stay for at least 4 days, and to return for all Follow-up visits (patient is responsible for cost of travel and lodging while in Orlando)
Exclusion Criteria:
- Inability to obtain all pertinent medical records, including pertinent physician notes, laboratory findings, and radiographic images, related to the original injury, hospitalization and rehabilitation - must be sent to FHFC research team 14 days prior to scheduled study cord blood treatment. Need brain MRI with flair sequence <2 weeks old.
- Recent radiographic evidence (imaging performed within past 2 weeks) of extensive stroke as evidenced by >100ml lesion
- Multifocal infarctions on screening MRI.
- Evidence of hypoxic-ischemic encephalopathy on screening MRI.
- Uncorrected coagulopathy during the baseline period defined as INR > 1.4; PTT> 35 sec; PLT < 100,000
Known history of:
- Recently diagnosed infection (within past 2 weeks) requiring treatment and/or medical intervention
- Renal disease or altered renal function as defined by serum creatinine >1.5 mg/dL at admission
- Hepatic disease or altered liver function as defined by SGPT > 150 U/L, and/or T. Bilirubin >1.3 mg/dL at enrollment
- Malignancy
- Immunosuppression as defined by WBC < 3 (10x3) at admission
- HIV
- Any evidence of active maternal infection during the pregnancy (Hepatitis A, Hepatitis B, Hepatitis C, HIV 1, HIV 2, Human T-lymphotropic Virus (HTLV) 1, HTLV 2
- Pneumonia, or chronic lung disease requiring oxygen
- Cord blood sample contamination
- Participation in a concurrent intervention study
- Desire for organ-donation in the event of death
- Unwillingness or inability to stay for at least four days following cord blood infusion (should any problems arise following the infusion) and to return for 6 month, and 1 year follow-up visits
Sites / Locations
- Florida Hospital for Children
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cord Blood Infusion
Arm Description
Autologous cord blood infusion
Outcomes
Primary Outcome Measures
Composite Outcome: Hemodynamic Safety
Three primary and two secondary hemodynamic indices will be monitored as indices of hemodynamic stability throughout the infusion and post-infusion periods. Heart rate, blood pressure, and oxygen saturation will be recorded every 5 minutes during the infusion, every 30 minutes for 2 hours after infusion and then hourly for 6 hours. A consistent, non-isolated 20% decrease in any of these indices will be prompt additional maneuvers to restore MAP.
Two secondary hemodynamic indices will be monitored as indices of hemodynamic stability: capillary refill and heart rate. Prolongation of capillary refill by 2 seconds from baseline and/or >20% change in heart rate during the procedure will prompt an evaluation as to the etiology of the change in hemodynamic status. An adverse event will be defined as a sustained (> 10 minutes) >20% decrease in MAP. Transient decreases in MAP that respond to fluid infusion or inotropes will not be considered adverse events.
Composite Outcome: Pulmonary Safety
A concern exists regarding the systemic infusion of leukocytes in a concentrated manner. Theoretically, activated monocytes could function to enhance PMN migration into the lung, as the lung is the primary "first pass" filter for intravenous infusion of any cellular product. PMN mediated organ injury typically occurs over a 6-24 hour time frame. Based on this, Chest radiographs will be performed and evaluated at Baseline and on Post-Infusion Day 1. Chest radiographs will be evaluated for systemic infusion of leukocytes in a concentrated manner. Additionally, blood-oxygen saturation will be monitored by finger oximeter. Moderate respiratory dysfunction within the first 48 hours post infusion will be considered an adverse event but will not warrant stopping the trial unless recommended by the DSMB. In the event of pulmonary dysfunction, standard supportive therapy will be given. Pulmonary symptoms/events corresponding to the CTCAE v3.0 Grade 3 will trigger the stopping rules.
Composite Outcome: Renal Safety
To minimize the effect of DSMO, our hUCB product will be washed according to Standard Operating Procedures prior to infusion. Though unlikely, it is possible that some quantity of DMSO will remain which could cause toxicity. Renal function/events corresponding to the CTCAE v3.0 Grade 3 will trigger the stopping rules
Composite Outcome: Neurological Safety
The patient's acute neurologic status will be monitored until discharged. Data recorded every 4 hours includes GCS, pupillary size/reactivity, motor/sensory evaluation of extremities, and seizure activity from infusion to discharge. Grade 3-5 CNS event as defined in the NCI CTCAE v3.0 occurring within 12 hours of cellular product infusion will trigger the stopping rules. Other changes temporally related to hUCB infusion (those events occurring within 12 hours of infusion) will be considered associated with the protocol and recorded as an adverse event.
Secondary Outcome Measures
EEG
History including current seizure frequency and anticonvulsant regimen. Comparison of current EEG findings to prior studies.
Fine and Gross Motor
History and physical exam findings compared to previous evaluation. SSEP testing compared to prior tests. MACS and GMFCS classification compared to prior evaluations.
Language
Language will be evaluated before treatment and at follow-up visits 6 months and 1 year. Full evaluations will include measures of language expression, reception, and oral-motor functioning. Formal tests include: The Preschool Language Scale, Fifth Edition (PLS-5), Expressive Vocabulary Test, Second Edition (EVT-2), and Peabody Picture Vocabulary Test, Fourth Edition (PPVT-4). Informal measures include: phonetic inventory, oral motor evaluation and The Rossetti Infant-Toddler Language Scale.
Speech
Speech will be evaluated before treatment and at follow-up visits 6 months and 1 year. Full evaluations will include measures of speech production. Formal tests include: The Comprehensive Assessment of Spoken Language (CASL) and The Arizona Articulation Proficiency Scale- Third Edition.
Bladder: Urodynamics
Questions focusing on toilet training and continence will be included in the patient's history. CMG testing will also be performed, and compared to prior CMG tests.
Full Information
NCT ID
NCT02460484
First Posted
April 23, 2015
Last Updated
March 16, 2022
Sponsor
James Baumgartner, MD
Collaborators
Cord Blood Registry, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02460484
Brief Title
Safety of Autologous Human Umbilical Cord Blood Treatment for Perinatal Arterial Ischemic Stroke
Official Title
Safety of Autologous Human Umbilical Cord Blood Treatment for Perinatal
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Suspended
Why Stopped
Restructuring Cell Lab
Study Start Date
April 2015 (undefined)
Primary Completion Date
June 2022 (Anticipated)
Study Completion Date
June 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
James Baumgartner, MD
Collaborators
Cord Blood Registry, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Autologous human umbilical cord blood (hUCB) stored at Cord Blood Registry will be given to children who have suffered from a Perinatal Arterial Ischemic Stroke. The aim is to determine if hUCB infusion is safe, if late functional outcome is improved, if hUCB treatment improves physiologic response in the child's SSEP & EEG, and the effect of hUCB infusion in altering anatomic findings on MRI.
Detailed Description
Autologous human umbilical cord blood (hUCB) stored at Cord Blood Registry will be given to children who have suffered from a Perinatal Arterial Ischemic Stroke.
Subjects will come to Orlando for pretesting to include an MRI, SSEP, Urodynamics, blood work: CBC, CMP, Hepatic Function Panel, PT/PTT/INR, Chest Xray, EEG, Gross Motor Function Classification, Manual Ability Classification System, and a Speech and Language Evaluation.
After pretesting, the subjects will receive their autologous cord blood infusion intravenously. The subjects will then be monitored for 24 hours post infusion. After 24 hours, the subject will undergo repeat blood work and a chest x ray. Subjects will then be discharged home.
Subjects will follow up in Orlando at 6 months and 1 year post infusion. Follow up testing will repeat the exams performed at pretesting.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Perinatal Arterial Ischemic Stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cord Blood Infusion
Arm Type
Experimental
Arm Description
Autologous cord blood infusion
Intervention Type
Biological
Intervention Name(s)
Autologous Cord Blood Infusion
Intervention Description
Intravenous infusion
Primary Outcome Measure Information:
Title
Composite Outcome: Hemodynamic Safety
Description
Three primary and two secondary hemodynamic indices will be monitored as indices of hemodynamic stability throughout the infusion and post-infusion periods. Heart rate, blood pressure, and oxygen saturation will be recorded every 5 minutes during the infusion, every 30 minutes for 2 hours after infusion and then hourly for 6 hours. A consistent, non-isolated 20% decrease in any of these indices will be prompt additional maneuvers to restore MAP.
Two secondary hemodynamic indices will be monitored as indices of hemodynamic stability: capillary refill and heart rate. Prolongation of capillary refill by 2 seconds from baseline and/or >20% change in heart rate during the procedure will prompt an evaluation as to the etiology of the change in hemodynamic status. An adverse event will be defined as a sustained (> 10 minutes) >20% decrease in MAP. Transient decreases in MAP that respond to fluid infusion or inotropes will not be considered adverse events.
Time Frame
1 year
Title
Composite Outcome: Pulmonary Safety
Description
A concern exists regarding the systemic infusion of leukocytes in a concentrated manner. Theoretically, activated monocytes could function to enhance PMN migration into the lung, as the lung is the primary "first pass" filter for intravenous infusion of any cellular product. PMN mediated organ injury typically occurs over a 6-24 hour time frame. Based on this, Chest radiographs will be performed and evaluated at Baseline and on Post-Infusion Day 1. Chest radiographs will be evaluated for systemic infusion of leukocytes in a concentrated manner. Additionally, blood-oxygen saturation will be monitored by finger oximeter. Moderate respiratory dysfunction within the first 48 hours post infusion will be considered an adverse event but will not warrant stopping the trial unless recommended by the DSMB. In the event of pulmonary dysfunction, standard supportive therapy will be given. Pulmonary symptoms/events corresponding to the CTCAE v3.0 Grade 3 will trigger the stopping rules.
Time Frame
1 year
Title
Composite Outcome: Renal Safety
Description
To minimize the effect of DSMO, our hUCB product will be washed according to Standard Operating Procedures prior to infusion. Though unlikely, it is possible that some quantity of DMSO will remain which could cause toxicity. Renal function/events corresponding to the CTCAE v3.0 Grade 3 will trigger the stopping rules
Time Frame
1 year
Title
Composite Outcome: Neurological Safety
Description
The patient's acute neurologic status will be monitored until discharged. Data recorded every 4 hours includes GCS, pupillary size/reactivity, motor/sensory evaluation of extremities, and seizure activity from infusion to discharge. Grade 3-5 CNS event as defined in the NCI CTCAE v3.0 occurring within 12 hours of cellular product infusion will trigger the stopping rules. Other changes temporally related to hUCB infusion (those events occurring within 12 hours of infusion) will be considered associated with the protocol and recorded as an adverse event.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
EEG
Description
History including current seizure frequency and anticonvulsant regimen. Comparison of current EEG findings to prior studies.
Time Frame
1 year
Title
Fine and Gross Motor
Description
History and physical exam findings compared to previous evaluation. SSEP testing compared to prior tests. MACS and GMFCS classification compared to prior evaluations.
Time Frame
1 year
Title
Language
Description
Language will be evaluated before treatment and at follow-up visits 6 months and 1 year. Full evaluations will include measures of language expression, reception, and oral-motor functioning. Formal tests include: The Preschool Language Scale, Fifth Edition (PLS-5), Expressive Vocabulary Test, Second Edition (EVT-2), and Peabody Picture Vocabulary Test, Fourth Edition (PPVT-4). Informal measures include: phonetic inventory, oral motor evaluation and The Rossetti Infant-Toddler Language Scale.
Time Frame
1 year
Title
Speech
Description
Speech will be evaluated before treatment and at follow-up visits 6 months and 1 year. Full evaluations will include measures of speech production. Formal tests include: The Comprehensive Assessment of Spoken Language (CASL) and The Arizona Articulation Proficiency Scale- Third Edition.
Time Frame
1 year
Title
Bladder: Urodynamics
Description
Questions focusing on toilet training and continence will be included in the patient's history. CMG testing will also be performed, and compared to prior CMG tests.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Weeks
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Between 6 weeks and 6 years of age on the day of study cord blood infusion.
MRI documented single arterial distribution infarction.
Initial injury occurring in the prenatal or perinatal period
Ability of child and caregiver to travel to Orlando, and stay for at least 4 days, and to return for all Follow-up visits (patient is responsible for cost of travel and lodging while in Orlando)
Exclusion Criteria:
Inability to obtain all pertinent medical records, including pertinent physician notes, laboratory findings, and radiographic images, related to the original injury, hospitalization and rehabilitation - must be sent to FHFC research team 14 days prior to scheduled study cord blood treatment. Need brain MRI with flair sequence <2 weeks old.
Recent radiographic evidence (imaging performed within past 2 weeks) of extensive stroke as evidenced by >100ml lesion
Multifocal infarctions on screening MRI.
Evidence of hypoxic-ischemic encephalopathy on screening MRI.
Uncorrected coagulopathy during the baseline period defined as INR > 1.4; PTT> 35 sec; PLT < 100,000
Known history of:
Recently diagnosed infection (within past 2 weeks) requiring treatment and/or medical intervention
Renal disease or altered renal function as defined by serum creatinine >1.5 mg/dL at admission
Hepatic disease or altered liver function as defined by SGPT > 150 U/L, and/or T. Bilirubin >1.3 mg/dL at enrollment
Malignancy
Immunosuppression as defined by WBC < 3 (10x3) at admission
HIV
Any evidence of active maternal infection during the pregnancy (Hepatitis A, Hepatitis B, Hepatitis C, HIV 1, HIV 2, Human T-lymphotropic Virus (HTLV) 1, HTLV 2
Pneumonia, or chronic lung disease requiring oxygen
Cord blood sample contamination
Participation in a concurrent intervention study
Desire for organ-donation in the event of death
Unwillingness or inability to stay for at least four days following cord blood infusion (should any problems arise following the infusion) and to return for 6 month, and 1 year follow-up visits
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Baumgartner, MD
Organizational Affiliation
AdventHealth
Official's Role
Principal Investigator
Facility Information:
Facility Name
Florida Hospital for Children
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Safety of Autologous Human Umbilical Cord Blood Treatment for Perinatal Arterial Ischemic Stroke
We'll reach out to this number within 24 hrs