Ischemic Stroke
Conditions
Brief summary
The purpose of this research study is to find out if bone marrow treatment (bone marrow aspiration and infusion of stem cells) can be safely used in adults who have recently (within 24-72 hours)suffered an acute ischemic stroke.
Detailed description
Our primary hypothesis is that autologous bone marrow mononuclear cell transplantation by intravenous administration is feasible and safe after acute ischemic stroke. Our secondary hypothesis is that autologous transplantation is associated with improved outcome after acute stroke.
Interventions
BIOLOGICALAutologous Bone Marrow Mononuclear Cells
Harvest of bone marrow from ischemic stroke patients, isolation of bone marrow mono-nuclear cells, and peripheral IV infusion of autologous bone marrow mono-nuclear cells
Sponsors
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The University of Texas Health Science Center, Houston
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 83 Years
Healthy volunteers
No
Inclusion criteria
1. acute ischemic stroke 2. age 18 to 83 years If \>80 then the pre-stroke mRS needs to be \< 1) 3. Right hemisphere NIHSS 6 -15, left hemisphere NIHSS 6-18 4. known onset time of acute symptoms 5. stem cell transplantation procedure must be performed within 24 to 72 hrs after stroke symptom onset 6. TPA infusion is allowed
Exclusion criteria
1. NIHSS 1a \> 1 2. pre-stroke mRS \> 1 if \> 80 years of age 3. Ischemic stroke in the last 3 months, any vascular territory 4. MI, primary hemorrhagic or traumatic lesion of the brain within the last 3 months or identified on MRI. Small hemorrhagic transformation of the acute infarct is allowed. 5. seizure disorder 6. developmental delay 7. chronic kidney disease defined as baseline creatinine \>1.4 8. hepatic disease or altered liver function as defined by SGPT \>150 U/L and or T. Bilirubin \>1.6 mg/dL at admission 9. pulmonary disease (e.g, COPD with oxygen-requirement at rest or with ambulation, moderate to severe asthma) 10. mechanical heart valve 11. Active malignancy or diagnosis of malignancy within 5 years prior to the start of screening or any history of chemotherapy or radiation affecting the bone marrow. Skin cancers (except for melanoma) are permitted. 12. prior immunosuppression, including chemotherapy administration within last 3 years or current immunosuppression as defined by WBC \<3 x 103 cells/ml 13. known HIV 14. hemoglobin \<10g/dl 15. uncorrected coagulopathy at the time of consent defined as INR \>1.4; PTT\>37 sec, or thrombocytopenia (PLT\<100,000) 16. any hemodynamic instability at the time of consent (e.g, requiring continuous fluid resuscitation or ionotropic support). 17. Hypoxemia (SaO2\<90%) at the time of consent, respiratory distress or persistent hypoxemia defined as SaO2 \<94% for \>30 minutes occurring at any time from hospital admission to time of consent. Intubation alone is not an exclusion. 18. pregnancy or positive b-HCG 19. current participation in any interventional research study 20. unable to return for follow-up visits for clinical evaluation, laboratory studies, or imaging evaluation 21. Multiple anti-platelet medications (Aggrenox is considered a single platelet agent) 22. Unable to undergo MRI or CT scan 23. Any other condition that the investigator feels would pose a significant hazard to the patient if enrolled. 24. Exclude infarct lesion size \>145cc unless the NIHSS 1a remains \< 1 and there is no evidence of infarct expansion or edema formation on any imaging obtained from admission up to the point just prior to infusion. 25. Exclude IA therapy use or if there is a planned or anticipated hemicraniectomy. Diagnostic angiograms are allowed 26. CT and/or Multimodal MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Related Serious Adverse Events (SR-SAE) | 2 Years | Study Related Serious Adverse Events (SAE) as adjudicated by the DSMB - Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Outcome | 90-days | Modified Rankin Scale (mRS) Score. The mRS is a six point (scored: 0 - 5) scale that measures post stroke disability. A seventh category (mRS = 6) is for patients who have died. A higher score indicates greater degree of disability. Patients scoring '5' are bed ridden, where as those scoring '0' are completely symptom free and independent. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Autologous Bone Marrow Mononuclear Cells Harvest of bone marrow from ischemic stroke patients, isolation and purification of mono-nuclear cell fraction from bone marrow, intravenous administration of autologous bone marrow mono-nuclear cells with a targeted dose of 10 million cells / kg. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Autologous Bone Marrow Mononuclear Cells |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 60.7 years STANDARD_DEVIATION 13.3 |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 25 |
| serious Total, serious adverse events | 15 / 25 |
Outcome results
Primary
Study Related Serious Adverse Events (SR-SAE)
Study Related Serious Adverse Events (SAE) as adjudicated by the DSMB - Events
Time frame: 2 Years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autologous Bone Marrow Mononuclear Cells | Study Related Serious Adverse Events (SR-SAE) | 0 Events |
Secondary
Functional Outcome
Modified Rankin Scale (mRS) Score. The mRS is a six point (scored: 0 - 5) scale that measures post stroke disability. A seventh category (mRS = 6) is for patients who have died. A higher score indicates greater degree of disability. Patients scoring '5' are bed ridden, where as those scoring '0' are completely symptom free and independent.
Time frame: 90-days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Autologous Bone Marrow Mononuclear Cells | Functional Outcome | 3 units on a scale |