Safety/Feasibility of Autologous Mononuclear Bone Marrow Cells in Stroke Patients

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke
• Intervention / Treatment: Biological: Autologous Bone Marrow Mononuclear Cells

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital-Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 exclusion criteria will be:

    • hemispheric strokes < 1.5 cm maximum diameter (on the MRI as seen on the diffusion-weighted imaging or CT)
    • midline shift >1mm or significant hemorrhagic transformation of the acute infarct

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Autologous 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study Related Serious Adverse Events (SR-SAE)	Study Related Serious Adverse Events (SAE) as adjudicated by the DSMB - "Events"	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	90-days

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Sean I Savitz, MD, University of Texas Heath Science Center- Houston

Publications and helpful links

General Publications

• Vahidy FS, Alderman S, Savitz SI. Challenges enrolling patients with acute ischemic stroke into cell therapy trials. Stem Cells Dev. 2013 Jan 1;22(1):27-30. doi: 10.1089/scd.2012.0404. Epub 2012 Oct 15.
• Savitz SI, Misra V, Kasam M, Juneja H, Cox CS Jr, Alderman S, Aisiku I, Kar S, Gee A, Grotta JC. Intravenous autologous bone marrow mononuclear cells for ischemic stroke. Ann Neurol. 2011 Jul;70(1):59-69. doi: 10.1002/ana.22458.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 9, 2009
• First Posted (Estimate): March 10, 2009

Study Record Updates

• Last Update Posted (Estimate): January 1, 2015
• Last Update Submitted That Met QC Criteria: December 31, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: N01-HB-37163-05; R21HD060978 (U.S. NIH Grant/Contract)