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

• ClinicalTrials.gov Identifier: NCT00859014
• Recruitment Status: Completed
• First Posted: March 10, 2009
• Results First Posted: January 1, 2015
• Last Update Posted: January 1, 2015
• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Sean Savitz, The University of Texas Health Science Center, Houston

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ischemic Stroke	Biological: Autologous Bone Marrow Mononuclear Cells	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety/Feasibility of Autologous Mononuclear Bone Marrow Cells in Stroke Patients
• Study Start Date: January 2009
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: November 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Study Related Serious Adverse Events (SR-SAE) [ Time Frame: 2 Years ]
   Study Related Serious Adverse Events (SAE) as adjudicated by the DSMB - "Events"

Secondary Outcome Measures :

1. Functional Outcome [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Texas

Memorial Hermann Hospital-Medical Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

National Institutes of Health (NIH)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Sean I Savitz, MD; University of Texas Heath Science Center- Houston

More Information

Publications of Results:

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.

Other 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.

• Responsible Party: Sean Savitz, Professor, Neurology, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT00859014
• Other Study ID Numbers: N01-HB-37163-05; R21HD060978 ( U.S. NIH Grant/Contract )
• First Posted: March 10, 2009
• Results First Posted: January 1, 2015
• Last Update Posted: January 1, 2015
• Last Verified: December 2014

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases