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

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT00859014
• Collaborator: National Institutes of Health (NIH) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 58
• Patients Per Site Per Month: 0.4

Study Details

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
• 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: Jan 1, 2009
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 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) [2 Years]

   Study Related Serious Adverse Events (SAE) as adjudicated by the DSMB - "Events"

Secondary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 83 Years
• Sexes Eligible for Study: All
• Accepts 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 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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

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
• First Posted: Mar 10, 2009
• Last Update Posted: Jan 1, 2015
• Last Verified: Dec 1, 2014

• Additional relevant MeSH terms: Stroke; Ischemic Stroke

Study Results

Participant Flow

Arm/Group Title	Autologous Bone Marrow Mononuclear Cells
Arm/Group Description	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.
Period Title: Overall Study
STARTED	25
COMPLETED	20
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Autologous Bone Marrow Mononuclear Cells
Arm/Group Description	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.
Overall Participants	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.7 (13.3)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 52%
>=65 years	12 48%
Sex: Female, Male (Count of Participants)
Female	14 56%
Male	11 44%
Region of Enrollment (participants) [Number]
United States	25 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Bone Marrow Mononuclear Cells
Arm/Group Description	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.
Measure Participants	25
Number [Events]	0

2. Secondary Outcome

Title	Functional Outcome
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Bone Marrow Mononuclear Cells
Arm/Group Description	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.
Measure Participants	25
Median (Inter-Quartile Range) [units on a scale]	3

Adverse Events

Time Frame	2 Years
Arm/Group Title	Autologous Bone Marrow Mononuclear Cells
Arm/Group Description	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.
All Cause Mortality
	Autologous Bone Marrow Mononuclear Cells
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Autologous Bone Marrow Mononuclear Cells
	Affected / at Risk (%)	# Events
Total	15/25 (60%)
Cardiac disorders
Myocardial Infarction	1/25 (4%)
Congestive Heart Failure	1/25 (4%)
Bradycardia	1/25 (4%)
General disorders
Numbness	1/25 (4%)
Hospital admission for observation	1/25 (4%)
Infections and infestations
Sepsis	1/25 (4%)
Musculoskeletal and connective tissue disorders
Fracture Lumbar Vertebra	1/25 (4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Primary Non Small Cell Lung Carcinoma	1/25 (4%)
Nervous system disorders
Ischemic Stroke	2/25 (8%)
Stroke Expansion	3/25 (12%)
Syncope	2/25 (8%)
Seizure	2/25 (8%)
Carotid Hyperperfusion Syndrome	1/25 (4%)
Renal and urinary disorders
Renal Failure	3/25 (12%)
Urinary Tract Infection	1/25 (4%)
Pyelonephritis	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Edema	1/25 (4%)
Vascular disorders
Hypotension	1/25 (4%)
Hypertension	1/25 (4%)
Other (Not Including Serious) Adverse Events
	Autologous Bone Marrow Mononuclear Cells
	Affected / at Risk (%)	# Events
Total	24/25 (96%)
Blood and lymphatic system disorders
Anemia	5/25 (20%)
Leukocytopenia	3/25 (12%)
Prolonged Partial Thromboplastin Time	3/25 (12%)
Decreased Hemoglobin	14/25 (56%)
Gastrointestinal disorders
Colitis	2/25 (8%)
General disorders
Nausea	2/25 (8%)
Vomitting	2/25 (8%)
Culture Bottle Skin Contamination, Suspected	5/25 (20%)
Fall	2/25 (8%)
Headache	2/25 (8%)
Decubitus Ulcer	3/25 (12%)
Peripheral Edema	3/25 (12%)
Infections and infestations
Urinary Tract Infection	10/25 (40%)
Investigations
Increased Alanine Aminotransferase	7/25 (28%)
Increased Aspartate Aminotransferase	11/25 (44%)
Increased INR	5/25 (20%)
Increased Lipase	2/25 (8%)
Hyperglycemia	6/25 (24%)
Hypernatremia	3/25 (12%)
Hypoalbuminemia	4/25 (16%)
Hypocalcemia	7/25 (28%)
Hypokalemia	3/25 (12%)
Hyponatremia	4/25 (16%)
Hypophosphatemia	3/25 (12%)
Musculoskeletal and connective tissue disorders
Pain	9/25 (36%)
Nervous system disorders
Hemorrhagic Transformation of Ischemic Stroke	7/25 (28%)
Ischemic Stroke	2/25 (8%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	3/25 (12%)
Atelectasis	5/25 (20%)
Vascular disorders
Hypotension	5/25 (20%)

Limitations/Caveats

This is a Phase I safety and feasibility study, designed without a control group. Small sample size and inclusion of selected patients warrants caution in interpretation of findings. A randomized controlled study is needed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.