A Study of Modified Stem Cells in Stable Ischemic Stroke

• ClinicalTrials.gov Identifier: NCT01287936
• Recruitment Status: Completed
• First Posted: February 2, 2011
• Results First Posted: February 3, 2023
• Last Update Posted: February 3, 2023
• Sponsor: SanBio, Inc.
• Information provided by (Responsible Party): SanBio, Inc.

Study Description

Brief Summary:

The primary purpose of the clinical study is to determine the safety of a modified stem cell SB623 when administered to chronic, stable ischemic stroke patients. A second purpose is to determine whether SB623 might improve stroke symptoms. Chronic, stable ischemic stroke patients must be between 6 and 60 months after their stroke, and with only this one prior stroke, and with no further improvement from physical therapy.

Condition or disease	Intervention/treatment	Phase
Chronic Ischemic Stroke	Biological: SB623	Phase 1; Phase 2

Detailed Description:

Chronic, stable stroke patients have no existing alternative treatments after rehabilitation therapy. SB623, a modified stem cell preparation, has been shown to improve motor function when administered in animal models of stable stroke. Safety studies in animals have shown no adverse events attributed to SB623. Patients who meet the entry criteria for this study will have regular examinations, radiological evaluations (CT, MRI, PET), and be followed for two years. Regular neurological evaluations will also be done using standard questionnaires, with occasional video recording if improvements are evident. Key entry criteria for this study, in addition to 6-60 months post-ischemic stroke, include moderately severe symptoms--e.g., difficulty standing or walking, and/or difficulty using arms or hands, and/or speech impediments.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2A Study of the Safety and Efficacy of Modified Stromal Cells (SB623) in Patients With Stable Ischemic Stroke
• Study Start Date: January 2011
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: SB623 Implant (2.5M); 2.5 million SB623 cells	Biological: SB623; SB623, a modified stem-cell product
Experimental: SB623 Implant (5.0M); 5 million SB623 cells	Biological: SB623; SB623, a modified stem-cell product
Experimental: SB623 Implant (10.0M); 10 million SB623 cells	Biological: SB623; SB623, a modified stem-cell product

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 6 months ]

   Number of subjects with TEAEs by maximum severity. The severity of all AEs was assessed by the Investigator using the World Health Organization (WHO) Toxicity Scale. For abnormalities not found elsewhere in the WHO table, the following scale was used to assign severity:

   Mild: Transient mild discomfort; no limitation in activity; no medical intervention/therapy required.

   Moderate: Mild-to-moderate limitation in activity; some assistance may be need. No or minimal medical intervention/therapy required.

   Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required; hospitalization or prolongation of current hospitalization possible.

   Life-threatening: Extreme limitation in activity, significant assistance required; significant medial intervention/therapy required; hospitalization or prolongation of current hospitalization or hospice care probable.

Secondary Outcome Measures :

1. Change in the European Stroke Scale (ESS) Total Score From Baseline at Month 6 [ Time Frame: 6 months ]
   The ESS is the sum of 14 items that are used to assess a patient who has recently had a stroke. These 14 items are level of consciousness, comprehension, speech, visual field, gaze, facial movement, arm in outstretched position, arm raising, extension of the wrist, fingers, leg maintained in position, leg flexing, dorsiflexion of the foot, and gait. A certain number of points are given for each parameter. The range of the total score of ESS is 0 - 100, with a completely normal person having a score of 100 and maximally affected person with a score of zero.
2. Change in the European Stroke Scale (ESS) Motor Function Total Score From Baseline at Month 6 [ Time Frame: 6 months ]
   The ESS motor function score is a sum of the selected items: facial movement, arm in outstretched position, arm raising, extension of wrist, fingers, leg maintained in position, leg flexing, dorsiflexion of foot, and gait. A completely normal person will have a score of 66. The maximally affected person will have a score of zero.
3. Change in the National Institutes of Health Stroke Scale (NIHSS) Total Score From Baseline at Month 6 [ Time Frame: 6 months ]
   The NIHSS is a standardized method used to measure the level of impairment caused by a stroke. The scale consists of 11 items that measure several aspects of brain function, including consciousness, vision, sensation, movement, speech, and language. A certain number of points are given for each impairment uncovered during a focused neurological examination. A maximal score of 42 represents the most severe and devastating stroke with 0=no stroke, 1-4=minor stroke, 5-15=moderate stroke, 15-20=moderate/severe stroke, and 21-42=severe stroke.
4. Change in the National Institutes of Health Stroke Scale (NIHSS) Motor Function Total Score From Baseline at Month 6 [ Time Frame: 6 months ]
   The NIHSS is a standardized method used to measure the level of impairment caused by a stroke. The NIHSS Motor Function Total Score consists of 3 items: motor arm, motor leg, and limb ataxia, with 0 = no stroke and a maximal score of 18 = most severe impairment for motor function.
5. Change in the Modified Rankin Scale (mRS) Response From Baseline at Month 6 [ Time Frame: 6 months ]
   The mRS is a commonly used scale for measuring the degree of disability in daily activities for patients who have suffered a stroke. The mRS is an ordinal scale from 0 (no symptoms at all) to 5 (severe disability; requiring constant nursing care and attention, bedridden, incontinent) with a sixth category of death.
6. Change in the Fugl-Meyer Total Score From Baseline at Month 6 [ Time Frame: 6 months ]
   The Fugl-Meyer Scale is a stroke-specific, performance-based impairment index. The scale is comprised of 5 domains (motor score, sensation, balance, joint range of motion, and joint pain) with 155 items in total. Scoring is based on direct observation of performance. Scale items in all 5 domains are scored on the basis of ability to complete the item using a 3-point Likert-type ordinal scale, where 0=cannot perform, 1=performs partially, and 2=performs fully. Points are divided among the domains: (a) Motor performance [0 (hemiplegia) - 100 (normal motor performance) points]; (b) Balance [0-14 points: 6 for sitting; 8 for standing]; (c) Sensation [0-24 points: 8 for light touch; 16 for position sense]; (d) Joint range of motion [0-44 points]; (e) Joint pain [0-44 points]. For all domains, a maximally affected person will score 0 while a fully functional person will have the highest score. All items are summed to provide a minimum score of 0 and a maximum score of 226.
7. Change in the Fugl-Meyer Motor Total Score (FMMS) Total Score From Baseline at Month 6 [ Time Frame: 6 months ]
   The FMMS is used as a clinical measure of body function impairment after stroke that assesses several dimensions of motor impairment, including range of motion in upper and lower limbs, reflex activity, volitional movement, and coordination. The FMMS motor total score ranged from 0 (hemiplegia) to a maximum of 100 points (normal motor performance), and is comprised of a 33-item upper extremity subscale (UE-FMMS) and the 17-item lower extremity subscale (LE-FMMS). Items were scored on a 3-point ordinal scale: 0= cannot perform; 1= partial motion; 2= full motion Individual items are summed to determine scores for the 2 subscale scores, as well as a motor total score (total of the 2 subscales UE-FMMS and LE-FMMS). As a result, the UE-FMMS subscale score ranged from 0 to 66 and the LE-FMMS subscale score ranged from 0 to 34. A maximally affected person will have a score of 0 while a fully functional person will have the highest score (i.e., 34 for LE-FMMS, 66 for UE-FMMS, 100 for FMMS)
8. Change in the Fugl-Meyer Upper Extremity Motor Function Total Score From Baseline at Month 6 [ Time Frame: 6 months ]
   The Fugl-Meyer Upper Extremity subscale (UE-FMMS) is comprised of 33 items that assess several dimensions of motor impairment, including range of motion in upper limbs, reflex activity, volitional movement, and coordination. Scoring is based on direct observation of performance and is scored using a 3-point ordinal scale, where 0=cannot perform; 1=partial motion; and 2=full motion Individual items are summed to provide ranging from 0 (minimum) to 66 (maximum). A maximally affected person will have a score of 0 while a fully functional person will a score of 66.
9. Change in the Fugl-Meyer Lower Extremity Motor Function Total Score From Baseline at Month 6 [ Time Frame: 6 months ]
   The Fugl-Meyer Lower Extremity subscale (LE-FMMS) is comprised of 17 items that assess several dimensions of motor impairment, including range of motion in lower limbs, reflex activity, volitional movement, and coordination. Scoring is based on direct observation of performance and is scored using a 3-point ordinal scale, where 0=cannot perform; 1=partial motion; and 2=full motion Individual items are summed to provide ranging from 0 (minimum) to 34 (maximum). A maximally affected person will have a score of 0 while a fully functional person will a score of 34.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Documented history of one completed ischemic stroke in subcortical region of MCA or lenticulostriate artery with or without cortical involvement
• Between 6 and 60 months post-stroke, and having a motor neurological deficit
• No significant further improvement with physical therapy/rehabilitation
• Able and willing to undergo computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) scans of the head

Exclusion Criteria:

• History of more than 1 symptomatic stroke
• History of seizures
• History or presence of any other major neurological disease
• Myocardial infarction within prior 6 mos.
• Known presence of any malignancy except squamous or basal cell carcinoma of the skin
• Participation in any other investigational trial within 4 weeks of initial screening and within 7 weeks of study entry
• Contraindications to head CT, MRI, or PET
• Pregnant or lactating

Contacts and Locations

Locations

United States, Alabama

University of Alabama

Birmingham, Alabama, United States, 35294-3410

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States, 60611

United States, Pennsylvania

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

SanBio, Inc.

Investigators

• Principal Investigator: Gary K Steinberg, M.D., Ph.D.; Stanford University
• Principal Investigator: Lawrence R Wechsler, M.D.; University of Pittsburgh Medical Center
• Principal Investigator: Joshua M Rosenow, M.D.,FACS; Northwestern University Feinberg School of Medicine
• Principal Investigator: James Markert, M.D.; University of Alabama at Birmingham
• Principal Investigator: Robert E Gross, M.D., Ph.D.; Emory University

  Study Documents (Full-Text)

Documents provided by SanBio, Inc.:

Study Protocol and Informed Consent Form  [PDF] September 11, 2014

Statistical Analysis Plan  [PDF] December 14, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Steinberg GK, Kondziolka D, Wechsler LR, Lunsford LD, Kim AS, Johnson JN, Bates D, Poggio G, Case C, McGrogan M, Yankee EW, Schwartz NE. Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow-derived mesenchymal stem cells (SB623): a phase 1/2a study. J Neurosurg. 2018 Nov 23:1-11. doi: 10.3171/2018.5.JNS173147. Online ahead of print.

Steinberg GK, Kondziolka D, Wechsler LR, Lunsford LD, Coburn ML, Billigen JB, Kim AS, Johnson JN, Bates D, King B, Case C, McGrogan M, Yankee EW, Schwartz NE. Clinical Outcomes of Transplanted Modified Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study. Stroke. 2016 Jul;47(7):1817-24. doi: 10.1161/STROKEAHA.116.012995. Epub 2016 Jun 2.

• Responsible Party: SanBio, Inc.
• ClinicalTrials.gov Identifier: NCT01287936
• Other Study ID Numbers: SB-STR01
• First Posted: February 2, 2011
• Results First Posted: February 3, 2023
• Last Update Posted: February 3, 2023
• Last Verified: January 2023

Keywords provided by SanBio, Inc.:

Chronic Stroke; Stable Stroke; Ischemic Stroke; Fixed Motor Deficits

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis