Investigation of Neural Stem Cells in Ischemic Stroke
- Conditions
- Ischemic StrokeChronic StrokeHemiparesisArm Paralysis
- Interventions
- Combination Product: CTX0E03 Drug Product and delivery deviceDrug: Placebo
- Registration Number
- NCT03629275
- Lead Sponsor
- ReNeuron Limited
- Brief Summary
A study of stereotactic, intracerebral injection of CTX0E03 neural stem cells into patients with moderate to moderately severe disability as a result of an ischemic stroke.
- Detailed Description
This is a randomized, placebo-controlled, multi-center study. Patients with persistent disability 6-24 months following an ischemic stroke will be enrolled following confirmation of eligibility. Patients will be randomized 2:1 to undergo a stereotactic surgery and receive a single administration of CTX0E03 Drug Product by intracerebral implantation or undergo sham surgery only (placebo). Patients will be followed for 12 months after surgery with follow-up assessments occurring at various time points over the 12 months. All eligible patients will be assigned a standardized Physical Therapy (PT) program. Patients will complete their daily PT exercises at home for 12 weeks after their surgery.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 15
- Ischemic stroke that includes the supratentorial region as confirmed by CT or MRI, occurring within 6 to 24 months of the time that surgical intervention will be performed (Qualifying Stroke Event)
- Modified Rankin Score of 3 or 4 due to the Qualifying Stroke Event
- Some residual upper limb movement
- Sufficient cognitive and language abilities to comprehend verbal commands and to carry out the study assessments
- No medical conditions that would preclude neurosurgery with appropriate preparation and management.
- Ability to attend study visits and complete all study assessments including ability to provide informed consent
- Modified Rankin Score of >1 prior to the Qualifying Stroke Event
- Stroke due to hemorrhage or stroke known or suspected of being caused by, or related to, connective tissue disorder, congenital disorder of the cerebral vessels or a disorder of thrombosis; patients with atrial fibrillation as a suspected cause of stroke are NOT excluded
- Neurosurgical pathway obstructed by vascular malformation or cavity
- History of neurological or other disease resulting in significant functional impairment (e.g. Parkinson's disease, motor neuron disease, moderate dementia, arthritis, contractures or fixed anatomical abnormality)
- Inability to stop or transition off valproic acid or other demethylating agents or Histone deacetylases (HDAC) inhibitors for 1 week before and 4 weeks after surgery
- Use of selective serotonin reuptake inhibitors (SSRI), unless the subject is on a stable dose that has been started at least 2-months before screening (V1)
- Use of antispasticity medications (excluding oral antispasticity medications if they have been taken regularly for at least one month prior to surgery)The use of Botox® or similar is allowed if the last dose was ≥3 months prior to screening; however, its use will be prohibited until following the 12 month visit
- Inability to discontinue anticoagulation therapy for a required interval
- History of malignant disease within the last 5 years, or any history of primary or secondary brain malignant disease
- Patients who have previously participated in a cell-based therapy study at any time or in any other study involving an investigational product or rehabilitation study within the last 30 days
- Patients with clinically significant lab values, including positive Class I human leukocyte antigen (HLA) antibodies specific for CTX0E03
- Planned initiation of any new PT regimen within 6-months of surgery
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CTX0E03 Drug Product and delivery device CTX0E03 Drug Product and delivery device 20 million neural stem cells Placebo Placebo Sham Surgery
- Primary Outcome Measures
Name Time Method Proportion of subjects in which Modified Rankin Scale (mRS) improves by ≥1 point at Month 6 from Baseline 6 months The mRS is an ordinal scale from 0-6, where 0 represents no disability, and each grade above 0 represents a subject's increased level of disability and dependence upon others to perform daily activities.
- Secondary Outcome Measures
Name Time Method Change from baseline in a subject's executive processing speed, language skills and memory using the Symbol Digit Modalities Test. 6 months Validated test assessing different aspects of cognitive function.
Change from baseline in a subject's executive processing speed, language skills and memory using the Multilingual Naming Test. 6 months Validated test assessing different aspects of cognitive function.
Change from baseline in a subject's executive processing speed, language skills and memory using the Montreal Cognitive Assessment. 6 months Validated test assessing different aspects of cognitive function.
Change from baseline in restoring a subject's motor function using the Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA). 6 months The FMA is used to assess motor function in post-stroke, hemiplegic patients. The FMA is comprised of 5 sections, and respective items within each section are scored using a 3-point ordinal scale with 0 representing inability to perform task. Total possible score is 226.
Change from baseline in a subject's ability to execute activities of daily living using the Barthel Index (BI). 6 months The BI is an ordinal scale used to measure a patient's ability to perform activities of daily living. Sum scores from 10 items are calculated with total possible scores ranging from 0-100, with lower scores indicating increased disability.
Change from baseline in a subject's basic mobility and balance using the Timed Up and Go Test (TUG). 6 months TUG is a timed activity assessing mobility and balance in which subjects are asked to stand up from a chair, walk a distance of 3 meters, turn around, walk back to chair and seat themselves. Scores consist of time taken to complete the activity, in seconds.
Change from baseline in a subject's neurological deficits using the National Institute of Health Stroke Scale (NIHSS). 6 months The NIHSS is comprised of 15 items used to assess severity of impairment due to stroke with each item scored on a 3 or 4 point ordinal scale in which 0 represents no impairment. Total sum score range from 0-42: higher score reflects greater severity.
Change from baseline in a subject's perception to stroke recovery using the Stroke Impact Scale (SIS). 6 months The SIS is a stroke-specific, comprehensive measure of health status. The SIS is comprised of 59 items with each item rated on a 5 point Likert scale in terms difficulty. A score of 1 represents an inability to complete an item, where a score of 5 represents no difficulty.
Change from baseline in the function of subject's paretic limb using the Chedoke Arm and Hand Activity Inventory (CAHAI). 6 months The CAHAI is validated to assess paretic limb function and consists of 13 functional tasks, each scored on a 7-point scale, with total test scores obtained by summing each task score. Total scores can range from 13-91 with higher scores indicating greater ability.
Change from baseline in a subject's executive processing speed, language skills and memory using Controlled Oral Word Association tasks. 6 months Validated test assessing different aspects of cognitive function.
Change from baseline in subject's global rating of change regarding their limitations of activity, symptoms, and overall quality of life. 6 months Self-administered 2 factor questionnaire assessing change in limitations of activity, symptoms, and overall quality of life.
Change from baseline in a subject's health-related quality of life using the EQ-5D-5L. 6 months Subjects rate each of 5 dimensions with a numerical rating (1-5) where 1 represents no difficulty to 5 representing an inability, and where a lower total score represents better quality of life.
Safety: To assess the number and severity of adverse events and medical device incidents that occur over the study period. 12 months
Trial Locations
- Locations (22)
Augusta University
🇺🇸Augusta, Georgia, United States
University of California, Irvine
🇺🇸Irvine, California, United States
Emory
🇺🇸Atlanta, Georgia, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Shirley Ryan Ability Lab
🇺🇸Chicago, Illinois, United States
University of California, San Diego
🇺🇸San Diego, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Southern California Neurorestoration Center
🇺🇸Los Angeles, California, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Duke University School of Medicine
🇺🇸Durham, North Carolina, United States
MedStar Health Research Institute
🇺🇸Hyattsville, Maryland, United States
University of Arkansas
🇺🇸Little Rock, Arkansas, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of Miami
🇺🇸Coral Gables, Florida, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
JFK Neuroscience Institute
🇺🇸Edison, New Jersey, United States
Albany Medical College
🇺🇸Albany, New York, United States
Chattanooga Center for Neurologic Research
🇺🇸Chattanooga, Tennessee, United States
University of Texas Health Science Center
🇺🇸San Antonio, Texas, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States