Autologous Adipose Derived Mesenchymal Stem Cells for Spinal Cord Injury Patients
Primary Purpose
Spinal Cord Injuries, Paralysis
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Best Medical Management: Occupational and Physical Therapy
Autologous, Adipose Derived Mesenchymal Stem Cells
Sponsored by
About this trial
This is an interventional treatment trial for Spinal Cord Injuries
Eligibility Criteria
Inclusion Criteria:
Male or female aged 18 years and older
- Females of childbearing potential must have a negative pregnancy test prior to receiving the study drug and will agree to use adequate contraception (hormonal/barrier method or abstinence) from the time of screening to a period of 1 year following completion of the drug treatment cycle. Females of childbearing potential are defined as premenopausal and not surgically sterilized, or post-menopausal for fewer than 2 years. If the urine pregnancy test is positive, the study drug will not be administered and the result will be confirmed by a serum pregnancy test. Serum pregnancy tests will be performed at a central clinical laboratory, whereas urine pregnancy tests will be performed by qualified personnel using kit.
- Females becoming pregnant during the study will continue to be monitored for the duration of the study or completion of the pregnancy, whichever is longer. Monitoring will include perinatal and neonatal outcome. Any SAEs associated with pregnancy will be recorded.
- AIS grade A or B of SCI at the time of injury with or without subsequent improvement within 1 year of injury that has progressed to a higher AIS grade with a plateau in functional improvement
- SCI must be traumatic, blunt/non-penetrating in nature and not degenerative
- Full understanding of the requirements of the study and willingness to comply with the treatment plan, including fat harvesting, laboratory tests, diagnostic imaging, complete physical and neurologic examination and follow-up visits and assessments
- Full understanding of the requirements of home exercise program prescribed by physical and occupational therapists.
- Once the nature of the study is fully explained and prior to any study-related procedure is initiated the subject is willing to provide written, informed consent and complete HIPAA documentation
Exclusion Criteria:
- Pregnant or nursing, or planning on becoming pregnant during the study period
- AIS grade of SCI other than A or B at the time of injury
- Non-traumatic SCI
- History of receiving mesenchymal stem cell, gene or exosome therapy for any indications
- History of intra-spinal infection
- History of superficial infection in the index spinal level within 6 months of study
- Evidence of current superficial infection affecting the index spinal level at the time of enrollment
- On chronic, immunosuppressive transplant therapy or having a chronic, immunosuppressive state, including use of systemic steroids/corticosteroids
- Taking anti-rheumatic disease medication (including methotrexate or other antimetabolites) within 3 months prior to study enrollment
- Ongoing infectious disease, including but not limited to tuberculosis, HIV, hepatitis, and syphilis
- Fever, defined as temperature above 100.4 F/38.0 Celsius, or mental confusion at baseline
- Significant improvement between the time of adipose tissue harvest and the time of injection, defined as improvement from AIS grade A or B to AIS grade C or greater.
- Clinically significant cardiovascular (e.g. history of myocardial infarction, congestive heart failure or uncontrolled hypertension > 90 mmHg diastolic and/or 180 mmHg systolic), neurological (e.g. stroke, TIA) renal, hepatic or endocrine disease (e.g. diabetes, osteoporosis).
- History of malignancy including melanoma with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). Any other malignancy will not be allowed.
- History of blood dyscrasia, including but not limited to anemia, thrombocytopenia, and monoclonal gammopathy
- Participation in a study of an experimental drug or medical device within 3 months of study enrollment
- Known allergy to local anesthetics of other components of the study drug
- Any contraindication to MRI scan according to MRI guidelines, or unwillingness to undergo MRI procedures
- History of or current evidence of alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or use of medical marijuana within 30 days of study entry
- Diagnosis of schizophrenia or bipolar disorder
- Patients with baseline depression, diagnosed by the Beck Depression Inventory Assessment
- Currently taking riluzole for treatment of amyotrophic lateral sclerosis (ALS)
Sites / Locations
- Mayo Clinic in RochesterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Treatment Group 1: AD-MSC Injection
Treatment Group 2: Best Medical Management
Arm Description
Patients will receive a single dose of autologous, adipose derived mesenchymal stem cells one time. The cells are isolated from patient's adipose tissue and expanded for intrathecal delivery.
Patients will be observed over six months while attending physical and occupational therapy. After six months, patients will receive a single dose of autologous, adipose derived mesenchymal stem cells one time. The cells are isolated from patient's adipose tissue and expanded for intrathecal delivery.
Outcomes
Primary Outcome Measures
•Change in sensory and motor function following completion of treatment as measured by the American Spinal Injury Association (ASIA) Impairment Scale (AIS)
The ASIA Impairment Scale describes a person's functional impairment (both motor and sensory) as a result of their spinal cord injury. The scale has 5 levels, ranging from A (complete) to E (normal).
Secondary Outcome Measures
Change in sensory and motor function following completion of treatment as measured by Somatosensory Evoked Potentials (SSEPs)
Somatosensory Evoked Potentials (SSEPs) are electrical responses recorded from the nervous system following electrical stimulation of a peripheral nerve. For example, stimulation of the median nerve at the wrist produces electrical activity that travels along the sensory pathway on its way to the brain. This activity can be recorded with electrodes positioned along that pathway.
change in Neurogenic Bladder Symptom Score (NBSS)
Neurogenic Bladder Symptom Score (NBSS) The NBSS was designed as an objective and validated way to assess bladder symptoms in patients with neurogenic bladder dysfunction as a result of spinal cord injury, multiple sclerosis, and spinal bifida. The NBSS consists of 24 questions. The first question classifies patients by bladder management, but does not make up part of the numeric score. The remaining questions address 3 domains: incontinence, storage and voiding, and consequences. The final question is an overall quality of life question. The total score can range from 0 (no symptoms at all) to 74 (maximum symptoms).
change in Neurogenic Bowel Symptom Score
The Adult Neurogenic Bowel Dysfunction Score¹, also known as the Adult NBD score has been designed to help healthcare professionals evaluate the effectiveness of their patient's current bowel management routine by assessing the impact it has on the patient's quality of life. By having your patients answer 10 simple questions, the Adult NBD Score can help identify and quantify severity of bowel dysfunction in the adult patients. The Adult NBD score consists of 10 questions and is a symptom-score where each symptom is weighted based on its impact on quality of life. The scores from each question are added together and a total score is calculated. The maximum score is 47 while minimum is 0. Score Severity of bowel dysfunction 0-6 Very minor 7-9 Minor 10-13 Moderate 14+ Severe
Incidence of abnormal CSF composition
Composition in reference to normal laboratory values.
Number of subjects who develop a new pathologic mass at the spinal cord area of injection or anywhere along the spinal cord.
Patients will undergo Magnetic Resonance Imaging of the spine and the spinal cord with and without contrast.
Correlation of adverse events to study drug
The relationship of adverse events to study drug will be graded into the following categories: probable, possible, unlikely, unrelated.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04520373
Brief Title
Autologous Adipose Derived Mesenchymal Stem Cells for Spinal Cord Injury Patients
Official Title
CELLTOP Part II: A Phase II Clinical Trial of Autologous Adipose Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 25, 2020 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this research study is to investigate the safety and potential therapeutic effects of autologous, culture-expanded, adipose derived mesenchymal stem cell intrathecal injections in the treatment of spinal cord injury.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries, Paralysis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Group 1: AD-MSC Injection
Arm Type
Experimental
Arm Description
Patients will receive a single dose of autologous, adipose derived mesenchymal stem cells one time. The cells are isolated from patient's adipose tissue and expanded for intrathecal delivery.
Arm Title
Treatment Group 2: Best Medical Management
Arm Type
Active Comparator
Arm Description
Patients will be observed over six months while attending physical and occupational therapy. After six months, patients will receive a single dose of autologous, adipose derived mesenchymal stem cells one time. The cells are isolated from patient's adipose tissue and expanded for intrathecal delivery.
Intervention Type
Other
Intervention Name(s)
Best Medical Management: Occupational and Physical Therapy
Intervention Description
Observation while undergoing Occupational and Physical Therapy for 6 months
Intervention Type
Biological
Intervention Name(s)
Autologous, Adipose Derived Mesenchymal Stem Cells
Intervention Description
The mesenchymal stem cells will be collected and expanded from the patients' adipose tissue.
Primary Outcome Measure Information:
Title
•Change in sensory and motor function following completion of treatment as measured by the American Spinal Injury Association (ASIA) Impairment Scale (AIS)
Description
The ASIA Impairment Scale describes a person's functional impairment (both motor and sensory) as a result of their spinal cord injury. The scale has 5 levels, ranging from A (complete) to E (normal).
Time Frame
up to 12 months post injection
Secondary Outcome Measure Information:
Title
Change in sensory and motor function following completion of treatment as measured by Somatosensory Evoked Potentials (SSEPs)
Description
Somatosensory Evoked Potentials (SSEPs) are electrical responses recorded from the nervous system following electrical stimulation of a peripheral nerve. For example, stimulation of the median nerve at the wrist produces electrical activity that travels along the sensory pathway on its way to the brain. This activity can be recorded with electrodes positioned along that pathway.
Time Frame
baseline, up to 12 months post injection
Title
change in Neurogenic Bladder Symptom Score (NBSS)
Description
Neurogenic Bladder Symptom Score (NBSS) The NBSS was designed as an objective and validated way to assess bladder symptoms in patients with neurogenic bladder dysfunction as a result of spinal cord injury, multiple sclerosis, and spinal bifida. The NBSS consists of 24 questions. The first question classifies patients by bladder management, but does not make up part of the numeric score. The remaining questions address 3 domains: incontinence, storage and voiding, and consequences. The final question is an overall quality of life question. The total score can range from 0 (no symptoms at all) to 74 (maximum symptoms).
Time Frame
up to 24 months post injection
Title
change in Neurogenic Bowel Symptom Score
Description
The Adult Neurogenic Bowel Dysfunction Score¹, also known as the Adult NBD score has been designed to help healthcare professionals evaluate the effectiveness of their patient's current bowel management routine by assessing the impact it has on the patient's quality of life. By having your patients answer 10 simple questions, the Adult NBD Score can help identify and quantify severity of bowel dysfunction in the adult patients. The Adult NBD score consists of 10 questions and is a symptom-score where each symptom is weighted based on its impact on quality of life. The scores from each question are added together and a total score is calculated. The maximum score is 47 while minimum is 0. Score Severity of bowel dysfunction 0-6 Very minor 7-9 Minor 10-13 Moderate 14+ Severe
Time Frame
up to 24 months post injection
Title
Incidence of abnormal CSF composition
Description
Composition in reference to normal laboratory values.
Time Frame
up to 4 weeks post injection
Title
Number of subjects who develop a new pathologic mass at the spinal cord area of injection or anywhere along the spinal cord.
Description
Patients will undergo Magnetic Resonance Imaging of the spine and the spinal cord with and without contrast.
Time Frame
up to 12 months post injection
Title
Correlation of adverse events to study drug
Description
The relationship of adverse events to study drug will be graded into the following categories: probable, possible, unlikely, unrelated.
Time Frame
up to 4 weeks post injection
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female aged 18 years and older
Females of childbearing potential must have a negative pregnancy test prior to receiving the study drug and will agree to use adequate contraception (hormonal/barrier method or abstinence) from the time of screening to a period of 1 year following completion of the drug treatment cycle. Females of childbearing potential are defined as premenopausal and not surgically sterilized, or post-menopausal for fewer than 2 years. If the urine pregnancy test is positive, the study drug will not be administered and the result will be confirmed by a serum pregnancy test. Serum pregnancy tests will be performed at a central clinical laboratory, whereas urine pregnancy tests will be performed by qualified personnel using kit.
Females becoming pregnant during the study will continue to be monitored for the duration of the study or completion of the pregnancy, whichever is longer. Monitoring will include perinatal and neonatal outcome. Any SAEs associated with pregnancy will be recorded.
AIS grade A or B of SCI at the time of injury with or without subsequent improvement within 1 year of injury that has progressed to a higher AIS grade with a plateau in functional improvement
SCI must be traumatic, blunt/non-penetrating in nature and not degenerative
Full understanding of the requirements of the study and willingness to comply with the treatment plan, including fat harvesting, laboratory tests, diagnostic imaging, complete physical and neurologic examination and follow-up visits and assessments
Full understanding of the requirements of home exercise program prescribed by physical and occupational therapists.
Once the nature of the study is fully explained and prior to any study-related procedure is initiated the subject is willing to provide written, informed consent and complete HIPAA documentation
Exclusion Criteria:
Pregnant or nursing, or planning on becoming pregnant during the study period
AIS grade of SCI other than A or B at the time of injury
Non-traumatic SCI
History of receiving mesenchymal stem cell, gene or exosome therapy for any indications
History of intra-spinal infection
History of superficial infection in the index spinal level within 6 months of study
Evidence of current superficial infection affecting the index spinal level at the time of enrollment
On chronic, immunosuppressive transplant therapy or having a chronic, immunosuppressive state, including use of systemic steroids/corticosteroids
Taking anti-rheumatic disease medication (including methotrexate or other antimetabolites) within 3 months prior to study enrollment
Ongoing infectious disease, including but not limited to tuberculosis, HIV, hepatitis, and syphilis
Fever, defined as temperature above 100.4 F/38.0 Celsius, or mental confusion at baseline
Significant improvement between the time of adipose tissue harvest and the time of injection, defined as improvement from AIS grade A or B to AIS grade C or greater.
Clinically significant cardiovascular (e.g. history of myocardial infarction, congestive heart failure or uncontrolled hypertension > 90 mmHg diastolic and/or 180 mmHg systolic), neurological (e.g. stroke, TIA) renal, hepatic or endocrine disease (e.g. diabetes, osteoporosis).
History of malignancy including melanoma with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). Any other malignancy will not be allowed.
History of blood dyscrasia, including but not limited to anemia, thrombocytopenia, and monoclonal gammopathy
Participation in a study of an experimental drug or medical device within 3 months of study enrollment
Known allergy to local anesthetics of other components of the study drug
Any contraindication to MRI scan according to MRI guidelines, or unwillingness to undergo MRI procedures
History of or current evidence of alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or use of medical marijuana within 30 days of study entry
Diagnosis of schizophrenia or bipolar disorder
Patients with baseline depression, diagnosed by the Beck Depression Inventory Assessment
Currently taking riluzole for treatment of amyotrophic lateral sclerosis (ALS)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohamad Bydon, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Osha Grant
Phone
507-293-7992
Email
neuroinformatics@mayo.edu
First Name & Middle Initial & Last Name & Degree
Mohamad Bydon, MD
First Name & Middle Initial & Last Name & Degree
Wenchun Qu, MD, PhD
First Name & Middle Initial & Last Name & Degree
Christine Hunt, D.O.
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Autologous Adipose Derived Mesenchymal Stem Cells for Spinal Cord Injury Patients
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