Adipose Stem Cells for Traumatic Spinal Cord Injury

Mohamad Bydon10 enrolled

Overview

The purpose of this study is to determine if mesenchymal stem cells (MSC) derived from the fat tissue can be safely administered into the cerebrospinal fluid (CSF) of patients with spinal cord injury. Adipose-derived mesenchymal stem cells (AD-MSCs) have been used in previous research studies at the Mayo Clinic. All subjects enrolled in this study will receive AD-MSC treatment, which is still experimental and is not approved by the U.S. Food and Drug Administration (FDA) for large scale use. However, the FDA has allowed the use of this agent in this research study.

The proposed study is an open label, prospective Phase I safety and feasibility study of the intrathecal injection of autologous culture-expanded AD-MSCs in patients with severe traumatic spinal cord injury (SCI). All subjects will receive the same dosage of stem cells via intrathecal injection. Enrolled subjects will first undergo a minor surgical procedure in which a sample of the patient's adipose tissue will be harvested from a small incision in the patient's abdomen or thigh. The subject's adipose tissue will then be used to derive and culture-expand AD-MSCs for 4-6 weeks. Autologous AD-MSCs will be transplanted through intrathecal injection at the level of L4-5 under fluoroscopic guidance at a single dose of 100 million cells. Patients will be evaluated at set intervals following the injection: day 2, day 3, week 1, week 2, week 4, week 24, weeks 48, week 72 and week 96.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Spinal Cord Injuries Paralysis

Interventions

Autologous, Adipose derived Mesenchymal Stem CellsBIOLOGICAL

The mesenchymal stem cells will be collected and expanded from the subjects adipose tissue.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female aged 18 years and older 1. 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. 2. 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. 2. AIS grade A or B of SCI 3. SCI must be traumatic, blunt/non-penetrating in nature and not degenerative 4. SCI must be within two weeks and up to 1 year after the event 5. 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 6. 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: 1. Pregnant or nursing, or planning on becoming pregnant during the study period 2. AIS grade of SCI other than A or B 3. History of intra-spinal infection 4. History of superficial infection in the index spinal level within 6 months of study 5. Evidence of current superficial infection affecting the index spinal level at the time of enrollment 6. On chronic, immunosuppressive transplant therapy or having a chronic, immunosuppressive state, including use of systemic steroids/corticosteroids 7. Taking anti-rheumatic disease medication (including methotrexate or other antimetabolites) within 3 months prior to study enrollment 8. Ongoing infectious disease, including but not limited to tuberculosis, HIV, hepatitis, and syphilis 9. Fever, defined as temperature above 100.4 F/38.0 Celsius, or mental confusion at baseline 10. 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. 11. 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). 12. 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. 13. History of blood dyscrasia, including but not limited to anemia, thrombocytopenia, and monoclonal gammopathy 14. Participation in a study of an experimental drug or medical device within 3 months of study enrollment 15. Known allergy to local anesthetics of other components of the study drug 16. Any contraindication to MRI scan according to MRI guidelines, or unwillingness to undergo MRI procedures 17. 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 18. Patients with baseline depression, diagnosed by the Beck Depression Inventory Assessment

Locations (1)

Mayo Clinic

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

Incidence of acute adverse events

An adverse event is defined any untoward or undesirable medical occurrence in the form of signs, symptoms, abnormal findings, or diseases that emerge or worsen relative to baseline (i.e., if present upon study entry) during the study regardless of causal relationship to the study drug

Time frame: up to 4 weeks post treatment

Secondary Outcomes

Incidence of delayed adverse events

Time frame: 48 weeks post treatment

Severity of adverse events

The severity of adverse events will be graded into the following categories: mild, moderate, and severe.

Time frame: 4 weeks post-treatment

Relationship 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.

Time frame: 4 weeks post-treatment

Incidence of serious adverse events (SAE)

SAE is defined as adverse events that result in death, life threatening adverse experiences, hospitalization, new or prolonged disability/incapacity.

Time frame: 48 weeks post-treatment

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).

Data from ClinicalTrials.gov

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Time frame: baseline, 96 weeks

Change in sensory and motor function following completion of treatment as measured by motor evoked potentials (MEP)

Motor Evoked Potentials (MEP) are electrical responses recorded either from muscles, or from axons of the descending motor tract, in response to electrical or magnetic stimulation of nervous system structures that govern movement. While there are many different methods for stimulation and recording, the most common approach involves transcranial electrical stimulation of the motor pathway, using subdermal needle electrodes positioned in the scalp above primary motor cortex.

Time frame: baseline, 96 weeks post-treatment

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.

Time frame: baseline, 96 weeks post-treatment

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.

Time frame: approximately 96 weeks post-treatment

Change in number of red blood cells following treatment

Blood will be drawn in order to monitor for markers of systemic inflammation. The normal range of red blood cells varies slightly between laboratories but is generally between 4.2 - 5.9 million cells/cmm. This can also be referred to as the erythrocyte count and can be expressed in international units as 4.2 - 5.9 x 10\^12 cells per liter.