Phase I Clinical Trial of Autologous Adipose Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Spinal Cord Injuries
- Sponsor
- Mohamad Bydon
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Incidence of acute adverse events
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Mohamad Bydon
Regulatory Sponsor
Mayo Clinic
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
- •SCI must be traumatic, blunt/non-penetrating in nature and not degenerative
- •SCI must be within two weeks and up to 1 year after the event
- •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
- •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
- •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.
Outcomes
Primary Outcomes
Incidence of acute adverse events
Time Frame: up to 4 weeks post treatment
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
Secondary Outcomes
- Incidence of delayed adverse events(48 weeks post treatment)
- Relationship of adverse events to study drug(4 weeks post-treatment)
- Change in Erythrocyte Sedimentation Rate (ESR)(baseline, 4 weeks post-treatment)
- Incidence of serious adverse events (SAE)(48 weeks post-treatment)
- Severity of adverse events(4 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)(baseline, 96 weeks)
- Change in sensory and motor function following completion of treatment as measured by Somatosensory Evoked Potentials (SSEPs)(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.(approximately 96 weeks post-treatment)
- Change in number of red blood cells following treatment(baseline, 4 weeks post-treatment)
- Change in white blood cells with differential following treatment(baseline, 4 weeks post-treatment)
- Change in number of platelets following treatment(baseline, 4 weeks post-treatment)
- Change in Serum C-Reactive Protein (CRP)(baseline, 4 weeks post-treatment)
- Change in Blood Urea Nitrogen (BUN)(baseline, 4 weeks post-treatment)
- Change in sensory and motor function following completion of treatment as measured by motor evoked potentials (MEP)(baseline, 96 weeks post-treatment)
- Change in Sodium(baseline, 4 weeks post-treatment)
- Change in Potassium(baseline, 4 weeks post-treatment)
- Change in Creatinine(baseline, 4 weeks post-treatment)
- Change in Chloride(baseline, 4 weeks post-treatment)
- Change in Aspartate Aminotransferase (AST)(baseline, 4 weeks post-treatment)
- Change in Glucose(baseline, 4 weeks post-treatment)
- Change in Carbon Dioxide(baseline, 4 weeks post-treatment)