Phase I Clinical Trial of Autologous Adipose Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Incidence of acute adverse events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •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
- •Patients with baseline depression, diagnosed by the Beck Depression Inventory Assessment
结局指标
主要结局
Incidence of acute adverse events
时间窗: 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
次要结局
- 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)
研究者
Mohamad Bydon
Regulatory Sponsor
Mayo Clinic