Percutaneous Image Guided Delivery of Autologous Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Symptomatic Degenerated Intervertebral Disc Disease
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Rate of treatment related adverse events
研究概览
简要总结
This study seeks to bridge these technologies and obtain data regarding the safety and efficacy of image guided percutaneous needle injection of expanded autologous bone marrow derived mesenchymal stem cells to symptomatic degenerated intervertebral discs in humans. The primary outcome will be to assess the safety and efficacy and monitor for adverse events.
详细描述
Bone Marrow Aspiration and Cell Culture Procedure
Utilizing fluoroscopic guidance, a coaxial needle will be advanced to the bone marrow space. The inner portion will be removed and 10-20mL of marrow aspirated.
MSCs will be isolated and cultured in the Case Western Reserve University National Center for Regenerative Medicine/Seidman Cancer Center Cellular Therapy Lab using standard operating procedures established under the ongoing IND - as above.
MSC Delivery/Transplantation Procedure
Utilizing fluoroscopic guidance, a needle will be advanced to the outer annulus of the affected disc(s). Through the coaxial anchor, a needle will be advanced to the middle 1/3 of the disc, and confirmed in two planes (AP and lateral).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Symptoms despite conservative (non-surgical) management for > 6 months
- •Leg pain, if present, is of nonradicular origin, i.e., not due to stimulation of nerve roots or dorsal root ganglion of a spinal nerve by compressive forces.
- •Leg pain, if present, does not extend below the knee and is no greater than 50% of low back pain as measured on a visual analog scale. If bilateral leg pain existed, the worst leg pain is no greater than 50% of low back pain.
- •Diagnostic medical branch block or facet joint injection between 18 months and 2 weeks prior to the study procedure indicates no facet joint involvement.
- •Distress and risk assessment method stratification to a) normal or b) at risk designations
- •Modified Pfirrmann MR classification of implicated intervertebral discs of III, IV, or V
- •Absence of infection
- •Absence of coagulopathy
- •Ability to provide informed written consent
排除标准
- •Age > 80y or < 18 y
- •Neoplasia
- •History of recent or active malignancy(non-melanoma skin cancers, carcinoma in situ, etc. are allowable)
- •Active infection
- •Underlying congenital segmentation or other spinal anomalies that result in differential intervertebral disc pressures
- •Significant spinal stenosis
- •Interpreted as "severe" on any cross sectional imaging study
- •Pregnant or planning to become pregnant
- •Contraindication to MRI
- •Indwelling medical devices such as pacemakers, aneurysm clips, etc
- •Indwelling metal from any other cause (trauma, etc)
- •To be excluded with history and radiographs, as necessary
- •Immunosuppression
- •History or laboratory results indicative of any significant cardiac, endocrine, hematologic, hepatic, immunologic, infectious, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neoplastic, or other disorder that in the opinion of the Principal Investigator or his/her designee would preclude the safe performance of BM aspiration, transplantation of autologous MSCs, or performance of any of the planned study assessments.
- •Uncorrectable coagulopathies
- •Concurrent participation in another investigational trial involving systemic administration of agents or within the previous 30 days.
- •Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index (BMI >35).
- •Clinically relevant instability on flexion-extension as determined by the investigator by overlaying films.
- •Have undergone a previous surgery at the involved level that may have altered the target disc (e.g. discectomy, laminectomy, foraminotomy, fusion, intradiscal electrothermal therapy, intradiscal radiofrequency thermocoagulation etc.).
- •Have an acute fracture of the spine at the time of enrollment in the study. Clinically compromised vertebral bodies at the affected level due to current or past trauma, e.g., sustained pathological fracture or multiple fractures of vertebrae.
- •Have a history of epidural steroid injections within 1 week prior to study treatment.
- •Have received chronic (more than 7 consecutive days) treatment with systemic corticosteroids at a dose equivalent to prednisone ≥ 10 mg/day within 14 days prior to injection procedure.
- •Have received systemic or local nonsteroidal anti-inflammatory drugs (NSAIDS) injections into the index and/or adjacent vertebral levels within 48 hours prior to study procedure.
- •Have a known history of hypersensitivity or anaphylactic reaction to murine or bovine products or dimethyl sulfoxide (DMSO).
- •Have a known history of hypersensitivity or anaphylactic reaction to products from birds, such as feathers, eggs or poultry.
- •Have a positive screen for human immunodeficiency virus (HIV) by antibodies or nucleic acid test.
- •Have had treatment with any investigational therapy or device within 6 months of study procedure and/or plans to participate in any other allogeneic stem cell/progenitor cell therapy trial during the 3-year follow-up period.
- •Have been a recipient of prior stem cell/progenitor cell therapy or other biological intervention to repair the target intervertebral disc.
- •Are transient or has been treated in the last 6 months before enrollment for alcohol and/or drug abuse in an inpatient substance abuse program.
- •Habitual use of tobacco throughout the trial and follow-up.
- •Have a mental illness that could prevent completion of the study or protocol questionnaires. If subjects with psychiatric disease are stable, then they should be allowed to participate in the trial.
- •Neurological diseases including unstable diseases or disease which renders subjects unable to give informed consent which renders unable to give informed consent. (Subjects with well controlled epilepsy should not be excluded.)
研究组 & 干预措施
MSC treatment group 1
Low dose of Autologous Bone Marrow Derived Mesenchymal Stem Cells (MSC) -A one time injection of 1-2 ml of 2 x 106/ml concentrated solution
干预措施: MSC Treatment group 1 (low dose) (Drug)
MSC treatment group 2
High dose of Autologous Bone Marrow Derived Mesenchymal Stem Cells (MSC) -A one time injection of 1-2 ml of 4 x 106/ml concentrated solution
干预措施: MSC Treatment group 2 (high dose) (Drug)
Healthy Control (no treatment)
Comparative analysis of psychometric and morphometric based data
干预措施: Healthy Control (no treatment) (Other)
结局指标
主要结局
Rate of treatment related adverse events
时间窗: From baseline/randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year.
assessing for worsening of patients' baseline symptoms or functions (will be considered an AE); (also general AE events), particularly AE events related to the procedures/treatment. All AEs will be assessed by common terminology criteria for adverse events. .
次要结局
- Changes in Pain - Oswestry Disability Index (ODI) scores over time(Baseline, 1 month, 6 months and 1 year)
- changes in Quality of life - Short form Health Survey 36 (SF-36)(Baseline, 1 month, 6 months and 1 year)
- Changes in Pain -Visual Analogue Scale (VAS) for back pain(Baseline, 1 month, 6 months and 1 year)
- changes in MRI monitoring of transplant site(Baseline and 1 year, if a subject were to withdraw prior to completion of the study and received MSC an MRI with be obtained.)
研究者
Salim M Hayek
MD, PhD, Chief, Division of Pain Medicine
University Hospitals Cleveland Medical Center