Phase III Study of Human Bone Marrow-Derived Mesenchymal Stem Cells to Treat AS
试验速览
- 阶段
- 2 期
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- The Assessment of Spondyloarthritis International Society (ASAS)20 response
研究概览
简要总结
The purpose of this study is to evaluate the safety and clinical effect of mesenchymal stem cells (MSCs) derived from human bone marrow at a dose of 1.0E+6 MSC/kg in subject for the therapy of Ankylosing spondylitis (AS) and to compare the efficacy of MSCs and Etanercept to treat this disease.
详细描述
Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease involving primarily the sacroiliac joints and the axial skeleton. The main clinical features are back pain and progressive stiffness of the spine. Oligoarthritis of the hips and shoulders, enthesopathy, and anterior uveitis are common, and involvement of the heart and lungs is rare. The current understanding of the pathogenesis of this disorder is limited.It mainly about to hereditary susceptibility (eg HLA-B27),infection and autoimmunity.
Although traditional drugs, such as Nonsteroidal antiinflammatory drugs (NSAIDs) disease-modifying antirheumatic drugs (DMARDs such as methotrexate, salicylazosulfapyridine OR thalidomide) and steroids have been used in the treatment of AS, however, many studies have indicated that the overall response to these drugs is not satisfied. Addition, the severe side effects of these drugs have also been observed. The management of AS patients therefore remains unsatisfactory and targeted therapies are needed. Although the application of TNF alpha receptor inhibitor (such as Etanercept) has got the success in the early treatment of ankylosing spondylitis, the tolerance to this biological agent make the therapy to this disease rather difficult. Recently, owning to its immunoregulatory, immunosuppressive, stimulating hematopoiesis and tissue repairing properties, the infusion of human MSCs isolated from human bone marrow have been a promising and effective treatment to AS patients. This study will evaluate the safety and effectiveness of MSC transplantation in the AS patients and compare the efficiency with the Etanercept to treat AS patients.
This study will last 2 to 3 years. Participants will be randomly assigned to receive either MSC transplant therapy (experimental group) or Etanercept therapy (control group). Patients will undergo MSC transplant at the start of the study on Day 0. The experimental group will receive infusion per week in the first 4 weeks and every two weeks in the second 8 weeks, totally for 12 weeks. After 3 months, patients will receive the second MSC transplantation. After 12 weeks (Phase I) and 48 weeks (Phase II) from the first transplantation, patients will be evaluated.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The male or female patient aged 18 to 45 years;
- •Fulfill 1984 modified NewYork classification criteria for AS;
- •The score of the Bath AS Disease Activity Index (BASDAI)≥40 on (0-100) despite optimal non-steroidal anti-inflammatory drug (NSAID) treatment.
- •Before each experiment, patients subscribe voluntarily to the agreement approved by Ethics Committees and sign the date.
排除标准
- •The patient diagnosed in doubt;
- •Completely stiff spine
- •Received spinal or joint surgery within 2 months
- •Received anti-TNF therapy within 3 months
- •pregnant or suckling period female patients;
- •Patients with the Medical or mentally imbalance charged by researchers. patients associated cardiovascular, cerebrovascular, liver,renal and hematological system diseases or mental disease;
- •Patients could not accept the research or could not cooperate well. Patients with other sever diseases at the same time, such as abnormality of joints, other seronegative spondyloarthropathy, or other Rheumatic Diseases.
研究组 & 干预措施
Intravenous infusion of MSCs
Human bone marrow-derived MSCs at a dose of 1.0E+6 MSC/kg, receive infusion per week in the first 4 weeks and every two weeks in the second 8 weeks. total for 12 weeks.
干预措施: Intravenous infusion of MSCs (Biological)
Etanercept
50mg,hypodermic injection,once per week, for 12 weeks
干预措施: Etanercept (Drug)
结局指标
主要结局
The Assessment of Spondyloarthritis International Society (ASAS)20 response
时间窗: 48 weeks
ASAS measures symptomatic improvement in AS patients.ASAS=4 domains:patient global assessment of disease activity,pain,function,inflammation.ASAS 20=20% improvement(vs.baseline)and an absolute change≥1 units on a 0-10 scale(0=no disease activity;10=high disease activity)for ≥3 domains,and no worsening in remaining domain.
次要结局
- BASDAI score comparing to baseline(48 weeks)
- BASFI score comparing to baseline(48 weeks)
- Imageology(48 weeks)
- C-reactive protein (CRP)(12 weeks)
- Erythrocyte sedimentation rate (ESR)(12 weeks)
- Tumor necrosis factor alpha (TNF-α)(12 weeks)
- Interleukin 6 (IL-6)(12 weeks)
- Interleukin 17 (IL-17)(12 weeks)
研究者
Shen Huiyong
Director of Orthopedics, Sun Yat-sen Memorial Hospital
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University