Safety and Efficacy Study of Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes-a Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Exogenous insulin dose
研究概览
简要总结
This is a phase II trial in individuals who have been diagnosed with type 1 diabetes within the previous 6 months. The study is evaluating whether stem cell transplantation is safe when chemotherapy and immunotherapy are used in combination and if it has immune resetting effect that may halt the immune attack to pancreas islets and thus preserve the body's own insulin production.
详细描述
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Generally, at the time someone is diagnosed with type 1 diabetes, not all of a person's beta cells have been destroyed. It's important to preserving the remaining precious beta cells so as to stop the diabetes progression.
The exact mechanism of action of Autologous Hematopoietic Stem Cell Transplantation(AHST) in autoimmune disorders is not fully understood. Preliminary data supported post-AHST immune resetting included an increase in thymus-derived naive T cells, decreased central-memory T cells, increased output of recent thymic emigrants, and recovery of a diverse but distinct T-cell receptor repertoire following AHST. In the patients of type 1 diabetes, decreasing titer of anti-GAD antibody may bring improvement of beta-cell function after intensive immunosuppression. Furthermore, there may exit the possibility of regeneration of beta cells from surviving beta cells or from pancreatic or bone marrow stem cells.
Patients recently diagnosed (less than 6 months) with type 1 diabetes mellitus proved by positive antibody against glutamic acid decarboxylase will be included in this study. Hematopoietic stem cells will be mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colonystimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were injected intravenously after conditioning with cyclophosphamide (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). This procedure is performed in isolated rooms at the Bone Marrow Transplantation Unit of Shanghai Ruijin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine. Patients will be discharged from the hospital 1 month after transplantation and continue the follow-ups for 3 years. Patients fitting the inclusion criteria but not agreeing to perform the transplantation are the control group and they will be followed in parallel with transplanted patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 diabetes mellitus diagnosed by clinical/metabolic parameters and positive anti-GAD antibody
- •Less than 6 months from diagnosis
排除标准
- •Previous diabetic ketoacidosis
- •Pregnancy
- •Severe psychiatric disorder
- •Severe organic impairment (renal, hepatic, cardiac, pulmonary)
- •Active infectious disease
- •Previous or present neoplastic disease
研究组 & 干预措施
insulin therapy
The participants not accepted written informed consent will receive insulin therapy
干预措施: Insulin therapy (Drug)
AHSCT
The participants accepted written informed consent will receive the therapy of autologous hematopoietic stem cell transplantation(AHSCT)
干预措施: AHSCT (Procedure)
结局指标
主要结局
Exogenous insulin dose
时间窗: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
次要结局
- Anti-GAD titres(1 month, 3 months, 6 months, 12 months, 24 months, 36 months)
- HbA1c level(3 months, 6 months, 12 months, 24 months, 36 months)
- C-peptide level(1 month, 3 months, 6 months, 12 months, 24 months, 36 months)
研究者
Guang Ning
Director
Shanghai Jiao Tong University School of Medicine