Prospective Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Changes in C-peptide levels during standard-meal tolerance test from baseline to different time points after transplantation
研究概览
简要总结
Type 1 diabetes is an autoimmune disease and results from T cell autoimmunity mediated destruction of the majority of insulin-producing pancreatic β-cells. Hence,the development of new therapies to control T cell autoimmunity, and to preserve the remaining β-cell function will be of great significance in managing patients with type 1 diabetes
Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) has been tested for the treatment of patients with new onset of type 1 diabetes. This therapeutic strategy can result in exogenous insulin independence by destroying pathogenic memory T cells and preserving the remaining β-cell function.
However, little is known about the efficacy of AHST in the dynamics of immunocompetent cell reconstitution and how the reconstituted immune system regulates β-cell specific antibody response. Furthermore, many Chinese patients at diagnosis of type 1 diabetes have progressed to develop diabetic ketoacidosis (DKA). Whether treatment with AHST could still achieve adequate glycemic control and preserve the β-cell function and what the factors are associated with the therapeutic efficacy have not been explored.
This is a phase Ⅱ clinical trial in patients who have been diagnosed with type 1 diabetes within the previous 12 months.This study is to determine:
- The effects of autologous hematopoietic stem cell transplantation on the reconstitution of immune system
- β-cell preservation following stem cell transplantation
- The potential factors affecting efficacy of stem cell transplantation
- Whether this new therapy is safe.
详细描述
Patients diagnosed with type 1 diabetes within the previous 12 months will be recruited into this study.Hematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0g/m2) and granulocyte colony stimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). All the included patients undergoing AHST complied with blood glucose self-monitoring and scheduled medical appointments.Their blood samples were obtained for measuring the frequency of lymphocytes and the levels of plasma hemoglobin A1c (HbA1c), serum C-peptide, islet antibodies, and cytokines longitudinally.
Ages Eligible for Study: no more than 35 years
Genders Eligible for Study: both
Islet Autoantibodies Eligible for Study: positive for glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or insulin autoantibody (IAAs)
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
- 8 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •diagnosis of diabetes according to the guidelines of the World Health Organization 1999
- •the duration of diabetes is no more than 12 months
- •positive for for glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or insulin autoantibody (IAAs)
排除标准
- •pregnancy
- •mental disorders
- •blood diseases
- •the presence of any other severe diseases that could potentially influence the transplantation outcomes
结局指标
主要结局
Changes in C-peptide levels during standard-meal tolerance test from baseline to different time points after transplantation
时间窗: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
次要结局
- Temporal changes of exogenous insulin requirement from baseline to different time points after transplantation(3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years)
- Dynamic changes in lymphocyte immunophenotyping and cytokine profiles from baseline to different time points after transplantation(3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years)
- mortality and dysfunction of other endocrine glands(up to 10 years)
- Changes in serum levels of HbA1c from baseline to different time points after transplantation(3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years)
- Dynamic changes in islet antibody status from baseline to different time points after transplantation(3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years)
研究者
Dalong Zhu
Chief Physician
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School