Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): AHSCT; Insulin therapy
Intervention type(s): Procedure; Drug
Intervention description(s): All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression.; All study participants not accepted written informed consent will received insulin therapy with consistent or multiply subcutaneous injection.
Other intervention name(s): hematopoietic stem cell; insulin injection therapy
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes Mellitus; Stem cells; Autologous stem cell transplantation; Autoimmune diseases