Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes
|Type 1 Diabetes Mellitus||Procedure: AHSCT Drug: Insulin therapy||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy Study of Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes-a Phase II Study|
- Exogenous insulin dose [ Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months ]
- Anti-GAD titres [ Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months ]
- C-peptide level [ Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months ]
- HbA1c level [ Time Frame: 3 months, 6 months, 12 months, 24 months, 36 months ]
|Study Start Date:||February 2008|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Active Comparator: insulin therapy
The participants not accepted written informed consent will receive insulin therapy
Drug: Insulin therapy
All study participants not accepted written informed consent will received insulin therapy with consistent or multiply subcutaneous injection.
Other Name: insulin injection therapy
The participants accepted written informed consent will receive the therapy of autologous hematopoietic stem cell transplantation(AHSCT)
All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression.
Other Name: hematopoietic stem cell
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00807651
|Shanghai Jiao Tong University School of Medicine|
|Shanghai, Shanghai, China, 200025|
|Principal Investigator:||Guang Ning, MD. PhD.||Shanghai Jiao Tong University School of Medicine|