Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes

Sponsor

Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT00807651

Collaborator

(none)

Enrollment

Location

Arms

106

Actual Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus	Procedure: AHSCT Drug: Insulin therapy	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

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

Actual Study Start Date :

Feb 1, 2008

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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 Names: insulin injection therapy
Experimental: AHSCT The participants accepted written informed consent will receive the therapy of autologous hematopoietic stem cell transplantation(AHSCT)	Procedure: AHSCT All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression. Other Names: hematopoietic stem cell

Arm

Intervention/Treatment

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 Names:

insulin injection therapy

Experimental: AHSCT

The participants accepted written informed consent will receive the therapy of autologous hematopoietic stem cell transplantation(AHSCT)

Procedure: AHSCT

All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression.

Other Names:

hematopoietic stem cell