Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety and Efficacy Study of Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes-a Phase II Study

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Procedure: AHSCT
* Drug: Insulin therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes mellitus diagnosed by clinical/metabolic parameters and positive anti-GAD antibody Less than 6 months from diagnosis Exclusion Criteria: Previous diabetic ketoacidosis Pregnancy Severe psychiatric disorder Severe organic impairment (renal, hepatic, cardiac, pulmonary) Active infectious disease Previous or present neoplastic disease

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: insulin therapy<br>The participants not accepted written informed consent will receive insulin therapy | Drug: Insulin therapy<br>* All study participants not accepted written informed consent will received insulin therapy with consistent or multiply subcutaneous injection.<br>* Other names: insulin injection therapy;|
| Experimental: AHSCT<br>The participants accepted written informed consent will receive the therapy of autologous hematopoietic stem cell transplantation(AHSCT) | Procedure: AHSCT<br>* All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression.<br>* Other names: hematopoietic stem cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exogenous insulin dose |  | 1 month, 3 months, 6 months, 12 months, 24 months, 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-GAD titres |  | 1 month, 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 | 
| HbA1c level |  | 3 months, 6 months, 12 months, 24 months, 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Stem cells, Autologous stem cell transplantation, Autoimmune diseases