Safety and Efficacy Study of Autologous Stem Cell Transplantation for Early Onset Type I Diabetes Mellitus

Study Overview
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Brief Summary
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The study evaluates the effect of inactivation of the immune system with chemotherapy and immunotherapy and infusion of bone marrow stem cells in early onset type 1 diabetes mellitus. We hypothesize that reprograming the immune system will stop immune aggression to the insulin producing cells allowing their regeneration and thus decreasing or eliminating the need of exogenous insulin.

Detailed Description
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Patients from 12 to 35 years old with type I diabetes mellitus proved by anti-pancreatic beta cell antibodies and recently diagnosed (less than 6 weeks) will be included in this study. Peripheral blood hematopoietic stem cells will be mobilized from bone marrow of the patient with cyclophosphamide plus G-CSF (granulocyte-colony stimulating factor), collected by leukapheresis and cryopreserved. After 2-3 weeks, high dose immunosuppression is given (cyclophosphamide 200 mg/kg plus rabbit antithymocyte globulin 4.5 mg/kg) and stem cells are thawed and injected intravenously. This procedure is performed in isolated rooms at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. Patients are discharged from the hospital after engraftment and closely followed up to 2 months after transplantation (with at least weekly outpatient visits) and continue the followup for 5 years after transplantation. Clinical, hematological, metabolical and immunological evaluations are performed to analyse the effect of the transplant in the disease and in the hematopoetic and immunologic systems of the body. 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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Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes Mellitus- a Phase I/II Study

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Procedure: Immunosuppression and autologous stem cell transplantation


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 antibodies Less than 12 weeks 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: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transplant arm<br>This is a single arm study. The intervention is immunosuppression and autologous stem cell transplantation. | Procedure: Immunosuppression and autologous stem cell transplantation<br>* Immunosuppression and autologous stem cell transplantation: Mobilization of hematopoietic stem cells (HSC) with cyclophosphamide (2 g/m2) and granulocyte-colony stimulating factor (G-CSF, 10 ug/kg/d), followed by collection and cryopreservation of unselected HSC and conditioning with cyclophosphamide (200 mg/kg) plus rabbit anti-thymocyte globulin (ATG 4.5 mg/kg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-peptide levels | Stimulated C-peptide levels will be measured. | Every 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant-related toxicity |  | Every 6 months or when reported | 
| Anti-GAD titres |  | Every 6 months | 
| Exogenous insulin dose | Number of international insulin units per kilogram per day in use will be registered. | Every 6 months | 
| Hemoglobin A1C | Hb A1C will be measured. | Every 6 months | 
| Immunologic reconstitution parameters |  | Yearly | 
| Quality of Life | SF-36 questionnaire | Every year | 

 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