Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Northwestern University | OTHER |
| Genzyme, a Sanofi Company | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Transplant arm | Experimental | This is a single arm study. The intervention is immunosuppression and autologous stem cell transplantation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Immunosuppression and autologous stem cell transplantation | Procedure | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| C-peptide levels | Stimulated C-peptide levels will be measured. | Every 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Transplant-related toxicity | Every 6 months or when reported | |
| Anti-GAD titres | Every 6 months | |
| Exogenous insulin dose |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Julio C Voltarelli, MD PhD | University Hospital, School of Medicine of Ribeirão Preto, Brazil | Principal Investigator |
| Maria C Oliveira, MD PhD | University Hospital, Ribeirão Preto Medical School, Brazil | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital das ClÃnicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo | Ribeirão Preto | Ribeirão Preto | 14048-900 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12849006 | Background | Burt RK, Oyama Y, Traynor A, Kenyon NS. Hematopoietic stem cell therapy for type 1 diabetes: induction of tolerance and islet cell neogenesis. Autoimmun Rev. 2002 May;1(3):133-8. doi: 10.1016/s1568-9972(02)00033-2. | |
| 17426276 | Result | Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes BP, Foss MC, Squiers E, Burt RK. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76. doi: 10.1001/jama.297.14.1568. |
Not provided
Not provided
IPD may be shared if the responsible investigators feel it may increase understanding, reliability and reproducibility of the present study.
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003920 | Diabetes Mellitus |
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D007165 | Immunosuppression Therapy |
| ID | Term |
|---|---|
| D007167 | Immunotherapy |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
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 |
| 19366777 | Result | Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simoes BP, Martinez EZ, Foss MC, Burt RK, Voltarelli JC. C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2009 Apr 15;301(15):1573-9. doi: 10.1001/jama.2009.470. |
| D007154 | Immune System Diseases |
| D007158 |
| Immunologic Techniques |
| D008919 | Investigative Techniques |