Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to determine if autologous nonmyeloablative hematopoietic stem cell transplantation is able to induce prolonged and significant increases of C-peptide levels associated with absence of or reduction of daily insulin.

Detailed Description
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Patients with type 1 DM depend on exogenous insulin administration for survival and for control of long-term complications. The best-established treatment is tight control of blood glucose achieved by frequent daily injections or continuous subcutaneous infusion of insulin, ie, intensive insulin therapy. Although insulin therapy has developed enormously, even the most modern technologies do not allow the maintenance of normoglycemia. Since the establishment of the autoimmune etiology of type 1 DM in the late 1970s, many clinical trials analyzing the effects of different types of immune interventions demonstrated that beta-cell preservation is an achievable target in different degrees. Controlled trials and further biological studies are necessary to confirm the role of this treatment in changing the natural history of type 1 DM. This is a prospective pilot study which will enroll patients with type 1 diabetes mellitus within the first months of diagnosis, with clinical and laboratory findings. The donor stimulation will be with cyclophosphamide, filgrastim, and mesna. The cells will be recollected from peripheral blood by apheresis and refrigerated. The patients will receive a nonmyeloablative conditioning regimen with cyclophosphamide and fludarabine, and after this, the cells will be injected intravenously. They will receive a standard regimen of post-transplant prophylaxis. The duration of use of this prophylactic drugs scheme depends on the patient's recovery time. The reinfusion of stem cells will be completed after the last dose of cyclophosphamide, through a peripheral vein. Lately, every three months, the C-Peptide levels, glucose and insulin serum levels will be measured.

Official Title
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Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Procedure: Autologous hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly diagnosed in type 1 diabetes mellitus Exclusion Criteria: Patients with HIV Patients with Hepatitis Patients with hematologic disease Patients with hearth failure Renal, Hepatic or psychiatric disease Pregnant patients

Ages Eligible for Study
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Minimum Age: 2 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: Hematopoietic stem cells<br> | Procedure: Autologous hematopoietic stem cell transplantation<br>* Patients will receive a stimulation with filgrastim 10mcg/Kg per day during 4 days and cyclophosphamide 1.5g/m2 per day during 2 days and mesna 300mg/m2 i.v. in 4 hours for prophylaxis (uroprotection). Lately, the stem cells will be recollected by apheresis. After that, the patients will receive a conditioning regimen with cyclophosphamide 500mg/m2 per day during 4 days and fludarabine 30mg/m2 per day during 4 days. After the last dose of cyclophosphamide, the autologous hematopoietic stem cell transplantation will be done on day 0, by peripheral vein. Then, a standard regimen of prophylaxis with oral ciprofloxacin 500mg every 12 hours, acyclovir 400mg every 8 hours, fluconazole 100mg per day and omeprazole 20mg per day for the recovery time of each patient.<br>* Other names: Stem cell therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-peptide levels before and after the hematopoietic stem cell transplantation |  | Every 3 months for 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum levels of Hb A1C before and after the hematopoietic stem cell transplantation |  | Every month for 1 year. |