Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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: 
      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.
    

Intervention name(s): Autologous hematopoietic stem cell transplantation
Intervention type(s): Procedure
Intervention description(s): 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.
Other intervention name(s): Stem cell therapy
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment