Clinical trial NCT00315133: Safety and Efficacy Study of Autologous Stem Cell Transplantation for Early Onset Type I Diabetes Mellitus
Official title: Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes Mellitus- a Phase I/II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Type 1 Diabetes Mellitus
Keywords: Diabetes mellitus
Stem cells
Autologous stem cell transplantation
Autoimmune diseases
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Northwestern University
name: Genzyme, a Sanofi Company
First posted: 2006-04-17
Enrollment: 25
Sex: ALL
Minimum age (years): 12
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: C-peptide levels
timeFrame: Every 6 months
Secondary outcomes:
measure: Transplant-related toxicity
timeFrame: Every 6 months or when reported
measure: Anti-GAD titres
timeFrame: Every 6 months
measure: Exogenous insulin dose
timeFrame: Every 6 months
measure: Hemoglobin A1C
timeFrame: Every 6 months
measure: Immunologic reconstitution parameters
timeFrame: Yearly
measure: Quality of Life
timeFrame: Every year
Other outcomes:
Locations:
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
Study officials:
affiliation: University Hospital, School of Medicine of Ribeirão Preto, Brazil
name: Julio C Voltarelli, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Ribeirão Preto Medical School, Brazil
name: Maria C Oliveira, MD PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.