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

NCT ID: NCT00315133

Last Updated: 2017-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-12-31
• Study Completion Date: 2014-12-31

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Transplant arm

This is a single arm study. The intervention is immunosuppression and autologous stem cell transplantation.

Group Type: EXPERIMENTAL

Immunosuppression and autologous stem cell transplantation

Intervention Type: 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).

Interventions

Immunosuppression and autologous stem cell transplantation

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).

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern University

OTHER

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Julio C. Voltarelli

Julio C. Voltarelli

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Julio C Voltarelli, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, School of Medicine of Ribeirão Preto, Brazil

Maria C Oliveira, MD PhD

Role: STUDY_CHAIR

University Hospital, Ribeirão Preto Medical School, Brazil

Locations

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirão Preto, Ribeirão Preto, Brazil

Countries

Brazil

References

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.

Reference Type: BACKGROUND

PMID: 12849006 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17426276 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19366777 (View on PubMed)

Other Identifiers

HCFMRPUSP

Identifier Type: -

Identifier Source: org_study_id