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

Sponsor:	University of Sao Paulo
Collaborators:	Northwestern University Genzyme
Information provided by:	University of Sao Paulo
ClinicalTrials.gov Identifier:	NCT00315133

Purpose

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.

Condition	Intervention	Phase
Type 1 Diabetes Mellitus	Procedure: Immunosuppression and autologous stem cell transplantation Procedure: Autologous hematopoietic stem cell transplantation	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes Mellitus- a Phase I/II Study

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Autoimmune Diseases Diabetes Medicines Diabetes Type 1

U.S. FDA Resources

Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:

Exogenous insulin dose [ Time Frame: Daily ] [ Designated as safety issue: Yes ]
C-peptide levels [ Time Frame: Each 6 months ] [ Designated as safety issue: No ]
Hemoglobin A1c [ Time Frame: Each 3 months ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: Each 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Anti-GAD titres [ Time Frame: Each 6 months ] [ Designated as safety issue: No ]
Immunologic reconstitution parameters [ Time Frame: Yearly ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	December 2003
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Mobilization of hematopoietic stem cells (HSC) with cyclophosphamide (2 g/m2) and G-CSF (10 ug/kg/d), followed by collection and freezing of HSC and conditioning with cyclophosphamide (200 mg/kg) plus rabbit ATG (4,5 mg/kg).

Mobilization of hematopoietic stem cells (HSC) to peripheral blood with G-CSF (10 ug/kg/d) and cyclophosphamide (2 g/m2) followed by collection and freezing of HSC and high dose chemotherapy with cyclophosphamide again (200 mg/kg) plus rabbit antithymocyte globulin (4,5 mg/kg).

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, 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

Ages Eligible for Study:	12 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00315133

Contacts

Contact: Julio C Voltarelli, MD	55-16-2101-9369	jcvoltar@fmrp.usp.br
Contact: Eduardo B Couri, MD	55-16-9149-5151	ce.couri@yahoo.com.br

Locations

Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Recruiting
Ribeirão Preto, Brazil, 14048-900
Contact: Julio C Voltarelli, MD PhD 55-16-2101-9369 jcvoltar@fmrp.usp.br
Principal Investigator: Julio C Voltarelli, MD PhD

Sponsors and Collaborators

University of Sao Paulo

Northwestern University

Genzyme

Investigators

Principal Investigator:

Julio C Voltarelli, MD PhD

University Hospital, School of Medicine of Ribeirão Preto, Brazil

More Information

Additional Information:

General information about the institution where the trial is conducted This link exits the ClinicalTrials.gov site

General information about the blood and research center where stem cells are collected and where immunologic studies are performed This link exits the ClinicalTrials.gov site

Publications:

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. Review.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simões 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.

Responsible Party:	Julio Voltarelli MD PhD, University of São Paulo, School of Medicine of Ribeirão Preto
ClinicalTrials.gov Identifier:	NCT00315133 History of Changes
Other Study ID Numbers:	HCFMRPUSP
Study First Received:	April 13, 2006
Last Updated:	November 15, 2010
Health Authority:	Brazil: Ministry of Health

Keywords provided by University of Sao Paulo:

Diabetes mellitus
Stem cells
Autologous stem cell transplantation
Autoimmune diseases

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases

Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on February 07, 2012