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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by University of Sao Paulo.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Northwestern University
Genzyme, a Sanofi Company
Information provided by:
University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT00315133
First received: April 13, 2006
Last updated: November 15, 2010
Last verified: November 2010
  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 1
Phase 2

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:


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:
    Procedure: Immunosuppression and autologous stem cell transplantation
    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).
    Procedure: Autologous hematopoietic stem cell transplantation
    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, a Sanofi Company
Investigators
Principal Investigator: Julio C Voltarelli, MD PhD University Hospital, School of Medicine of Ribeirão Preto, Brazil
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 April 16, 2014