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

This study has been completed.
Sponsor:
Collaborators:
Northwestern University
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Julio C. Voltarelli, University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT00315133
First received: April 13, 2006
Last updated: January 13, 2017
Last verified: January 2017
  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 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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 Julio C. Voltarelli, University of Sao Paulo:

Primary Outcome Measures:
  • C-peptide levels [ Time Frame: Every 6 months ]
    Stimulated C-peptide levels will be measured.


Secondary Outcome Measures:
  • Transplant-related toxicity [ Time Frame: Every 6 months or when reported ]
  • Anti-GAD titres [ Time Frame: Every 6 months ]
  • Exogenous insulin dose [ Time Frame: Every 6 months ]
    Number of international insulin units per kilogram per day in use will be registered.

  • Hemoglobin A1C [ Time Frame: Every 6 months ]
    Hb A1C will be measured.

  • Immunologic reconstitution parameters [ Time Frame: Yearly ]
  • Quality of Life [ Time Frame: Every year ]
    SF-36 questionnaire


Enrollment: 25
Study Start Date: December 2003
Study Completion Date: December 2014
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transplant arm
This is a single arm study. The intervention is immunosuppression and autologous stem cell transplantation.
Procedure: 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).

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

Ages Eligible for Study:   12 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
Ribeirão Preto, Brazil, 14048-900
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
Study Chair: Maria C Oliveira, MD PhD University Hospital, Ribeirão Preto Medical School, Brazil
  More Information

Additional Information:
Publications:
Responsible Party: Julio C. Voltarelli, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT00315133     History of Changes
Other Study ID Numbers: HCFMRPUSP
Study First Received: April 13, 2006
Last Updated: January 13, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: IPD may be shared if the responsible investigators feel it may increase understanding, reliability and reproducibility of the present study.

Keywords provided by Julio C. Voltarelli, 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 August 23, 2017