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

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: 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: type 1 diabetes

MedlinePlus related topics: Diabetes Type 1

U.S. FDA Resources

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).

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:

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:

Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simões 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.

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. doi: 10.1001/jama.2009.470.

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.


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 16, 2017