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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes Mellitus- a Phase I/II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00315133
• Other study ID #: HCFMRPUSP
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 13, 2006
• Last updated: January 13, 2017
• Start date: December 2003
• Est. completion date: December 2014

Study information

• Verified date: January 2017
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 2014
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

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).

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto

Sponsors (3)

Lead Sponsor	Collaborator
University of Sao Paulo	Genzyme, a Sanofi Company, Northwestern University

Country where clinical trial is conducted

Brazil, 

References & Publications (3)

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. — View Citation

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 hemat — View Citation

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 diab — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C-peptide levels	Stimulated C-peptide levels will be measured.	Every 6 months
Secondary	Transplant-related toxicity		Every 6 months or when reported
Secondary	Anti-GAD titres		Every 6 months
Secondary	Exogenous insulin dose	Number of international insulin units per kilogram per day in use will be registered.	Every 6 months
Secondary	Hemoglobin A1C	Hb A1C will be measured.	Every 6 months
Secondary	Immunologic reconstitution parameters		Yearly
Secondary	Quality of Life	SF-36 questionnaire	Every year

External Links

•   General information about the blood and research center where stem cells are collected and where immunologic studies are performed
•   General information about the institution where the trial is conducted