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

Phase 1

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Procedure: Immunosuppression and autologous stem cell transplantation

• Registration Number: NCT00315133
• Lead Sponsor: University of Sao Paulo

Brief 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.

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.

Study Timeline

• Study Start: 2003-12
• Study First Submitted: 2006-04-13
• Study First Submitted QC: 2006-04-13
• Study First Posted: 2006-04-17
• Primary Completion: 2010-12
• Study Completion: 2014-12
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-13
• Last Update Posted: 2017-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• Type 1 diabetes mellitus diagnosed by clinical/metabolic parameters and positive anti-GAD antibodies
• Less than 12 weeks from diagnosis

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Exclusion Criteria

• Previous diabetic ketoacidosis
• Pregnancy
• Severe psychiatric disorder
• Severe organic impairment (renal, hepatic, cardiac, pulmonary)
• Active infectious disease
• Previous or present neoplastic disease

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Transplant arm	Immunosuppression and autologous stem cell transplantation	This is a single arm study. The intervention is immunosuppression and autologous stem cell transplantation.

Primary Outcome Measures

Name	Time	Method
C-peptide levels	Every 6 months	Stimulated C-peptide levels will be measured.

Secondary Outcome Measures

Name	Time	Method
Hemoglobin A1C	Every 6 months	Hb A1C will be measured.
Transplant-related toxicity	Every 6 months or when reported
Anti-GAD titres	Every 6 months
Quality of Life	Every year	SF-36 questionnaire
Exogenous insulin dose	Every 6 months	Number of international insulin units per kilogram per day in use will be registered.
Immunologic reconstitution parameters	Yearly

Trial Locations

Locations (1)

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo; 🇧🇷 Ribeirão Preto, Brazil