Type 1 Diabetes
Conditions
Keywords
Type 1 diabetes, stem cell, C-peptide, Immune function
Brief summary
Type 1 diabetes is an autoimmune disease and results from T cell autoimmunity mediated destruction of the majority of insulin-producing pancreatic β-cells. Hence,the development of new therapies to control T cell autoimmunity, and to preserve the remaining β-cell function will be of great significance in managing patients with type 1 diabetes Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) has been tested for the treatment of patients with new onset of type 1 diabetes. This therapeutic strategy can result in exogenous insulin independence by destroying pathogenic memory T cells and preserving the remaining β-cell function. However, little is known about the efficacy of AHST in the dynamics of immunocompetent cell reconstitution and how the reconstituted immune system regulates β-cell specific antibody response. Furthermore, many Chinese patients at diagnosis of type 1 diabetes have progressed to develop diabetic ketoacidosis (DKA). Whether treatment with AHST could still achieve adequate glycemic control and preserve the β-cell function and what the factors are associated with the therapeutic efficacy have not been explored. This is a phase Ⅱ clinical trial in patients who have been diagnosed with type 1 diabetes within the previous 12 months.This study is to determine: * The effects of autologous hematopoietic stem cell transplantation on the reconstitution of immune system * β-cell preservation following stem cell transplantation * The potential factors affecting efficacy of stem cell transplantation * Whether this new therapy is safe.
Detailed description
Patients diagnosed with type 1 diabetes within the previous 12 months will be recruited into this study.Hematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0g/m2) and granulocyte colony stimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). All the included patients undergoing AHST complied with blood glucose self-monitoring and scheduled medical appointments.Their blood samples were obtained for measuring the frequency of lymphocytes and the levels of plasma hemoglobin A1c (HbA1c), serum C-peptide, islet antibodies, and cytokines longitudinally. Ages Eligible for Study: no more than 35 years Genders Eligible for Study: both Islet Autoantibodies Eligible for Study: positive for glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or insulin autoantibody (IAAs)
Interventions
PROCEDUREimmunosuppression and stem cell transplantation
Hematopoietic stem cells were mobilized with cyclophosphamide (CY, 2.0 g/m2) and granulocyte colonystimulating factor (10 μg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were infused after conditioning with CY (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg).
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* diagnosis of diabetes according to the guidelines of the World Health Organization 1999 * the duration of diabetes is no more than 12 months * positive for for glutamic acid decarboxylase antibody (GADA), protein tyrosine phosphatase antibody (IA-2A), islet cell antibody (ICA) and/or insulin autoantibody (IAAs)
Exclusion criteria
* pregnancy * mental disorders * blood diseases * the presence of any other severe diseases that could potentially influence the transplantation outcomes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in C-peptide levels during standard-meal tolerance test from baseline to different time points after transplantation | 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years |
Secondary
| Measure | Time frame |
|---|---|
| Changes in serum levels of HbA1c from baseline to different time points after transplantation | 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years |
| Temporal changes of exogenous insulin requirement from baseline to different time points after transplantation | 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years |
| Dynamic changes in islet antibody status from baseline to different time points after transplantation | 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years |
| Dynamic changes in lymphocyte immunophenotyping and cytokine profiles from baseline to different time points after transplantation | 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years |
| mortality and dysfunction of other endocrine glands | up to 10 years |
Countries
China
Outcome results
None listed