Efficacy and Safety Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Type 1 Diabetes |
Procedure: immunosuppression and stem cell transplantation |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Prospective Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes |
- Changes in C-peptide levels during standard-meal tolerance test from baseline to different time points after transplantation [ Time Frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years ] [ Designated as safety issue: No ]
- Changes in serum levels of HbA1c from baseline to different time points after transplantation [ Time Frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years ] [ Designated as safety issue: No ]
- Temporal changes of exogenous insulin requirement from baseline to different time points after transplantation [ Time Frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years ] [ Designated as safety issue: No ]
- Dynamic changes in islet antibody status from baseline to different time points after transplantation [ Time Frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years ] [ Designated as safety issue: No ]
- Dynamic changes in lymphocyte immunophenotyping and cytokine profiles from baseline to different time points after transplantation [ Time Frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years ] [ Designated as safety issue: No ]
- mortality and dysfunction of other endocrine glands [ Time Frame: up to 10 years ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 50 |
| Study Start Date: | June 2006 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | December 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: stem cell transplantation |
Procedure: immunosuppression 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).
Other Name: nonmyeloablative stem cell transplantation
|
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)
Eligibility| Ages Eligible for Study: | 8 Years to 35 Years |
| Genders Eligible for Study: | Both |
| Accepts 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
Contacts and Locations| Contact: Dalong Zhu, MD, PhD | 86-25-83-105302 | zhudldr@gmail.com |
| Contact: Lirong Li, MD | 86-25-83-105302 | linglinglirong@yahoo.com.cn |
| China, Jiangsu | |
| at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University | Recruiting |
| Nanjing, Jiangsu, China, 210008 | |
| Contact: Dalong Zhu, MD,PhD 86-25-83-105302 zhudldr@gmail.com | |
| Contact: Lirong Li, MD 86-25-83-105302 linglinglirong@yahoo.com.cn | |
| Principal Investigator: Dalong Zhu, MD,PhD | |
| Sub-Investigator: Lirong Li, MD | |
| Principal Investigator: | Dalong Zhu, MD,PhD | the Affiliated Drum Tower Hospital of Nanjing University |
More Information
No publications provided by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Prospective Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes, Zhu Dalong |
| ClinicalTrials.gov Identifier: | NCT01341899 History of Changes |
| Other Study ID Numbers: | ZKX07012 |
| Study First Received: | April 21, 2011 |
| Last Updated: | July 25, 2011 |
| Health Authority: | China: Ethics Committee |
Keywords provided by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School:
|
Type 1 diabetes stem cell C-peptide Immune function |
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 May 23, 2013