Efficacy and Safety Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

Prospective Study of Autologous Hematopoietic Stem Cell Transplantation to Treat New Onset Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01341899
• Other study ID #: ZKX07012
• Status: Completed
• Phase: Phase 2
• First received: April 21, 2011
• Last updated: October 31, 2016
• Start date: June 2006
• Est. completion date: December 2015

Study information

• Verified date: October 2016
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2015
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 35 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

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).

Locations

Country	Name	City	State
China	at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	mortality and dysfunction of other endocrine glands		up to 10 years	Yes