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

NCT ID: NCT01341899

Last Updated: 2016-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2015-12-31

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)

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes; stem cell; C-peptide; Immune function

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

stem cell transplantation

Group Type: EXPERIMENTAL

immunosuppression and stem cell transplantation

Intervention Type: PROCEDURE

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).

Interventions

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).

Intervention Type: PROCEDURE

Other Intervention Names

nonmyeloablative stem cell transplantation

Eligibility Criteria

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

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

OTHER

Sponsor Role: lead

Responsible Party

Dalong Zhu

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dalong Zhu, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

the Affiliated Drum Tower Hospital of Nanjing University

Locations

at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University

Nanjing, Jiangsu, China

Countries

China

References

Li L, Shen S, Ouyang J, Hu Y, Hu L, Cui W, Zhang N, Zhuge YZ, Chen B, Xu J, Zhu D. Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves beta-cell function in Chinese patients with new onset of type 1 diabetes. J Clin Endocrinol Metab. 2012 May;97(5):1729-36. doi: 10.1210/jc.2011-2188. Epub 2012 Mar 14.

Reference Type: DERIVED

PMID: 22419704 (View on PubMed)

Other Identifiers

ZKX07012

Identifier Type: -

Identifier Source: org_study_id