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NCT Number: NCT01341899

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

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.

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Key information

Conditions

Type 1 Diabetes Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

8 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

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

Nanjing, Jiangsu, 210008, China

About this study

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)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

immunosuppression and stem cell transplantation

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).

Other names: nonmyeloablative stem cell transplantation

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. mortality and dysfunction of other endocrine glands

    Time frame: up to 10 years

Sponsors and collaborators

Lead sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Other

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2012
Study completion
2015
First posted
Apr 26, 2011
Registry last updated
Nov 1, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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