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

October 31, 2016 updated by: Dalong Zhu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Prospective 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210008
        • at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • nonmyeloablative stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
Time Frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
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
Time Frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
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
Time Frame: 3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
3 months, 6 months, 12 months, then yearly after transplantation, up to 10 years
mortality and dysfunction of other endocrine glands
Time Frame: up to 10 years
up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2015

Study Registration Dates

First Submitted

April 21, 2011

First Submitted That Met QC Criteria

April 25, 2011

First Posted (Estimate)

April 26, 2011

Study Record Updates

Last Update Posted (Estimate)

November 1, 2016

Last Update Submitted That Met QC Criteria

October 31, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZKX07012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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