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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2011 by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor:
Information provided by:
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
ClinicalTrials.gov Identifier:
NCT01341899
First received: April 21, 2011
Last updated: July 25, 2011
Last verified: July 2011
  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

Resource links provided by NLM:


Further study details as provided by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01341899

Contacts
Contact: Dalong Zhu, MD, PhD 86-25-83-105302 zhudldr@gmail.com
Contact: Lirong Li, MD 86-25-83-105302 linglinglirong@yahoo.com.cn

Locations
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         
Sponsors and Collaborators
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Investigators
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
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on November 23, 2014