NCT01341899

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2006

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2006

Completed
4.9 years until next milestone

First Submitted

Initial submission to the registry

April 21, 2011

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 26, 2011

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
Last Updated

November 1, 2016

Status Verified

October 1, 2016

Enrollment Period

6.5 years

First QC Date

April 21, 2011

Last Update Submit

October 31, 2016

Conditions

Keywords

Type 1 diabetesstem cellC-peptideImmune function

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (5)

  • 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

  • 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

  • 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

  • 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

  • mortality and dysfunction of other endocrine glands

    up to 10 years

Study Arms (1)

stem cell transplantation

EXPERIMENTAL
Procedure: immunosuppression and stem cell transplantation

Interventions

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).

Also known as: nonmyeloablative stem cell transplantation
stem cell transplantation

Eligibility Criteria

Age8 Years - 35 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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)

You may not qualify if:

  • pregnancy
  • mental disorders
  • blood diseases
  • the presence of any other severe diseases that could potentially influence the transplantation outcomes

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Nanjing, Jiangsu, 210008, China

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Immunosuppression TherapyStem Cell Transplantation

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

ImmunotherapyImmunomodulationBiological TherapyTherapeuticsImmunologic TechniquesInvestigative TechniquesCell TransplantationCell- and Tissue-Based TherapyTransplantationSurgical Procedures, Operative

Study Officials

  • Dalong Zhu, MD,PhD

    the Affiliated Drum Tower Hospital of Nanjing University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief Physician

Study Record Dates

First Submitted

April 21, 2011

First Posted

April 26, 2011

Study Start

June 1, 2006

Primary Completion

December 1, 2012

Study Completion

December 1, 2015

Last Updated

November 1, 2016

Record last verified: 2016-10

Locations