Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes

November 16, 2021 updated by: Guang Ning, Shanghai Jiao Tong University School of Medicine

Safety and Efficacy Study of Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes-a Phase II Study

This is a phase II trial in individuals who have been diagnosed with type 1 diabetes within the previous 6 months. The study is evaluating whether stem cell transplantation is safe when chemotherapy and immunotherapy are used in combination and if it has immune resetting effect that may halt the immune attack to pancreas islets and thus preserve the body's own insulin production.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Generally, at the time someone is diagnosed with type 1 diabetes, not all of a person's beta cells have been destroyed. It's important to preserving the remaining precious beta cells so as to stop the diabetes progression.

The exact mechanism of action of Autologous Hematopoietic Stem Cell Transplantation(AHST) in autoimmune disorders is not fully understood. Preliminary data supported post-AHST immune resetting included an increase in thymus-derived naive T cells, decreased central-memory T cells, increased output of recent thymic emigrants, and recovery of a diverse but distinct T-cell receptor repertoire following AHST. In the patients of type 1 diabetes, decreasing titer of anti-GAD antibody may bring improvement of beta-cell function after intensive immunosuppression. Furthermore, there may exit the possibility of regeneration of beta cells from surviving beta cells or from pancreatic or bone marrow stem cells.

Patients recently diagnosed (less than 6 months) with type 1 diabetes mellitus proved by positive antibody against glutamic acid decarboxylase will be included in this study. Hematopoietic stem cells will be mobilized with cyclophosphamide (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 injected intravenously after conditioning with cyclophosphamide (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). This procedure is performed in isolated rooms at the Bone Marrow Transplantation Unit of Shanghai Ruijin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine. Patients will be discharged from the hospital 1 month after transplantation and continue the follow-ups for 3 years. Patients fitting the inclusion criteria but not agreeing to perform the transplantation are the control group and they will be followed in parallel with transplanted patients.

Study Type

Interventional

Enrollment (Actual)

40

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
    • Shanghai
      • Shanghai, Shanghai, China, 200025
        • Shanghai Jiao Tong University School of Medicine

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

14 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Type 1 diabetes mellitus diagnosed by clinical/metabolic parameters and positive anti-GAD antibody
  • Less than 6 months from diagnosis

Exclusion Criteria:

  • Previous diabetic ketoacidosis
  • Pregnancy
  • Severe psychiatric disorder
  • Severe organic impairment (renal, hepatic, cardiac, pulmonary)
  • Active infectious disease
  • Previous or present neoplastic disease

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: insulin therapy
The participants not accepted written informed consent will receive insulin therapy
Drug: Insulin therapy
All study participants not accepted written informed consent will received insulin therapy with consistent or multiply subcutaneous injection.
Other Names:
  • insulin injection therapy
Experimental: AHSCT
The participants accepted written informed consent will receive the therapy of autologous hematopoietic stem cell transplantation(AHSCT)
Procedure: AHSCT
All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression.
Other Names:
  • hematopoietic stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Exogenous insulin dose
Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
1 month, 3 months, 6 months, 12 months, 24 months, 36 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Anti-GAD titres
Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
1 month, 3 months, 6 months, 12 months, 24 months, 36 months
C-peptide level
Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
1 month, 3 months, 6 months, 12 months, 24 months, 36 months
HbA1c level
Time Frame: 3 months, 6 months, 12 months, 24 months, 36 months
3 months, 6 months, 12 months, 24 months, 36 months

Collaborators and Investigators

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

Sponsor

Shanghai Jiao Tong University School of Medicine

Investigators

  • Principal Investigator: Guang Ning, MD. PhD., Shanghai Jiao Tong University School of Medicine

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 (Actual)

February 1, 2008

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

December 11, 2008

First Submitted That Met QC Criteria

December 11, 2008

First Posted (Estimate)

December 12, 2008

Study Record Updates

Last Update Posted (Actual)

November 18, 2021

Last Update Submitted That Met QC Criteria

November 16, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCEMD006

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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