Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Guang Ning, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier:
NCT00807651
First received: December 11, 2008
Last updated: February 15, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Procedure: Immunosuppression and autologous stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy Study of Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes-a Phase II Study

Resource links provided by NLM:


Further study details as provided by Shanghai Jiao Tong University School of Medicine:

Primary Outcome Measures:
  • Exogenous insulin dose [ Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Anti-GAD titres [ Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months ] [ Designated as safety issue: No ]
  • C-peptide level [ Time Frame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months ] [ Designated as safety issue: No ]
  • HbA1c level [ Time Frame: 3 months, 6 months, 12 months, 24 months, 36 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: February 2008
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: insulin therapy
The participants not accepted written informed consent will receive insulin therapy
Procedure: Immunosuppression and autologous stem cell transplantation
All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation.
Other Name: hematopoietic stem cell

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.

  Eligibility

Ages Eligible for Study:   14 Years to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00807651

Locations
China, Shanghai
Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai, China, 200025
Sponsors and Collaborators
Shanghai Jiao Tong University School of Medicine
Investigators
Principal Investigator: Guang Ning, MD. PhD. Shanghai Jiao Tong University School of Medicine
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Guang Ning, Director, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT00807651     History of Changes
Other Study ID Numbers: CCEMD006
Study First Received: December 11, 2008
Last Updated: February 15, 2014
Health Authority: China: Ethics Committee

Keywords provided by Shanghai Jiao Tong University School of Medicine:
Diabetes Mellitus
Stem cells
Autologous stem cell transplantation
Autoimmune diseases

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