Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes

Type 1 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00807651
• Other study ID #: CCEMD006
• Status: Completed
• Phase: Phase 2
• Start date: February 2008
• Est. completion date: December 2016

Study information

• Verified date: November 2021
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Procedure:
• AHSCT
All study participants given written informed consent will perform autologous hematopoietic stem cell transplantation(AHSCT) and be treated with immunosuppression.

Drug:
• Insulin therapy
All study participants not accepted written informed consent will received insulin therapy with consistent or multiply subcutaneous injection.

Locations

Country	Name	City	State
China	Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Jiao Tong University School of Medicine

Country where clinical trial is conducted

China, 

References & Publications (1)

Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simões BP, Foss MC, Squiers E, Burt RK. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exogenous insulin dose		1 month, 3 months, 6 months, 12 months, 24 months, 36 months
Secondary	Anti-GAD titres		1 month, 3 months, 6 months, 12 months, 24 months, 36 months
Secondary	C-peptide level		1 month, 3 months, 6 months, 12 months, 24 months, 36 months
Secondary	HbA1c level		3 months, 6 months, 12 months, 24 months, 36 months