Clinical trial NCT00807651: Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes
Official title: Safety and Efficacy Study of Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes-a Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Keywords: Diabetes Mellitus
Stem cells
Autologous stem cell transplantation
Autoimmune diseases
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2008-12-12
Enrollment: 40
Sex: ALL
Minimum age (years): 14
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Exogenous insulin dose
timeFrame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
Secondary outcomes:
measure: Anti-GAD titres
timeFrame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
measure: C-peptide level
timeFrame: 1 month, 3 months, 6 months, 12 months, 24 months, 36 months
measure: HbA1c level
timeFrame: 3 months, 6 months, 12 months, 24 months, 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine
name: Guang Ning, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KC, Foss-Freitas MC, Simoes 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. doi: 10.1001/jama.297.14.1568.
citation: Ye L, Li L, Wan B, Yang M, Hong J, Gu W, Wang W, Ning G. Immune response after autologous hematopoietic stem cell transplantation in type 1 diabetes mellitus. Stem Cell Res Ther. 2017 Apr 18;8(1):90. doi: 10.1186/s13287-017-0542-1.
citation: Gu W, Hu J, Wang W, Li L, Tang W, Sun S, Cui W, Ye L, Zhang Y, Hong J, Zhu D, Ning G. Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes. Diabetes Care. 2012 Jul;35(7):1413-9. doi: 10.2337/dc11-2161.
citation: Zhang X, Ye L, Hu J, Tang W, Liu R, Yang M, Hong J, Wang W, Ning G, Gu W. Acute response of peripheral blood cell to autologous hematopoietic stem cell transplantation in type 1 diabetic patient. PLoS One. 2012;7(2):e31887. doi: 10.1371/journal.pone.0031887. Epub 2012 Feb 22.