Type 1 Diabetes
Conditions
Keywords
Type1 diabetes, porcine islets, treg cells, immunosuppress, xenotransplantation
Brief summary
The neonatal pig islets will be used as donor culturing with our modified culture medium. At the same time the autologous T regulatory cells will be used to induce specific immune tolerance for porcine islets grafts combined the costimulation of T cell activation channel blockers. The treatment for type 1 diabetes will be evaluated the efficacy and safety.
Interventions
OTHERPorcine islets
Porcine islets: 10000IEQ/Kg; Tacrolimus: 0.087mg/kg, Bid; mycophemo-latemofetil (MMF): 1g x 2/d; NULOJIX(belatacept): Day 1 (prior to transplantation), Day 5, Week 2, Week 4, Week 8, Week 12 10mg/kg
OTHERAutologous Treg
Autologous Treg: 2x10\^6/Kg
Sponsors
Hunan Xeno-life Science Ltd
Wei Wang,MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients age 18 to 40 years of age; * Type 1 diabetes mellitus for at least 5 years; * Body weight 40 to 60kg; * Ability to provide written informed consent; * Manifest signs and symptoms that are severe enough to be incapacitating; * Patients with poor diabetes control (HbA1c \> 9% ); * Patients have diabetes ketoacidosis or hypoglycemia more than once
Exclusion criteria
* Age \< 18 years or \> 60 years; * Diabetes history \< 5 years; * Body weight \> 80 kg; * Exogenous insulin requirement \> 1 unit/kg/day; * Blood test: hemoglobin male \< 90g/l, female \< 90 g/l) or Wbc \<3×109/L, lymphocyte \<1.5×10\^9/L; or platelet \< 80×10\^9/L; activated- partial-thromboplastin-time （APTT） \> normal value (31-43s)10s; * Liver dysfunction; * Kidney dysfunction; * Cardiopulmonary dysfunction; * Combined mental illness, cancer, infection, severe trauma, pancreatitis, surgery or other stress situations for patients; gastric ulcer patients, any bleeding disorders, tuberculosis infection and active infection including hepatitis B, hepatitis C, HIV, or John Cunningham virus; * Serological detection Epstein-Barr virus (EBV) or Cytomegalovirus (CMV)negative; * Patient have taken immunosuppressant in recent one year With high incidence of malignancy in three generation; * Women not using effective contraception of childbearing age, or planning pregnancy in nearly two years or being pregnant or lactating; * Patients can not comply with the research program to complete the diagnosis and treatment; * Patients not be passed by Ethics committee
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood glucose | 1 year | Before and after transplantation the patient will be tested the blood glucose. If the blood glucose within 24 hours is stable and no occurrence of diabetic ketoacidosis and hypoglycemia.Thirty percent reduction of exogenous insulin requirement will be considered as effective. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Porcine C-peptide | 1 years | The patient will be detected the porcine C-peptide levels after transplantion every three months. |
| Hemoglobin A1c | 1 years | After transplantation the patient will be checked hemoglobin A1c every month.The level of HbA1c less than 6.5% was considered as effective. |
| AST | 1 years | AST will be tested every three months. |
| ALT | 1 years | ALT will be tested every three months. |
| Scr | 1 years | Scr will be tested every three months. |
| Virus detection | 2 years | The recipient's serum and peripheral blood monouclear cells (PBMC) will be collected for virus detection every six months. |
| Ultrasonic examination for liver | 1 years | Ultrasonic examination will be used for the recipient's liver before transplantation and every three month post transplantation. |
| MRI for liver | 1 years | MRI will be used for liver before transplantaion and every three month post transplantation. |
| Immune cells detection | 1 years | The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected for immune cell's analysis. |
| Cytokine detection | 1 years | The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected cytokine beads array (CBA) test. |
| BUN | 1 years | BUN will be tested every three months. |
Countries
China
Outcome results
None listed