Safety and Efficacy Study of Islets Xenotransplantation

Study Overview
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Brief Summary
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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.

Official Title
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Investigation of Safety and Efficacy Study of Islets Xenotransplantation for Patients With Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: Porcine islets
* Other: Autologous Treg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Porcine islets and autologous treg<br>Porcine islets:10000 islet equivalent（IEQ）/Kg; Treg:2x10^6/Kg | Other: Porcine islets<br>* 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<br>Other: Autologous Treg<br>* Autologous Treg: 2x10^6/Kg<br>|
| Active Comparator: AutologousTreg<br>Autologous Treg:2x10^6/Kg | Other: Autologous Treg<br>* Autologous Treg: 2x10^6/Kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood glucose | 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Porcine C-peptide | The patient will be detected the porcine C-peptide levels after transplantion every three months. | 1 years | 
| Hemoglobin A1c | After transplantation the patient will be checked hemoglobin A1c every month.The level of HbA1c less than 6.5% was considered as effective. | 1 years | 
| AST | AST will be tested every three months. | 1 years | 
| ALT | ALT will be tested every three months. | 1 years | 
| Scr | Scr will be tested every three months. | 1 years | 
| BUN | BUN will be tested every three months. | 1 years | 
| Ultrasonic examination for liver | Ultrasonic examination will be used for the recipient's liver before transplantation and every three month post transplantation. | 1 years | 
| MRI for liver | MRI will be used for liver before transplantaion and every three month post transplantation. | 1 years | 
| Virus detection | The recipient's serum and peripheral blood monouclear cells (PBMC) will be collected for virus detection every six months. | 2 years | 
| Immune cells detection | The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected for immune cell's analysis. | 1 years | 
| Cytokine detection | The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected cytokine beads array (CBA) test. | 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type1 diabetes, porcine islets, treg cells, immunosuppress, xenotransplantation