Safety and Efficacy Study of Islets Xenotransplantation

Sponsor

Wei Wang,MD (Other)

Overall Status

Completed

CT.gov ID

NCT03162237

Collaborator

Hunan Xeno-life Science Ltd (Other)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Other: Porcine islets Other: Autologous Treg	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2013

Actual Primary Completion Date :

Dec 1, 2018

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Porcine islets and autologous treg Porcine islets:10000 islet equivalent（IEQ）/Kg; Treg:2x10^6/Kg	Other: Porcine 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 Other: Autologous Treg Autologous Treg: 2x10^6/Kg
Active Comparator: AutologousTreg Autologous Treg:2x10^6/Kg	Other: Autologous Treg Autologous Treg: 2x10^6/Kg

Arm

Intervention/Treatment

Experimental: Porcine islets and autologous treg

Porcine islets:10000 islet equivalent（IEQ）/Kg; Treg:2x10^6/Kg

Other: Porcine 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

Other: Autologous Treg

Autologous Treg: 2x10^6/Kg

Active Comparator: AutologousTreg

Autologous Treg:2x10^6/Kg

Other: Autologous Treg

Autologous Treg: 2x10^6/Kg

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
BUN [1 years]
BUN will be tested every three 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.
Virus detection [2 years]
The recipient's serum and peripheral blood monouclear cells (PBMC) will be collected for virus detection every six months.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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