Safety and Efficacy Study of Islets Xenotransplantation
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Porcine islets
Autologous Treg
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Type1 diabetes, porcine islets, treg cells, immunosuppress, xenotransplantation
Eligibility Criteria
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
Sites / Locations
- Cell Transplantation and Gene Therapy Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Porcine islets and autologous treg
AutologousTreg
Arm Description
Porcine islets:10000 islet equivalent(IEQ)/Kg; Treg:2x10^6/Kg
Autologous Treg:2x10^6/Kg
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Porcine C-peptide
The patient will be detected the porcine C-peptide levels after transplantion every three months.
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.
AST
AST will be tested every three months.
ALT
ALT will be tested every three months.
Scr
Scr will be tested every three months.
BUN
BUN will be tested every three months.
Ultrasonic examination for liver
Ultrasonic examination will be used for the recipient's liver before transplantation and every three month post transplantation.
MRI for liver
MRI will be used for liver before transplantaion and every three month post transplantation.
Virus detection
The recipient's serum and peripheral blood monouclear cells (PBMC) will be collected for virus detection every six months.
Immune cells detection
The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected for immune cell's analysis.
Cytokine detection
The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected cytokine beads array (CBA) test.
Full Information
NCT ID
NCT03162237
First Posted
January 29, 2014
Last Updated
May 29, 2020
Sponsor
Wei Wang,MD
Collaborators
Hunan Xeno-life Science Ltd
1. Study Identification
Unique Protocol Identification Number
NCT03162237
Brief Title
Safety and Efficacy Study of Islets Xenotransplantation
Official Title
Investigation of Safety and Efficacy Study of Islets Xenotransplantation for Patients With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Wei Wang,MD
Collaborators
Hunan Xeno-life Science Ltd
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Type1 diabetes, porcine islets, treg cells, immunosuppress, xenotransplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Porcine islets and autologous treg
Arm Type
Experimental
Arm Description
Porcine islets:10000 islet equivalent(IEQ)/Kg; Treg:2x10^6/Kg
Arm Title
AutologousTreg
Arm Type
Active Comparator
Arm Description
Autologous Treg:2x10^6/Kg
Intervention Type
Other
Intervention Name(s)
Porcine islets
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Autologous Treg
Intervention Description
Autologous Treg: 2x10^6/Kg
Primary Outcome Measure Information:
Title
Blood glucose
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Porcine C-peptide
Description
The patient will be detected the porcine C-peptide levels after transplantion every three months.
Time Frame
1 years
Title
Hemoglobin A1c
Description
After transplantation the patient will be checked hemoglobin A1c every month.The level of HbA1c less than 6.5% was considered as effective.
Time Frame
1 years
Title
AST
Description
AST will be tested every three months.
Time Frame
1 years
Title
ALT
Description
ALT will be tested every three months.
Time Frame
1 years
Title
Scr
Description
Scr will be tested every three months.
Time Frame
1 years
Title
BUN
Description
BUN will be tested every three months.
Time Frame
1 years
Title
Ultrasonic examination for liver
Description
Ultrasonic examination will be used for the recipient's liver before transplantation and every three month post transplantation.
Time Frame
1 years
Title
MRI for liver
Description
MRI will be used for liver before transplantaion and every three month post transplantation.
Time Frame
1 years
Title
Virus detection
Description
The recipient's serum and peripheral blood monouclear cells (PBMC) will be collected for virus detection every six months.
Time Frame
2 years
Title
Immune cells detection
Description
The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected for immune cell's analysis.
Time Frame
1 years
Title
Cytokine detection
Description
The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected cytokine beads array (CBA) test.
Time Frame
1 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Wang, PHD,MD
Organizational Affiliation
Cell transplantation and gene therapy, the 3rd Xiangya hospital of Central South University
Official's Role
Study Chair
Facility Information:
Facility Name
Cell Transplantation and Gene Therapy Institute
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Efficacy Study of Islets Xenotransplantation
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