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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

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

18 Years - 40 Years (Adult)All SexesDoes not accept 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

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

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

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

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Safety and Efficacy Study of Islets Xenotransplantation

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