Safety and Efficacy Study of Islets Xenotransplantation

Not Applicable

Completed

• Conditions: Type 1 Diabetes
• Interventions: Other: Porcine islets; Other: Autologous Treg

• Registration Number: NCT03162237
• Lead Sponsor: Wei Wang,MD

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07
• Study First Submitted: 2014-01-29
• Study First Submitted QC: 2017-05-19
• Study First Posted: 2017-05-22
• Primary Completion: 2018-12
• Study Completion: 2018-12
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-29
• Last Update Posted: 2020-06-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Porcine islets and autologous treg	Porcine islets	Porcine islets:10000 islet equivalent（IEQ）/Kg; Treg:2x10\^6/Kg
Porcine islets and autologous treg	Autologous Treg	Porcine islets:10000 islet equivalent（IEQ）/Kg; Treg:2x10\^6/Kg
AutologousTreg	Autologous Treg	Autologous Treg:2x10\^6/Kg

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Scr	1 years	Scr will be tested every three months.
Cytokine detection	1 years	The recipient's peripheral blood monouclear cells (PBMC) and the serum will be collected cytokine beads array (CBA) test.
ALT	1 years	ALT will be tested every three months.
BUN	1 years	BUN will be tested every three months.
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.
Ultrasonic examination for liver	1 years	Ultrasonic examination will be used for the recipient's liver before transplantation 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.

Trial Locations

Locations (1)

Cell Transplantation and Gene Therapy Institute; 🇨🇳 Changsha, Hunan, China