Safety and Efficacy Study of Islets Xenotransplantation

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Porcine islets; Other: Autologous Treg

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Cell Transplantation and Gene Therapy Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wei Wang,MD
• Collaborators: Hunan Xeno-life Science Ltd
• Investigators: Study Chair: Wei Wang, PHD,MD, Cell transplantation and gene therapy, the 3rd Xiangya hospital of Central South University

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: January 29, 2014
• First Submitted That Met QC Criteria: May 19, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 29, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Type1 diabetes; xenotransplantation; porcine islets; treg cells; immunosuppress
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CellTransplant&GeneTherapy2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No