Infusion of Autologous T Regulatory Cells (T Reg) at the Time of Transplantation of Allogenic Islets of Langerhans

Type1diabetes Clinical Trial

Official title:

Infusion of Autologous T Regulatory Cells (T Reg) at the Time of Transplantation of Allogenic Islets of Langerhans

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04820270
• Other study ID #: AutoTregIsl
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 20, 2018
• Est. completion date: July 31, 2021

Study information

• Verified date: March 2021
• Source: The Nordic Network For Clinical Islet Transplantation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open single armed study to investigate safety and feasibility of administrating autologous T regulatory cells at the time of allogenic islet transplantation.

Description:

Open single armed study to investigate safety and feasibility of administrating autologous T regulatory cells at the time of allogenic islet transplantation. Patients are recruited from the waiting list for islet transplantation within The Nordic Network for Clinical Islet Transplantation. Patients included in the study will undergo apheresis while on the waiting list. T regulatory cells will be sorted out and frozen. Autologous, non modified T regs will then be infused simultaneously intraportally with the islet graft at transplantation. Patients will be followed for safety and efficacy regarding the islet transplantation over three months

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 8
• Est. completion date: July 31, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patient must be registered on the waiting list within The Nordic Network for Clinical Islet Transplantation
• Type 1 diabetes with diagnosed <40years of age and with>5 years of exogenous insulin use
• C peptide < 0.1 nmol/L at MMTT if no previous islet transplant
• Adequate previous treatment by an experienced diabetologist
• Patient must understand and be able to sign an informed consent

Exclusion Criteria:

• Patient with a previous transplant other than islets
• Patient with an BMI>30
• Patient with an need of more than 1U/kg of insulin per 24h
• Repeated abnormal liver function tests
• non stable retinopathy
• known abnormalities in coagulation
• known malignancies
• non stable heart conditions
• active infections
• serological proof of hepatitis B or C or HIV
• signs of portal hypertension
• patients that are pregnant, breast feeding or aim to become pregnant during the study period
• patients with a PRA > 20%, positive cross match or known DSA
• patients with conditions that the investigator would consider unsafe to combine with islet transplantation

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type1diabetes

Intervention

Other:
• Autologous T regulatory cells
Enriched autologous T regulatory cells are given back to the patient at the time of islet transplantation

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm
Sweden	Uppsala University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
The Nordic Network For Clinical Islet Transplantation

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bleeding	Number of patients with >20g/L reduction of haemoglobine and signs of bleeding shown by ultrasound post operative day 1	0-1 days post transplant
Primary	Thrombosis	Number of patients with thrombosis in portal veins shown by ultrasound post operative day 1 or later	0-75 days post transplant
Primary	Liver function	Number of patients with an elevation of transaminases > 5 times upper normal level during follow up	0-75days
Primary	Infections	Number of treatment requiering infections in each patient during follow up	0-90 days post transplantation
Primary	Islet graft failure	Number of patients with islet graft failure shown as C peptide <0.1 nmol/L fasting or <0.3 nmol/L (90min) at a MMTT day 75 or lack of improvement compared to baseline if transplanted before.	day 75
Primary	Immunization	Number of patients with new anti HLA antibodies found at 90 days post transplantation compared to baseline	90 days post transplantation
Secondary	Islet function	Fraction of patients with a C-peptide level above 0.1 nmol/L fasting or 0.3 nmol/L (90min) at a MMTT day 75	day 75
Secondary	Insulin independence	Fraction of patients without need of exogeous insulin (ADA criteria) at day 75 post transplantation	day 75
Secondary	HbA1c	Mean reduction of HbA1c at day 75 compared to baseline(%)	day 75
Secondary	Hypoglycemic unawareness	Number of patients with a reduced Clarke hypoglycemia awareness score day 75 (+/-5) post transplantation compared to baseline	day 75
Secondary	HbA1c and hypoglycemic unawareness combined	Number of patients with both a HbA1c = 6.5% (DCCT) and lack of severe hypoglycemia at day 75 post transplantation	day 75
Secondary	PRA level	Number of patients with a rise in PRA (panel reactive antibodies) with more than 10% at 90 days post transplantation	day 90