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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Type1diabetes
• Intervention / Treatment: Other: Autologous T regulatory cells

Detailed 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

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 14186
    • Karolinska University Hospital
  • Uppsala, Sweden
    • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Autologous Tregs in allogenic islet transplantation; Autologous Tregs are given simultaneously to the patient with the islets	Other: Autologous T regulatory cells; Enriched autologous T regulatory cells are given back to the patient at the time of islet transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Thrombosis	Number of patients with thrombosis in portal veins shown by ultrasound post operative day 1 or later	0-75 days post transplant
Liver function	Number of patients with an elevation of transaminases > 5 times upper normal level during follow up	0-75days
Infections	Number of treatment requiering infections in each patient during follow up	0-90 days post transplantation
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
Immunization	Number of patients with new anti HLA antibodies found at 90 days post transplantation compared to baseline	90 days post transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Insulin independence	Fraction of patients without need of exogeous insulin (ADA criteria) at day 75 post transplantation	day 75
HbA1c	Mean reduction of HbA1c at day 75 compared to baseline(%)	day 75
Hypoglycemic unawareness	Number of patients with a reduced Clarke hypoglycemia awareness score day 75 (+/-5) post transplantation compared to baseline	day 75
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
PRA level	Number of patients with a rise in PRA (panel reactive antibodies) with more than 10% at 90 days post transplantation	day 90

Collaborators and Investigators

• Sponsor: The Nordic Network For Clinical Islet Transplantation
• Investigators: Principal Investigator: Torbjörn Lundgren, MD, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 20, 2018
• Primary Completion (ANTICIPATED): April 30, 2021
• Study Completion (ANTICIPATED): July 31, 2021

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (ACTUAL): March 29, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Transplantation; Islets of Langerhans; T regulatory Cells (autologous)
• 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: AutoTregIsl

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No