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

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

Detailed Description
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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

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

Conditions
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Type1diabetes

Intervention / Treatment
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* Other: Autologous T regulatory cells


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm feasibility and safety study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Tregs in allogenic islet transplantation<br>Autologous Tregs are given simultaneously to the patient with the islets | Other: Autologous T regulatory cells<br>* Enriched autologous T regulatory cells are given back to the patient at the time of islet transplantation<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Islets of Langerhans, T regulatory Cells (autologous), Transplantation