Infusion of Autologous T Regulatory Cells (T Reg) at the Time of Transplantation of Allogenic Islets of Langerhans
Primary Purpose
Type1diabetes
Status
Unknown status
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Autologous T regulatory cells
Sponsored by
About this trial
This is an interventional treatment trial for Type1diabetes focused on measuring Transplantation, Islets of Langerhans, T regulatory Cells (autologous)
Eligibility Criteria
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
Sites / Locations
- Karolinska University Hospital
- Uppsala University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Autologous Tregs in allogenic islet transplantation
Arm Description
Autologous Tregs are given simultaneously to the patient with the islets
Outcomes
Primary Outcome Measures
Bleeding
Number of patients with >20g/L reduction of haemoglobine and signs of bleeding shown by ultrasound post operative day 1
Thrombosis
Number of patients with thrombosis in portal veins shown by ultrasound post operative day 1 or later
Liver function
Number of patients with an elevation of transaminases > 5 times upper normal level during follow up
Infections
Number of treatment requiering infections in each patient during follow up
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.
Immunization
Number of patients with new anti HLA antibodies found at 90 days post transplantation compared to baseline
Secondary Outcome Measures
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
Insulin independence
Fraction of patients without need of exogeous insulin (ADA criteria) at day 75 post transplantation
HbA1c
Mean reduction of HbA1c at day 75 compared to baseline(%)
Hypoglycemic unawareness
Number of patients with a reduced Clarke hypoglycemia awareness score day 75 (+/-5) post transplantation compared to baseline
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
PRA level
Number of patients with a rise in PRA (panel reactive antibodies) with more than 10% at 90 days post transplantation
Full Information
NCT ID
NCT04820270
First Posted
March 16, 2021
Last Updated
March 25, 2021
Sponsor
The Nordic Network For Clinical Islet Transplantation
1. Study Identification
Unique Protocol Identification Number
NCT04820270
Brief Title
Infusion of Autologous T Regulatory Cells (T Reg) at the Time of Transplantation of Allogenic Islets of Langerhans
Official Title
Infusion of Autologous T Regulatory Cells (T Reg) at the Time of Transplantation of Allogenic Islets of Langerhans
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 20, 2018 (Actual)
Primary Completion Date
April 30, 2021 (Anticipated)
Study Completion Date
July 31, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Nordic Network For Clinical Islet Transplantation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Open single armed study to investigate safety and feasibility of administrating autologous T regulatory cells at the time of allogenic islet transplantation.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1diabetes
Keywords
Transplantation, Islets of Langerhans, T regulatory Cells (autologous)
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Single arm feasibility and safety study
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Autologous Tregs in allogenic islet transplantation
Arm Type
Experimental
Arm Description
Autologous Tregs are given simultaneously to the patient with the islets
Intervention Type
Other
Intervention Name(s)
Autologous T regulatory cells
Intervention Description
Enriched autologous T regulatory cells are given back to the patient at the time of islet transplantation
Primary Outcome Measure Information:
Title
Bleeding
Description
Number of patients with >20g/L reduction of haemoglobine and signs of bleeding shown by ultrasound post operative day 1
Time Frame
0-1 days post transplant
Title
Thrombosis
Description
Number of patients with thrombosis in portal veins shown by ultrasound post operative day 1 or later
Time Frame
0-75 days post transplant
Title
Liver function
Description
Number of patients with an elevation of transaminases > 5 times upper normal level during follow up
Time Frame
0-75days
Title
Infections
Description
Number of treatment requiering infections in each patient during follow up
Time Frame
0-90 days post transplantation
Title
Islet graft failure
Description
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.
Time Frame
day 75
Title
Immunization
Description
Number of patients with new anti HLA antibodies found at 90 days post transplantation compared to baseline
Time Frame
90 days post transplantation
Secondary Outcome Measure Information:
Title
Islet function
Description
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
Time Frame
day 75
Title
Insulin independence
Description
Fraction of patients without need of exogeous insulin (ADA criteria) at day 75 post transplantation
Time Frame
day 75
Title
HbA1c
Description
Mean reduction of HbA1c at day 75 compared to baseline(%)
Time Frame
day 75
Title
Hypoglycemic unawareness
Description
Number of patients with a reduced Clarke hypoglycemia awareness score day 75 (+/-5) post transplantation compared to baseline
Time Frame
day 75
Title
HbA1c and hypoglycemic unawareness combined
Description
Number of patients with both a HbA1c ≤ 6.5% (DCCT) and lack of severe hypoglycemia at day 75 post transplantation
Time Frame
day 75
Title
PRA level
Description
Number of patients with a rise in PRA (panel reactive antibodies) with more than 10% at 90 days post transplantation
Time Frame
day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Torbjörn Lundgren, MD
Organizational Affiliation
Karolinska University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
Country
Sweden
12. IPD Sharing Statement
Learn more about this trial
Infusion of Autologous T Regulatory Cells (T Reg) at the Time of Transplantation of Allogenic Islets of Langerhans
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