Type1diabetes
Conditions
Keywords
Transplantation, Islets of Langerhans, T regulatory Cells (autologous)
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
Interventions
OTHERAutologous T regulatory cells
Enriched autologous T regulatory cells are given back to the patient at the time of islet transplantation
Sponsors
The Nordic Network For Clinical Islet Transplantation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm feasibility and safety study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunization | 90 days post transplantation | Number of patients with new anti HLA antibodies found at 90 days post transplantation compared to baseline |
| Bleeding | 0-1 days post transplant | Number of patients with \>20g/L reduction of haemoglobine and signs of bleeding shown by ultrasound post operative day 1 |
| Thrombosis | 0-75 days post transplant | Number of patients with thrombosis in portal veins shown by ultrasound post operative day 1 or later |
| Liver function | 0-75days | Number of patients with an elevation of transaminases \> 5 times upper normal level during follow up |
| Infections | 0-90 days post transplantation | Number of treatment requiering infections in each patient during follow up |
| Islet graft failure | day 75 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Islet function | day 75 | 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 | day 75 | Fraction of patients without need of exogeous insulin (ADA criteria) at day 75 post transplantation |
| HbA1c | day 75 | Mean reduction of HbA1c at day 75 compared to baseline(%) |
| Hypoglycemic unawareness | day 75 | Number of patients with a reduced Clarke hypoglycemia awareness score day 75 (+/-5) post transplantation compared to baseline |
| HbA1c and hypoglycemic unawareness combined | day 75 | Number of patients with both a HbA1c ≤ 6.5% (DCCT) and lack of severe hypoglycemia at day 75 post transplantation |
| PRA level | day 90 | Number of patients with a rise in PRA (panel reactive antibodies) with more than 10% at 90 days post transplantation |
Countries
Sweden
Outcome results
None listed