Diabetes Mellitus
Conditions
Brief summary
This is a dual centre, single arm, exploratory study of the possibility to use eculizumab (Soliris) to prevent/reduce destruction of islets of Langerhans after portal infusion of the islets in patients with diabetics accepted for islet transplant.
Detailed description
This is a dual centre, single arm, exploratory study of the possibility to use eculizumab (Soliris) to prevent/reduce destruction of islets of Langerhans after portal infusion of the islets in patients with diabetics accepted for islet transplant. Ten patients from 2 centres (Uppsala University Hospital and Karolinska University Hospital in Stockholm) will be transplanted. The purpose of the study is to investigate if selective complement inhibition by eculizumab combined with standard anticoagulation during and after transplantation can further reduce the extent of early tissue loss after portal infusion of islets.
Interventions
DRUGEculizumab
Intravenous infusion (1200 mg) over 35 minutes. Consecutive infusions (900 mg) on Days 1, 7 and 14.
Sponsors
Uppsala University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients between 18 to 65 years of age * Patients able to provide written informed consent * Absent stimulated c-peptide (\< 0.1 nmol/L). This includes also previously islet-transplanted patients with no detectable c-peptide. * Patients at fear of severe hypoglycemia * Female patients of child bearing potential must have a negative pregnancy test (s-β-HCG) and must be practicing an effective, reliable medical accepted contraceptive regimen while on eculizumab treatment and to study end at 75 days. * Patients vaccinated against Neisseria meningitides or patients accepting adequate antibiotic prophylaxis
Exclusion criteria
* Body mass index \> 30 kg/m2 * Untreated proliferative diabetes retinopathy * Recipient of any other concomitant organ transplantation - Glomerular filtration rate \< 50 mL/min before first islet transplantation * Positive T-cell cross-matching by Complement Depending Cytotoxicity (CDC) * Pregnancy or lactating * Active ongoing infection, bacterial or viral * Unresolved meningococcal disease * Known bleeding disorder * Known complement disorder * Have received any other investigational drug within 30 days before inclusion * History of drug or alcohol abuse within the last year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Increased survival of ICC´s transplanted as measured by peak c-peptide | During and within two hours post infusion (day 0). | Determined by PET-scan of 2-deoxy-27fluoro-D-glucose (18F) (FDG)-labelled islets infused in the portal vein. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monitoring of islet-function and survival. | 14, 30 and 75 days post-transplant. | Evaluation of insulin-independency, the extent of reduction of baseline insulin requirement, continuous glucose monitoring system (CGMS) performance, HbA1c, number of hypoglycemic events per week. |
| Adverse events (AEs) and serious adverse events (SAEs) | From start of infusion until 75 days post-transplant. | Will be assigned Medical Drug Regulatory Activities (MedDRA) preferred terms and tabulated as incidence rate |
| Patient and graft survival at 75 days post treatment. | From start of infusion until 75 days post-transplant. | Graft survival is measured by measurable stimulated c-peptide (\>0,1 nmol/L) |
| Estimated glomerular filtration rate (GFR) (Cystatin C) | At day 75 | Cystatin C value |
| Portal vein thrombosis | The day after infusion | Assessment by per protocol ultrasound |
| Bleeding | From infusion until 2 hours post start of infusion | will be assessed by hemoglobin and thrombocyte monitoring (important while portal vein catheter is in place and withdrawn (within first week). |
| Effect of eculizumab on instant blood mediated inflammatory reaction (IBMIR) as determined by complement activation. | At the end of infusion and 1 and 2 h post start of infusion (day 0). | Extent of early tissue loss |
Other
| Measure | Time frame | Description |
|---|---|---|
| The percentage of loss of radioactivity in the liver field. | Within the first two hours after start of islet infusion. | When logistically feasible. Determined by positron emission tomography (PET)-scan of 2-deoxy-27fluoro-D-glucose ((18F) (FDG)-labelled islets infused in the portal vein as assessed during treatment (only possible at the Uppsala site). |
| Effect of eculizumab on IBMIR | Post infusion | Determined by coagulation activation (TAT) |
Countries
Sweden
Outcome results
None listed