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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005421-12 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eculizumab | Experimental | Intravenous infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eculizumab | Drug | Intravenous infusion (1200 mg) over 35 minutes. Consecutive infusions (900 mg) on Days 1, 7 and 14. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Increased survival of ICC´s transplanted as measured by peak c-peptide | Determined by PET-scan of 2-deoxy-27fluoro-D-glucose (18F) (FDG)-labelled islets infused in the portal vein. | During and within two hours post infusion (day 0). |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of eculizumab on instant blood mediated inflammatory reaction (IBMIR) as determined by complement activation. | Extent of early tissue loss | At the end of infusion and 1 and 2 h post start of infusion (day 0). |
| Monitoring of islet-function and survival. |
| Measure | Description | Time Frame |
|---|---|---|
| The percentage of loss of radioactivity in the liver field. | 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). | Within the first two hours after start of islet infusion. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gunnar Tufveson, MD, PhD | Uppsala University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dept of Surgical Sciences, Section of Transplantation Surgery, University Hospital | Uppsala | 752 37 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15983207 | Background | Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes. 2005 Jul;54(7):2060-9. doi: 10.2337/diabetes.54.7.2060. | |
| 17596618 | Background | Eich T, Eriksson O, Lundgren T; Nordic Network for Clinical Islet Transplantation. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. N Engl J Med. 2007 Jun 28;356(26):2754-5. doi: 10.1056/NEJMc070201. No abstract available. |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C481642 | eculizumab |
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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. |
| 14, 30 and 75 days post-transplant. |
| Adverse events (AEs) and serious adverse events (SAEs) | Will be assigned Medical Drug Regulatory Activities (MedDRA) preferred terms and tabulated as incidence rate | From start of infusion until 75 days post-transplant. |
| Patient and graft survival at 75 days post treatment. | Graft survival is measured by measurable stimulated c-peptide (>0,1 nmol/L) | From start of infusion until 75 days post-transplant. |
| Estimated glomerular filtration rate (GFR) (Cystatin C) | Cystatin C value | At day 75 |
| Portal vein thrombosis | Assessment by per protocol ultrasound | The day after infusion |
| Bleeding | will be assessed by hemoglobin and thrombocyte monitoring (important while portal vein catheter is in place and withdrawn (within first week). | From infusion until 2 hours post start of infusion |
| Effect of eculizumab on IBMIR | Determined by coagulation activation (TAT) | Post infusion |
| 17984843 | Background | Eich T, Eriksson O, Sundin A, Estrada S, Brandhorst D, Brandhorst H, Langstrom B, Nilsson B, Korsgren O, Lundgren T. Positron emission tomography: a real-time tool to quantify early islet engraftment in a preclinical large animal model. Transplantation. 2007 Oct 15;84(7):893-8. doi: 10.1097/01.tp.0000284730.86567.9f. |
| 12504401 | Background | Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Kallen R, Ostraat O, Salmela K, Tibell A, Tufveson G, Elgue G, Nilsson Ekdahl K, Korsgren O, Nilsson B. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet. 2002 Dec 21-28;360(9350):2039-45. doi: 10.1016/s0140-6736(02)12020-4. |
| 10512353 | Background | Bennet W, Sundberg B, Groth CG, Brendel MD, Brandhorst D, Brandhorst H, Bretzel RG, Elgue G, Larsson R, Nilsson B, Korsgren O. Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation? Diabetes. 1999 Oct;48(10):1907-14. doi: 10.2337/diabetes.48.10.1907. |
| 20177350 | Background | Koh A, Senior P, Salam A, Kin T, Imes S, Dinyari P, Malcolm A, Toso C, Nilsson B, Korsgren O, Shapiro AM. Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success. Transplantation. 2010 Feb 27;89(4):465-71. doi: 10.1097/TP.0b013e3181c478fd. |
| 19845588 | Background | Eriksson O, Eich T, Sundin A, Tibell A, Tufveson G, Andersson H, Felldin M, Foss A, Kyllonen L, Langstrom B, Nilsson B, Korsgren O, Lundgren T. Positron emission tomography in clinical islet transplantation. Am J Transplant. 2009 Dec;9(12):2816-24. doi: 10.1111/j.1600-6143.2009.02844.x. Epub 2009 Oct 21. |
| 21248660 | Background | Friberg AS, Brandhorst H, Buchwald P, Goto M, Ricordi C, Brandhorst D, Korsgren O. Quantification of the islet product: presentation of a standardized current good manufacturing practices compliant system with minimal variability. Transplantation. 2011 Mar 27;91(6):677-83. doi: 10.1097/TP.0b013e31820ae48e. |