Arginine-stimulated Prediction of Early Outcome After Islet Transplantation

Study Overview
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Brief Summary
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Through islet transplantation, functional β-cell mass can be restored. Allogeneic islet transplantation is a treatment modality for a select group of patients with complicated type 1 diabetes mellitus. For patients undergoing (partial) pancreas resection, autologous islet transplantation may help prevent complicated diabetes. Up until now, no studies have been performed on early islet graft function in the first week after transplantation. Early graft function may be a predictor for estimating long-term islet graft success. Arginine can excite β-cells to release insulin. It can thus provide an estimate of β-cell secretory capacity and can be used as an alternative to (oral) glucose tolerance tests. In this study, we aim to find a predictor model for islet graft function by assessing peak C-peptide after arginine stimulus in the early post-transplantation phase.

Official Title
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Arginine-stimulated Prediction of Early Outcome After Islet Transplantation

Conditions
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Islets of Langerhans Transplantation, Diabetes Mellitus, Chronic Pancreatitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16 years or older Currently on the LUMC waiting list for allogeneic or autologous islet transplantation Willing to use a flash glucose monitoring (FGM) system in the two weeks prior to transplantation Exclusion Criteria: Patients who are pregnant Patients with known hypersensitivity to arginine

Ages Eligible for Study
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Minimum Age: 16 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Autologous islet transplantation<br>Arginine stimulation test: 5 grams of arginine hydrochloride intravenously. Performed at baseline after mixed meal tolerance test (MMTT), performed separately at day -1 or 0, day 1, day 3, day 7 and 3 months, and also at 3 months after MMTT. | |
| Allogeneic islet transplantation<br>Arginine stimulation test: 5 grams of arginine hydrochloride intravenously. Performed at day -1 or 0, day 1, day 3, day 7, 3 months and at 3 months after MMTT. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early islet graft function | Peak C-peptide during AST at day 3 | Day 3 | 
| Early islet graft function | AUC C-peptide during MMTT at 3 months | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early islet graft function | Peak C-peptide during AST and MMTT (other than primary) | Up to 3 months | 
| Early islet graft function | AUC C-peptide during AST and MMTT (other than primary) | Up to 3 months | 
| Insulin secretory capacity | Relationship between in vitro secretion and in vivo secretion | Up to 3 months | 
| Beta-cell death | Circulating free INS DNA (INS cfDNA) | Up to 3 months | 
| Beta-cell death | insulin - proinsulin ratio | Up to 3 months | 
| Beta-cell death | Plasma circulating microRNA | Up to 3 months | 
| Complement factors | Markers of complement activation | Up to 3 months | 
| Immunological markers | Peripheral blood mononuclear cell (PBMC) composition | Up to 3 months | 
| Immunological markers | T-cell phenotyping | Up to 3 months | 
| Beta cell graft function | Time in range, time below range, time above range as measured by Flash Glucose Monitoring (FGM) or Continuous Glucose Monitoring (CGM) | Up to 3 months | 
| Beta cell graft function | assessed by Igls 2.0 criteria | 3 months | 
| Treatment success | assessed by Igls 2.0 criteria | 3 months | 
| Beta cell graft function | Amount of severe hypoglycaemic events | Up to 3 months | 
| Beta cell graft function | Insulin requirements (IU/kg/day) | Up to 3 months | 
| Glycemic control | HbA1c (mmol/mol) | Up to 3 months | 
| Coagulation markers | Markers indicative for activation of the coagulation cascade | Up to 3 months | 
| Insulin concentration | Concentration of insulin in the islet product | Before the islet transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ibmir, total pancreatectomy, autologous islet transplantation, TPIAT, beta-cell function, c-peptide, arginine, mixed meal tolerance test, allogeneic islet transplantation, islet function