ALADDIN: Arginine-stimulated Prediction of Early Outcome After Islet Transplantation

Sponsor

Leiden University Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05540197

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Islets of Langerhans Transplantation Diabetes Mellitus Chronic Pancreatitis

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Arginine-stimulated Prediction of Early Outcome After Islet Transplantation

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Autologous islet transplantation 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 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.

Outcome Measures

Primary Outcome Measures

Early islet graft function [Day 3]
Peak C-peptide during AST at day 3
Early islet graft function [Month 3]
AUC C-peptide during MMTT at 3 months

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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