Arginine-stimulated Indication of Early Outcome After Islet Transplantation (ALADDIN)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus; Islets of Langerhans Transplantation; Chronic Pancreatitis

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333ZA
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients receiving allogeneic or autologous islet transplants.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: Prof. Eelco de Koning, LUMC

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: September 9, 2022
• First Submitted That Met QC Criteria: September 9, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: arginine; beta-cell function; c-peptide; total pancreatectomy; autologous islet transplantation; TPIAT; mixed meal tolerance test; allogeneic islet transplantation; islet function; ibmir
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Pancreatic Diseases; Chronic Disease; Pancreatitis; Pancreatitis, Chronic
• Other Study ID Numbers: NL79536.058.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No