Efficacy of Islet Re-transplantation After Failure of Beta-cell Replacement

Official title

Efficacy and Safety of Islet Re-transplantation After Failure of Beta-cell Replacement

Overview

Islet transplantation and pancreas transplantation are established therapeutic options for selected individuals with type 1 diabetes experiencing severe glycemic instability and recurrent hypoglycemia. Although these approaches significantly improve glycemic management and quality of life, long-term graft survival remains limited, with a progressive decline in beta-cell function over time. The clinical benefit-risk profile of islet re-transplantation after graft failure remains poorly defined, and outcomes following repeat islet transplantation after prior islet graft failure have not been specifically evaluated. Repeated exposure to multiple donors may increase the risk of alloimmunization, including the development of donor-specific antibodies , which may adversely affect graft survival and limit access to future transplantation. This multicenter retrospective cohort study aims to evaluate the efficacy and safety of islet re-transplantation in adults with type 1 diabetes after failure of initial beta-cell replacement (islet or pancreas transplantation), with outcomes assessed at 3 months, 1 year, and 5 years.

Primary outcome measures

• Islet graft success [Time frame: Baseline, 3 months, 1 year, 5 years]

Secondary outcome measures (12)

• Glycemic Control_Glycated hemoglobin (HbA1c) level [Time frame: Baseline, 3 months, 1 year, 5 years]
• Glycemic Control_Percentage of individuals with HbA1c < 7% and no severe hypoglycemia [Time frame: Baseline, 3 months, 12 months, 5 years]
• Beta-Cell Function_BETA-2 score [Time frame: Baseline, 3 months, 1 year, 5 years]
• Beta-Cell Function_BETA score [Time frame: Baseline, 3 months, 1 year, 5 years]
• Beta-Cell Function_Severe hypoglycemia events [Time frame: Baseline, 3 months, 1 year, 5 years]
• Beta-Cell Function_Residual beta cell function [Time frame: Baseline, 3 months, 1 year, 5 years]
• Immunological Outcomes_Donor-specific antibodies (DSA) [Time frame: Baseline, 3 months, 1 year, 5 years]
• Immunological Outcomes_Autoantibodies [Time frame: Baseline, 3 months, 1 year, 5 years]
• Safety of islet re-transplantation_Procedural complications of islet infusions [Time frame: Baseline, 3 months, 1 year, 5 years]
• Safety of islet re-transplantation_Renal function eGFR [Time frame: Baseline, 3 months, 1 year, 5 years]
• Safety of islet re-transplantation_Albuminuria [Time frame: Baseline, 3 months, 1 year, 5 years]
• Safety of islet re-transplantation_Immunosuppression-related complications [Time frame: 3 months, 1 year, 5 years]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Diagnosis of type 1 diabetes
• Prior beta-cell replacement therapy : islet transplantation or pancreas transplantation
• Islet re-transplantation performed after 2005
• Islet re-transplantation performed after documented beta cell graft failure, defined by undetectable C-peptide and/or recurrence of severe hypoglycemia on insulin therapy
• Availability of clinical and biological data required for assessment of study outcomes

Exclusion criteria

• Missing or incomplete data preventing assessment of the primary outcome
• Patients who did not meet inclusion criteria

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 1 center

• Montpellier University Hospital — Montpellier

Publications

• Chetboun M, Drumez E, Ballou C, Maanaoui M, Payne E, Barton F, Kerr-Conte J, Vantyghem MC, Piemonti L, Rickels MR, Labreuche J, Pattou F; Collaborative Islet Transplant Registry (CITR) Investigators study group. Association between primary graft function and 5-year outcomes of islet allogeneic transplantation in type 1 diabetes: a retrospective, multicentre, observational cohort study in 1210 pati PMID 37105208
• Maanaoui M, Chetboun M, Top I, Elsermans V, Kerr-Conte J, Le Mapihan K, Defrance F, Gmyr V, Hubert T, Labalette M, Hazzan M, Vantyghem MC, Pattou F. The challenge of HLA donor specific antibodies in the management of pancreatic islet transplantation: an illustrative case-series. Sci Rep. 2022 Jul 21;12(1):12463. doi: 10.1038/s41598-022-16782-3. PMID 35864198
• Wojtusciszyn A, Branchereau J, Esposito L, Badet L, Buron F, Chetboun M, Kessler L, Morelon E, Berney T, Pattou F, Benhamou PY, Vantyghem MC; TREPID group. Indications for islet or pancreatic transplantation: Statement of the TREPID working group on behalf of the Societe francophone du diabete (SFD), Societe francaise d'endocrinologie (SFE), Societe francophone de transplantation (SFT) and Societe PMID 30223084
• Rickels MR, Stock PG, de Koning EJP, Piemonti L, Pratschke J, Alejandro R, Bellin MD, Berney T, Choudhary P, Johnson PR, Kandaswamy R, Kay TWH, Keymeulen B, Kudva YC, Latres E, Langer RM, Lehmann R, Ludwig B, Markmann JF, Marinac M, Odorico JS, Pattou F, Senior PA, Shaw JAM, Vantyghem MC, White S. Defining Outcomes for beta-cell Replacement Therapy in the Treatment of Diabetes: A Consensus Report PMID 29528967

Identifiers

NCT: NCT07666789 · 2025-06-290 · A111/2025-06-290/001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗