Efficacy of Islet Re-transplantation After Failure of Beta-cell Replacement (MULT-ILOT)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Islets of Langerhans Transplantation; Type 1 Diabetes (T1D)

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Orianne OV Villard, MD; Phone Number: +33 467 338 382; Email: orianne.villard@chu-montpellier.fr
• Study Contact Backup: Name: Roxane RD Descaillot; Email: roxanedescaillot@gmail.com

Study Locations

• France
  • Montpellier, France, 34000
    • Recruiting
    • Montpellier University Hospital
    • Contact: Orianne OV Villard, MD; Phone Number: +33 467 338 382; Email: orianne.villard@chu-montpellier.fr
    • Principal Investigator: Orianne OV Villard, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adults with type 1 diabetes who underwent prior beta-cell replacement therapy (pancreas or islet transplantation) and subsequent islet re-transplantation after graft failure.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Initial pancreas transplant; Islet after pancreas transplant failure
Initial islet transplant; Islet after islet transplant failure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Islet graft success	Assessed using Igls criteria (optimal or good graft function classification) based on C-peptide, insulin use, hemoglobin A1c, and severe hypoglycemia	Baseline, 3 months, 1 year, 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic Control_Glycated hemoglobin (HbA1c) level	HbA1c level, measured by HPLC method	Baseline, 3 months, 1 year, 5 years
Glycemic Control_Percentage of individuals with HbA1c < 7% and no severe hypoglycemia		Baseline, 3 months, 12 months, 5 years
Beta-Cell Function_BETA-2 score	Derived from fasting glucose, paired fasting C-peptide, insulin dose and Hba1c and generates a single value between 0 and 42	Baseline, 3 months, 1 year, 5 years
Beta-Cell Function_BETA score	Derived from fasting glucose, HbA1c, stimulated C-peptide, and absence of insulin or oral hypoglycemic agent use and generates a single value between 0 and 8	Baseline, 3 months, 1 year, 5 years
Beta-Cell Function_Severe hypoglycemia events	Percentage of individual with severe hypoglycemia events	Baseline, 3 months, 1 year, 5 years
Beta-Cell Function_Residual beta cell function	Percentage of individual with fasting plasma C-peptide > 0.3 ng/mL	Baseline, 3 months, 1 year, 5 years
Immunological Outcomes_Donor-specific antibodies (DSA)	Presence and specificity of donor-specific antibodies (DSA) with classification : Preformed and de novo; Class I and II specificity; and Mean fluorescence intensity (MFI)	Baseline, 3 months, 1 year, 5 years
Immunological Outcomes_Autoantibodies	Dosage of antibodies anti-GAD, anti-IA2, anti-insulin, and anti-ZnT8	Baseline, 3 months, 1 year, 5 years
Safety of islet re-transplantation_Procedural complications of islet infusions	Reported of procedural complications of islet infusions such as portal thrombosis, hematoma, transfusion requirement	Baseline, 3 months, 1 year, 5 years
Safety of islet re-transplantation_Renal function eGFR	Estimated GFR from serum creatinine level	Baseline, 3 months, 1 year, 5 years
Safety of islet re-transplantation_Albuminuria	Measurement of albuminuria or proteinuria	Baseline, 3 months, 1 year, 5 years
Safety of islet re-transplantation_Immunosuppression-related complications	Reported immunosuppression-related complications such as infections ; malignancy, cardiovascular events	3 months, 1 year, 5 years
Safety of islet re-transplantation_Mortality	Patient death	3 months, 1 year, 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic control_Time in range (70-180 mg/dL)	Continuous Glucose Monitoring (CGM) measured time with glucose between 70 and 180 mg/dL	Baseline, 3 months, 1 year and 5 years
Glycemic control_Time in tight range (70-140 mg/dL)	Continuous Glucose Monitoring (CGM) measured time with glucose between 70 and 140 mg/dL	Baseline, 3 months, 1 year and 5 years
Glycemic control_Time below range 70 mg/dL	Continuous Glucose Monitoring (CGM) measured time with glucose between 70 and 54 mg/dL	Baseline, 3 months, 1 year and 5 years
Glycemic control_Time below range 54 mg/dL	Continuous Glucose Monitoring (CGM) measured time with glucose below 54 mg/dL	Baseline, 3 months, 1 year and 5 years
Glycemic control_Time above range 180 mg/dL	Continuous Glucose Monitoring (CGM) measured time with glucose between 180 and 250 mg/dL	Baseline, 3 months, 1 year and 5 years
Glycemic control_Time above range 250 mg/dL	Continuous Glucose Monitoring (CGM) measured time with glucose above 250 mg/dL	Baseline, 3 months, 1 year and 5 years
Glycemic control_Mean glucose	Continuous Glucose Monitoring (CGM) derived-metrics	Baseline, 3 months, 1 year and 5 years
Glycemic control_Coefficient of variation	Continuous Glucose Monitoring (CGM) derived-metrics	Baseline, 3 months, 1 year and 5 years
Glycemic control_Glycemic risk index	Continuous Glucose Monitoring (CGM) derived-metrics	Baseline, 3 months, 1 year and 5 years
Glycemic control_Glucose Management Indicator (GMI)	Continuous Glucose Monitoring (CGM) derived-metrics	Baseline, 3 months, 1 year and 5 years

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: University Hospital, Grenoble; University Hospital, Toulouse; University Hospital, Lille; University Hospital, Paris; University Hospital, Strasbourg; The Civil Hospitals, Lyon

Publications and helpful links

General 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 patients from the Collaborative Islet Transplant Registry. Lancet Diabetes Endocrinol. 2023 Jun;11(6):391-401. doi: 10.1016/S2213-8587(23)00082-7. Epub 2023 Apr 24.
• 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.
• 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 francaise de nephrologie - dialyse - transplantation (SFNDT). Diabetes Metab. 2019 Jun;45(3):224-237. doi: 10.1016/j.diabet.2018.07.006. Epub 2018 Sep 14.
• 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 on the Igls Criteria From the IPITA/EPITA Opinion Leaders Workshop. Transplantation. 2018 Sep;102(9):1479-1486. doi: 10.1097/TP.0000000000002158.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 21, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 21, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: islet transplantation; type 1 diabetes; beta cell replacement; glycemic control; graft survival; pancreas transplantation
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2025-06-290; A111/2025-06-290/001 (Other Identifier: Scientific and ethics committee of the Montpellier University Hospital)

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 device product: No