Extracellular Vesicle-based Strategy to Stratify Islets and Improve Their FItness Before Transplantation

NCT07812974 | Not Yet Recruiting

• 1 other identifier: 9904
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Islet transplantation restores glucose tolerance in people living with diabetes characterised by high glycaemic variability: 90 per cent of patients were free from severe hypoglycaemia at 5 years, compared with 26 per cent prior to transplantation, and 50 per cent of patients were insulin-independent at 1 year. However, follow-up of participants is characterised by a gradual loss of islet function, with only 30 per cent of patients remaining insulin-independent at 5 years. The greatest limitation and challenge of islet transplantation lies in the substantial loss of islet mass infused via the portal vein at the start of the post-transplant period. Up to 50 per cent of the graft may be lost in the days following transplantation. This early loss is due to a combination of stress and non-specific inflammatory and immune mechanisms, as well as blood-mediated inflammatory reactions, which compromise the survival, engraftment, revascularisation and early function of the transplanted islets. Consequently, multiple islet infusions are often required to achieve satisfactory metabolic outcomes in recipients. However, due to the scarcity of available donors, the widespread application of islet transplantation remains limited as a result. During the culture period, cells in the islet preparation release extracellular vesicles (EVs) - either secreted by the plasma membrane (microvesicles, MVs) or of intracellular endosomal origin (exosomes) - which play a major role in intercellular communication. Microvesicles carry various markers and effectors that can render them either harmful (pro-coagulant, pro-apoptotic, pro-inflammatory and pro-senescent) or protective. We therefore hypothesise that (1) EVs released during the preparation of islets prior to transplantation (hereinafter referred to as Graft-EVs) reflect the quality of the pancreatic islets, (2) certain EVs have a protective or deleterious effect on the pancreatic islet, and (3) reconditioning the islets by enriching them with protective EVs improved graft quality under the pro-inflammatory conditions of IBMIR. We therefore propose to develop an EV-based islet preconditioning strategy to improve graft survival and function.

Conditions

Type 1 Diabetes (T1D)

Outcome Measures

Primary Outcomes (2)

• Primary function of the graft measured one month after the last islet injection (beta2score)

  1 month after the last islet injection

• Using the criteria for graft success (IGLS score)

  one and two years post-transplant in recipients

Study Arms (1)

Patient with type 1 diabetes on the waiting list for a pancreatic islet transplant

Other: beta2score

Interventions

beta2score OTHER

The BETA-2 score enables the detection of insulin independence following islet transplantation (BETA-2 score \< 20) with a specificity and sensitivity of over 82 per cent.

Patient with type 1 diabetes on the waiting list for a pancreatic islet transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with type 1 diabetes

You may qualify if:

• Adult patients with no upper age limit
• Men or women
• Patients with type 1 diabetes
• Patients on the waiting list for a pancreatic islet transplant (Agence de Biomédecine)
• Patients who have given their consent for their data to be reused for the purposes of this research

You may not qualify if:

• Pregnant women
• Patients under guardianship or administration
• Individuals subject to judicial protection measures

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Hôpitaux universitaires de Strasbourg

Strasbourg, 67200, France

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Laurent MEYER

  Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cécile Arnold

CONTACT

0033 3 88 11 51 48; cecile.arnold@chru-strasbourg.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 10, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): January 1, 2032
• Last Updated: September 10, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)