Extracellular Vesicle-based Strategy to Stratify Islets and Improve Their FItness Before Transplantation (EVIFIT)
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Cécile Arnold
- Phone Number: 0033 3 88 11 51 48
- Email: cecile.arnold@chru-strasbourg.fr
Study Locations
-
-
-
Strasbourg, France, 67200
- Hopitaux Universitaires de Strasbourg
-
Contact:
- Laurent MEYER, MD
- Email: laurent.meyer@chru-strasbourg.fr
-
Contact:
- Laurence KESSLER, MD
- Email: kesslerl@unistra.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- Pregnant women
- Patients under guardianship or administration
- Individuals subject to judicial protection measures
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Patient with type 1 diabetes on the waiting list for a pancreatic islet transplant
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Primary function of the graft measured one month after the last islet injection (beta2score)
Time Frame: 1 month after the last islet injection
|
1 month after the last islet injection
|
|
Using the criteria for graft success (IGLS score)
Time Frame: one and two years post-transplant in recipients
|
one and two years post-transplant in recipients
|
Collaborators and Investigators
Investigators
- Principal Investigator: Laurent MEYER, Hopitaux Universitaires de Strasbourg
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 9904
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.