Expression of GLP1 Receptor on Peripheral Blood Mononuclear Cells in Advanced Peripheral Artery Disease: Paving the Way for GLP1R Agonists Treatment in Chronic Limb Threatening Ischemia
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Analysis of GLP-1 receptor expression.
- Who it may be relevant to
- Registry conditions: Peripheral Arterial Disease (PAD), Claudication, Intermittent, Chronic Limb-Threatening Ischemia. Basic parameters: from 40 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
The goal of this observational study is to learn whether activation of the GLP-1 receptor could represent a therapeutic target by characterizing its expression and associated inflammatory mechanisms in patients with peripheral artery disease, according to disease severity, in adults with symptomatic lower-limb peripheral arterial disease. The main questions it aims to answer are: * Is the level of GLP-1 receptor (GLP1R) expression on peripheral blood mononuclear cells (PBMC) different between patients with intermittent claudication (ischemia of effort) and those with chronic limb-threatening ischemia? * Is GLP1R expression associated with inflammatory and oxidative profiles of PBMC? * Can GLP-1 receptor agonists reverse inflammatory and oxidative alterations induced by plasma from patients with peripheral artery disease in endothelial cell cultures? * Are there specific plasma proteomic signatures associated with GLP1R overexpression? Researchers will compare patients with intermittent claudication to patients with chronic limb-threatening ischemia to see if disease severity is associated with differences in GLP1R expression, PBMC inflammatory/oxidative phenotype, and plasma proteomic profiles. Participants will: * Provide an additional blood sample (15 mL) collected during a routine, clinically indicated blood draw * Have PBMC isolated for measurement of GLP1R expression and assessment of inflammatory and oxidative markers * Have plasma analyzed for proteomic profiling and used in in-vitro endothelial cell experiments Participation ends after completion of the blood sampling, and no additional procedures beyond standard clinical care are required.
Detailed description
Chronic limb-threatening ischemia is the most severe stage of lower-limb peripheral arterial disease and remains associated with poor cardiovascular and limb prognosis. This condition is characterized by a pronounced systemic inflammatory and oxidative state, in which peripheral blood mononuclear cells play a central role.
Glucagon-like peptide-1 receptor agonists have shown anti-inflammatory and cardiovascular protective effects in other settings, but the involvement of the GLP-1 receptor in severe peripheral arterial disease has not been clearly established. This pilot study aims to characterize GLP-1 receptor expression on peripheral blood mononuclear cells according to disease severity and to evaluate its association with inflammatory, oxidative, and proteomic profiles.
This is a monocentric, cross-sectional observational study conducted at the CHU of Strasbourg. Patients hospitalized for evaluation of symptomatic lower-limb peripheral arterial disease will be classified into intermittent claudication or chronic limb-threatening ischemia groups. A single additional blood sample will be collected during routine clinical sampling. Peripheral blood mononuclear cells and plasma will be analyzed to assess GLP-1 receptor expression, inflammatory and oxidative markers, and plasma proteomic signatures. Exploratory in-vitro experiments will evaluate the ability of GLP-1 receptor agonists to reverse endothelial alterations induced by patient plasma.
The study is designed to generate mechanistic data supporting the GLP-1 receptor as a potential therapeutic target in chronic limb-threatening ischemia and to inform future interventional studies.
Interventions
- Diagnostic test Analysis of GLP-1 receptor expression
One-time 15mL blood sampling for GLP-1R expression analysis on PBMCs via RT-qPCR and Western blot
Primary outcome measures
- Level of GLP-1 Receptor (GLP-1R) Gene Expression in PBMCs [Time frame: Day 1 (at the time of the one-time blood sampling)]
Secondary outcome measures (2)
- Systemic Pro-inflammatory Cytokine Profile [Time frame: Day 1]
- Oxidative and Nitrosative Stress Markers in PBMCs [Time frame: Day 1]
Eligibility criteria
Inclusion criteria
- Patients aged 40 years or older
- Documented Peripheral Artery Disease (PAD): Patients must fall into one of the two following severity groups:
- Intermittent Claudication (IC) Group: Defined by a maximum walking distance limited by intermittent claudication, associated with an Ankle-Brachial Index (ABI) < 0.9 at rest.
- Chronic Limb-Threatening Ischemia (CLTI) Group: Defined by ischemic rest pain and/or tissue loss (ulcers or gangrene) persisting for at least 15 days, associated with a toe pressure or a transcutaneous oxygen tension (tcPO2) < 30 mmHg, according to the 2024 ESC guidelines.
Exclusion criteria
- Diabetes Mellitus: Diagnosis of Type 1 or Type 2 diabetes
- Current Specific Pharmacotherapy: Ongoing treatment with SGLT2 inhibitors (SGLT2i) or GLP-1 receptor agonists (GLP-1RA).
- Infection: Presence of sepsis or an active systemic infection.
- Malignancy: Active cancer or hematologic malignancies.
- Immunosuppression: History of organ transplantation or autoimmune diseases currently requiring immunosuppressive therapy.
- Known chronic inflammatory diseases.
- Advanced Renal Failure: End-stage renal disease requiring dialysis.
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
- Case-control
Study locations
France · 1 center
- Hôpitaux Universitaires de Strasbourg — Strasbourg
Identifiers
NCT: NCT07340112 · 9908