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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Level of GLP-1 Receptor (GLP-1R) Gene Expression in PBMCs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Chronic Limb-Threatening Ischemia (CLTI)
A group of patients presenting with chronic limb-threatening ischemia, the most severe form of peripheral artery disease
干预措施: Analysis of GLP-1 receptor expression (Diagnostic Test)
Intermittent claudication (IC)
A group of patients presenting with intermittent claudication, a less advanced stage of of peripheral artery disease, serving as a comparator
干预措施: Analysis of GLP-1 receptor expression (Diagnostic Test)
结局指标
主要结局
Level of GLP-1 Receptor (GLP-1R) Gene Expression in PBMCs
时间窗: Day 1 (at the time of the one-time blood sampling)
Quantification of GLP-1R mRNA expression levels in Peripheral Blood Mononuclear Cells (PBMCs) using RT-qPCR. This measure aims to compare the level of receptor expression between patients with Intermittent Claudication and those with Chronic Limb-Threatening Ischemia.
次要结局
- Systemic Pro-inflammatory Cytokine Profile(Day 1)
- Oxidative and Nitrosative Stress Markers in PBMCs(Day 1)