Impact of GLP1-RAs on Inflammation and Endothelial biomarkerS in Type 2 diABetes meLlitus patiEnts: STABLE-GLP1 Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- To evaluate the effects of semaglutide in addition to standard therapy on inflammatory biomarkers compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.
研究概览
简要总结
Type II diabetes mellitus (T2DM) is a chronic disease associated with a very high risk of developing cardiovascular (CV) events, especially because of its long-term effects. Glucagon-like-peptide-1 receptor agonists (GLP1-RAs) are recommended in subjects suffering from T2DM with a history or at risk for CV disease; however there is a lack of evidence on local actions of GLP1-RAs on inflammation and endothelial function.
The STABLE-GLP1 study aims to evaluate, in patients with T2DM without atherosclerotic cardiovascular disease (ASCVD) or severe target-organ damage (TOD), the possible beneficial effect of semaglutide, a GLP1-AR, on clinical prognosis, inflammatory and endothelial biomarkers.
The STABLE-GLP1 trial is a phase IV interventional, national, multicenter, randomized, pragmatic study, aiming at enrolling 80 patients with T2DM and no ASCVD. Participants will be randomized in 1:1 ratio to receive semaglutide in addition to standard therapy or standard therapy alone, according to body mass index (BMI) category (BMI <30 vs. ≥30 kg/m²). All patients will perform clinical visit, ECG, echocardiography, blood sample collection for endothelial and inflammatory biomarkers dosage at baseline, at 26 weeks, and after 52 weeks of treatment. Data from CTA, performed according to clinical practice before enrollment, will be recorded and retrospectively evaluated to test secondary outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Endpoint assessment and statistical analysis will be performed by personnel blinded to treatment assignment to reduce the risk of bias in data interpretation. In addition, the Events Adjudication Committee will be composed of at least three board-certified cardiologists, who are not involved in the conduct of the trial and are blinded to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Diagnosis of T2DM in patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10% with clinical indication in accordance with current guidelines [1] to initiate semaglutide therapy (level of evidence IIa).
- •Evaluable, pre-randomization CTA with no evidence of stenosis ≥50% of epicardial coronary vessels, as confirmed by the core laboratory, performed within 2 years prior to inclusion.
- •Stable clinical conditions, with controlled blood pressure, lipid profile, and glycemic values, based on assessments performed within 4 weeks prior to inclusion.
- •Stable antidiabetic treatment for at least 6 weeks.
- •Left ventricular ejection fraction ≥50%.
- •For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential, confirmed at enrollment by one of the following:
- •(a) Postmenopausal, defined as amenorrhea for ≥12 months following cessation of fall exogenous hormonal treatments, and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range. (b) Documentation of irreversible surgical sterilization by hysterectomy bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization.
- •Ability to understand study procedures and sign informed consent.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Age > 85 years.
- •Previous treatment with semaglutide or GLP1-RAs.
- •Patients with stenosis of epicardial coronary arteries ≥50%.
- •eGFR <45 mL/min/1.73 m2 irrespective of albuminuria or eGFR 45-59 mL/min/1.73 m2 and microalbuminuria (UACR 30-300 mg/g; stage A2) or proteinuria (UACR >300 mg/g; stage A3) or presence of microvascular disease in at least three different sites [e.g. microalbuminuria (stage A2) plus retinopathy plus neuropathy], based on assessments performed within 4 weeks prior to inclusion.
- •History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
- •Any history of ASCVD.
- •Ongoing New York Heart Association Class IV (heart failure (HF).
- •Significant valvulopathy.
- •Type 1 diabetes mellitus.
- •Hypersensitivity to the active substance or to any of the excipients.
- •Known or suspected liver disease, defined by serum transaminase and alkaline phosphatase levels 3 times the normal level.
- •Patients with acute inflammatory or infectious diseases during the 3 months prior to inclusion in the study.
- •Patients with chronic inflammatory, immune or infectious diseases.
- •Patients with a history of cancer within the past 5 years.
- •History of alcohol, drug or medication abuse.
- •Patients exposed to any other type of radiation, medical or professional.
- •Clinically relevant haematological disorders.
- •Decompensated metabolic disorders.
- •Abuse of alcohol or drugs in the previous 3 months.
研究组 & 干预措施
Semaglutide in addition to standard therapy
干预措施: semaglutide (Drug)
Semaglutide in addition to standard therapy
干预措施: Standard Treatment (Guideline-Based) (Drug)
Standard therapy alone
干预措施: Standard Treatment (Guideline-Based) (Drug)
结局指标
主要结局
To evaluate the effects of semaglutide in addition to standard therapy on inflammatory biomarkers compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.
时间窗: From enrollment to the end of treatment at 52 weeks
Regarding this endpoint, the change in inflammatory biomarkers involved in atherogenesis at follow-up compared to baseline will be evaluated in both treatment arms. Inflammatory biomarkers will be measured in serum using an appropriately validated immunoassay (ELISA - enzyme-linked immunosorbent assay). Inflammatory biomarkers include C-reactive protein (CRP), interleukins (IL-1β, IL-6, IL-10), colony-stimulating factors (M-CSF), tumor necrosis factors (TNF-α), interferons (IFN-γ), transforming growth factors (TGF-β), and adiponectin, all measured in picograms per milliliter (pg/mL).
To evaluate the effects of semaglutide in addition to standard therapy on biomarkers of endothelial dysfunction compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.
时间窗: From enrollment to the end of treatment at 52 weeks
Regarding this endpoint, the change in biomarkers involved in endothelial dysfunction at follow-up compared to baseline will be evaluated in both treatment arms. Biomarkers of endothelial dysfunction will be measured in serum using an appropriately validated immunoassay (ELISA - enzyme-linked immunosorbent assay), and include soluble endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin, all measured in nanograms per milliliter (ng/mL).
次要结局
- To correlate FAI at CTA to biomarkers evaluated at 52 weeks in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.(From enrollment to the end of treatment at 52 weeks)
- To correlate characteristics of subclinical atherosclerotic coronary plaques at CTA in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10% to biomarkers evaluated at baseline.(At baseline)
- To retrospectively evaluate fat attenuation index (FAI) at CTA in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.(At baseline retrospectively)
- To retrospectively evaluate characteristics of subclinical atherosclerotic coronary plaques at CTA in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.(At baseline retrospectively)
- To correlate FAI in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10% to biomarkers evaluated at baseline.(At baseline)
- To correlate characteristics of subclinical atherosclerotic coronary plaques at CTA to biomarkers evaluated at 52 weeks in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.(From enrollment to the end of treatment at 52 weeks)
- To associate FAI at CTA with the incidence of MACE evaluated at 52 weeks in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.(From enrollment to the end of treatment at 52 weeks)
- To assess the safety of semaglutide in addition to standard therapy compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.(From enrollment to the end of treatment at 52 weeks)
- To assess the tolerability of semaglutide in addition to standard therapy compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.(From enrollment to the end of treatment at 52 weeks)
研究者
Pasquale Perrone Filardi
Professor
Federico II University