Acute Local Metabolomic Alterations in Blood and Muscle Tissue in Intermittent Claudication
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in local metabolomic profile after treadmill exercise as reflected by arteriovenous gradients of low-molecular metabolites.
研究概览
简要总结
The most common clinical presentation of lower extremity arterial disease is intermittent claudication. Current understanding of the pathophysiology of intermittent claudication, as well as its treatment options are limited. The progression of the disease may lead to lower limb amputation, which is devastating for patients' quality of life and is a huge socio-economic burden to society.
Current study allows to determine the acute local metabolomic alterations in the ischaemic limb of the patient with intermittent claudication, and investigate the associations between the metabolomic alterations and the patient's maximal walking distance. This provides potentially valuable insight into the pathophysiology of this disease, and helps lay the groundwork for identifying potential novel targets for instituting more effective therapies for this high-risk population.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •LEAD group: Patients with diagnosis of lower extremity arterial disease (Fontaine IIa).
- •Control group: Healthy volunteers with no leg symptoms and an ankle-brachial index (ABI) of 1.0-1.4.
排除标准
- •Fontaine stages I or IIb-IV
- •Exacerbation of limb ischaemia within the preceding 2 weeks;
- •strong rest pain of any cause;
- •age <18 or >80 years;
- •fasting < 6 hours;
- •time since last use of tobacco products < 6 hours;
- •body mass index ≥ 35 kg/m2
- •poor sonographic visibility of femoral artery;
- •cardiac arrhythmia at the time of presentation;
- •presence of cardiac pacemaker;
- •myocardial infarction within the preceding 3 months;
- •stroke within the preceding 6 months;
- •ongoing anticoagulant therapy;
- •ongoing dual antiplatelet therapy;
- •any revascularization within the preceding 3 month;
- •marked heart failure (NYHA III-IV);
- •blood pressure ≥ 180/110 mmHg;
- •blood pressure <100/70 mmHg;
- •clinically significant heart valve disease;
- •acute infectious disease;
- •active malignancy or chemotherapy or disease-free < 5 years;
- •type I diabetes or insulin therapy;
- •other clinically significant and untreated endocrine disorders;
- •moderate to severe bronchial asthma (GINA 2016);
- •severe chronic obstructive pulmonary disease (mMRC grade 3-4);
- •acute (KDIGO 2012) or chronic renal disease (eGFR-EPI <30mL/min/1.73 m2);
- •acute or chronic liver disease;
- •anemia (<110 g/L);
- •neuroinflammatory or neurodegenerative disease;
- •active rheumatism;
- •other diseases and factors that markedly hinder the subject's ability to walk during the treadmill exercise.
- •For control group exclusively: history of lower extremity arterial disease / ABI <1.0 or >1.4.
结局指标
主要结局
Change in local metabolomic profile after treadmill exercise as reflected by arteriovenous gradients of low-molecular metabolites.
时间窗: Blood sampling at two points in time: Baseline (Day 1) & 10-15 minutes after treadmill test (Day 2).
Measured using liquid chromatography combined with mass spectrometry (AbsoluteIDQ MxP Quant 500 Kit, BIOCRATES Life Sciences AG, Austria).
Change in local inflammatory profile after treadmill exercise as reflected by arteriovenous gradients of inflammatory mediators (IL-6, MPO, SOD, NOX isoform 1, NOX isoform 2, NOX isoform 5, nitrotyrosine, 8-iso-PGF2α).
时间窗: Blood sampling at two points in time: Baseline (Day 1) & 10-15 minutes after treadmill test (Day 2).
Measured using enzyme linked immunosorbent assay. Measurement unit: ng/mL.
次要结局
- Change in local metabolomic profile after treadmill exercise as reflected by absolute concentrations of low-molecular metabolites in muscle biopsy.(Biopsy at two points in time: Baseline (Day 1) & 15-20 minutes after treadmill test (Day 2).)
- Correlations between maximal walking distance and exercise-induced changes in local metabolomic and inflammatory profiles.(Data analysis after the enrollment period.)
- Correlations between baseline arterial functionality/hemodynamic parameters and exercise-induced changes in local metabolomic and inflammatory profiles.(Data analysis after the enrollment period.)
研究者
Jaak Kals, MD
Professor
University of Tartu