CT Body Composition Predicts Supervised Exercise Response in Peripheral Arterial Disease: A Protocol
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 128
- 主要终点
- Composite supervised exercise therapy treatment success at 3 months
研究概览
简要总结
Supervised exercise therapy (SET) is the recommended first treatment for patients with leg artery disease (peripheral arterial disease, PAD) causing pain when walking. However, approximately 40% of patients do not benefit meaningfully and go on to require a procedure to open the blocked arteries within three months. This study investigates whether body composition measurements - specifically the quality of muscle and the amount of belly fat - taken from a CT scan already performed as part of routine care, can identify before treatment begins which patients are unlikely to respond to exercise therapy. If confirmed, this approach would allow doctors to use information from a scan patients are already having, with no additional tests, to better match patients to the right treatment from the start.
详细描述
BACKGROUND Peripheral arterial disease (PAD) affects approximately 236 million adults worldwide. Intermittent claudication - exertional lower limb ischaemic pain that resolves with rest - is its most prevalent symptomatic form. Three 2024 international guidelines (ACC/AHA, ESC, ESVS) unanimously recommend supervised exercise therapy (SET) as first-line treatment before revascularisation. Two Cochrane systematic reviews confirm that SET significantly improves maximum walking distance and quality of life compared with home-based exercise and walking advice alone. Despite population-level efficacy, individual response is highly heterogeneous: approximately 40% of patients fail to achieve meaningful functional improvement or require revascularisation within three months of initiating SET. Conventional predictors - ankle-brachial index and baseline claudication distance - do not reliably predict the magnitude of SET response. No validated pre-therapy metabolic tool exists to identify patients who lack the biological substrate for aerobic adaptation.
RATIONALE Chronic lower-limb ischaemia causes progressive skeletal muscle remodelling - including intramuscular lipid infiltration, fibre-type shift toward type IIx fibres, and mitochondrial dysfunction - that directly constrains the aerobic adaptation capacity upon which SET depends. CT-derived skeletal muscle attenuation (Hounsfield units, HU) quantifies intramuscular lipid with excellent reproducibility (coefficient of variation <1%). Single-slice CT analysis at the L3 vertebral level provides whole-body body composition estimates correlated with DXA (r = 0.86-0.94) and is a validated systemic metabolic phenotyping tool - it reflects whole-body metabolic reserve, not ischaemia-specific lower limb myopathology. Visceral adipose tissue (VAT) is an independent pro-inflammatory and endocrine compartment that impairs aerobic exercise adaptation through systemic mechanisms. CT angiography (CTA) is routinely performed in symptomatic PAD patients being evaluated for revascularisation; L3 body composition extraction from existing CTA incurs zero additional patient burden. The research group has previously demonstrated that L3 CT body composition parameters predict overall survival after transcatheter aortic valve implantation using the same methodology (Pekar et al., Sci Rep 2024; Kantor et al., Cor Vasa 2025).
STUDY AIMS Primary: To determine whether L3 CT-derived skeletal muscle density and VAT area, extracted opportunistically from existing diagnostic CTA, independently predict composite SET treatment success at three months in patients with Fontaine IIa-IIb intermittent claudication.
Three co-primary hypotheses:
H1: Lower skeletal muscle density (HU) independently predicts SET treatment failure.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •Confirmed peripheral arterial disease (PAD) defined by at least one of: resting ankle-brachial index (ABI) ≤0.90, duplex ultrasonography demonstrating ≥50% stenosis in a relevant lower extremity vessel, or CT angiography (CTA) or magnetic resonance angiography (MRA) demonstrating flow-limiting lower extremity arterial disease
- •Fontaine stage IIa or IIb intermittent claudication
- •Scheduled for the institutional 36-session supervised exercise therapy (SET) programme
- •Existing CTA with an axial slice at the L3 vertebral level suitable for automated body composition analysis
- •Capacity to provide written informed consent
排除标准
- •Fontaine stage III or IV peripheral arterial disease (rest pain or tissue loss; critical limb-threatening ischaemia)
- •Ipsilateral lower extremity revascularisation within 6 months prior to enrolment
- •Absolute contraindication to structured exercise (e.g., unstable coronary artery disease, severe pulmonary hypertension, uncontrolled arrhythmia, or other condition precluding participation in a supervised treadmill and resistance exercise programme)
- •Cognitive impairment (Mini-Mental State Examination [MMSE] score <24)
- •Active malignancy or systemic condition expected to substantially alter body composition independently of the exercise intervention during the study period
- •Estimated life expectancy less than 12 months
结局指标
主要结局
Composite supervised exercise therapy treatment success at 3 months
时间窗: 3 months from enrolment (end of supervised exercise therapy programme)
Binary composite endpoint requiring both: (1) Functional improvement - absolute increase in maximum walking distance (MWD) ≥50 m OR relative increase ≥50% from baseline on standardised graded treadmill testing (3.2 km/h); AND (2) Revascularisation-free status - no endovascular or surgical lower extremity revascularisation during the 3-month programme period. Treatment success = both criteria met; treatment failure = failing either criterion. MWD assessed by trained physiotherapist blinded to CT body composition data. Revascularisation events independently adjudicated by a vascular surgeon blinded to body composition predictor values.
次要结局
未报告次要终点
研究者
Matej Pekar, MD, PhD
Principal Investigator
Nemocnice AGEL Trinec-Podlesi a.s.