CT Body Composition as Predictor of Exercise Therapy Outcome in Peripheral Arterial Disease (COMPOSE-PAD)

February 20, 2026 updated by: Matej Pekar, MD, PhD, Nemocnice AGEL Trinec-Podlesi a.s.

CT Body Composition Predicts Supervised Exercise Response in Peripheral Arterial Disease: A Protocol

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Detailed Description

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.

H2: Higher VAT area (cm²) independently predicts SET treatment failure. H3: The sarcopenic obesity phenotype (co-occurrence of low muscle density and elevated VAT) is associated with the lowest SET treatment success rates across four body composition phenotype groups.

STUDY DESIGN Prospective, single-centre observational cohort study. February 2023 - December 2026. Complex Cardiovascular Centre, Hospital AGEL Trinec-Podlesi, Trinec, Czech Republic. Ethics approval: EK 314/22. Reported per STROBE and TRIPOD guidelines; SPIRIT 2013 checklist provided as supplementary file.

INTERVENTION (standard clinical care, not study-allocated) 36 supervised exercise sessions (3×/week × 12 weeks), per 2019 AHA Scientific Statement on optimal exercise programmes for PAD. Each session: 60 minutes (45 min structured exercise + 15 min patient education). Treadmill exercise at 3.2 km/h, walking to claudication level 3 on a four-point scale, rest to level 1, five to six cycles per session. Progression: speed +0.3 km/h every two weeks (weeks 1-4, maximum 4.0 km/h); grade +1% every two weeks (weeks 5-8, maximum 3%). Resistance training from week 5 (2 sets × 10 repetitions progressing to 5 sets at ~70% one-repetition maximum, major lower extremity muscle groups). Adequate adherence defined as ≥30 of 36 sessions.

CT BODY COMPOSITION L3 axial CT slice; AutoMATiCA U-Net neural network segmentation; ~350 ms/scan.

  • Skeletal muscle: -29 to +150 HU within muscle fascia mask
  • VAT: -150 to -50 HU within peritoneal cavity mask
  • SAT: -190 to -30 HU exterior to body wall
  • IMAT: -190 to -30 HU within muscle fascia, exterior to individual muscle boundaries Baseline (T0) from existing diagnostic CTA; repeat CT at 3 months (T1) for exploratory analysis.

PRIMARY OUTCOME Composite at 3 months: (a) functional improvement ≥50 m absolute or ≥50% relative MWD gain on standardised treadmill (3.2 km/h); AND (b) revascularisation-free status (no endovascular or surgical lower extremity revascularisation). Treatment success = both criteria met. Revascularisation events adjudicated by vascular surgeon blinded to body composition data.

STATISTICAL ANALYSIS Multivariable logistic regression; predictors z-score standardised; bootstrap internal validation (1,000 samples); optimism-corrected AUC, calibration slope, calibration-in-the-large. Bonferroni-corrected p < 0.017 per co-primary hypothesis. Fine-Gray subdistribution hazard model for competing risks (death). Multiple imputation by chained equations (MICE; 20 imputed datasets). Pre-specified sensitivity analyses (n=13) including composite threshold alternatives, component-separate analyses, three-predictor model, alternative HU and VAT thresholds, adherent subgroup analysis.

SAMPLE SIZE Target: 40 treatment failures = 10 events per variable for four-predictor model; yields AUC confidence interval ±0.10. Assuming 40% failure rate and 22% attrition: 128 enrolled → 100 evaluable → 40 failures. Supplementary power: 80% to detect OR ≥2.0 per 10 HU decrease in muscle density (α = 0.05, two-tailed).

DERIVATION STATUS This is an explicit derivation cohort. AUC precision of ±0.10 at 40 events is pre-stated; conclusions will be confined to predictor association direction and magnitude. External multicentre validation is the pre-specified mandatory next step.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
128

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Consecutive adult patients with Fontaine IIa-IIb intermittent claudication attending the vascular surgery outpatient clinic at the Complex Cardiovascular Centre, Hospital AGEL Trinec-Podlesi, Trinec, Czech Republic, who are scheduled for the institutional supervised exercise therapy programme and have an existing CT angiography with an analysable L3 axial slice.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite supervised exercise therapy treatment success at 3 months
Time Frame: 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.
3 months from enrolment (end of supervised exercise therapy programme)

Collaborators and Investigators

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Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nemocnice AGEL Trinec-Podlesi a.s.

Study record dates

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Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 20, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 20, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 25, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 25, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EK-314-22-PAD-BC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared publicly at this stage. Anonymised aggregate summary data supporting the study findings will be made available upon reasonable request to the corresponding author following publication of the primary results, subject to applicable data protection regulations (GDPR).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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