Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease

Personalisation of Non-surgical Treatment in Peripheral Arterial Disease Using a Multicomponent Exercise Approach

Peripheral arterial disease (PAD) is characterised as an atherosclerotic disease, most common in the lower limbs (aortoiliac, femoropopliteal, and infrapopliteal arterial segments), which causes a decrease in blood flow to the areas adjacent to and posterior to the affected area. Intermittent claudication (IC) is the most common symptom in this disease that appears with exertion and relieves with rest, causing fatigue, cramps, discomfort, or pain in the lower limbs due to limited blood flow to the affected muscles. Supervised physical exercise has emerged as the first line of intervention in improving the symptoms of intermittent claudication and disease progression, and in the last decade there has been an exponential increase in the use of wearable technologies to monitor dose-response. However, the approach used is still simplistic because it is not personalised. In other words, patients with similar diagnoses and symptoms get the same treatment, without personalising the stimulus according to their exercise responses and level of adaptation. With this in mind, this study aims to monitoring the real-time response of a multicomponent exercise programme (cardiovascular and resistance training) to personalise the dose-response, and use artificial intelligence models to gather and analyse vast amounts of data towards grouping/differentiating based on individual responses. The main hypothesis is that a supervised multicomponent exercise programme will improve the functional capacity of patients with PAD in a cluster personalised approach.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease; Intermittent Claudication
• Intervention / Treatment: Behavioral: Usual care; Behavioral: Exercise

Detailed Description

Framework: Continuous monitoring of training allows for a better understanding and adjustment of the proposed objectives, based on the physiological responses provided. With the use of wearables increasing significantly and emerging as the main trend since 2016, near-infrared spectroscopy (NIRS) has been gaining emphasis as method for assessing muscle oxygen saturation (SmO2) and is an important tool in exercise monitoring. In the field of PAD, the use of NIRS is also fundamental as it allows the oxygen available in the muscle to be visualised in real time. NIRS technology makes it possible to observe the response to exercise in detail, in terms of deoxygenation and reoxygenation, which are essential analysis processes since PAD is characterised by oxygen insufficiency and the responses are highly individualised. In conjunction, the use of high-precision accelerometry (1600 Hz) helps to identify all the movements made by analysing the responses in the different axes. Based on the considerable gap in the literature regarding the effect of continuous monitoring and personalisation of the dose-response in this population, this study aims to assess the effect of a multicomponent cardiovascular and resistance training programme, personalised, and continuously monitored through heart rate (HR) and SmO2.

The experimental design comprises the following phases: i) programme design; ii) sample recruitment; iii) initial evaluation of the experimental group (Supervised exercise training) and the control group (Usual care) (M0 - 0 week); iv) personalisation of the exercise load; v) programme implementation; and vi) final evaluation of both groups (M1 - 12 weeks after).

Sample: Patients with PAD will be recruited at the Local Health Unit of Trás-os-Montes and Alto Douro, by the Angiology and Vascular Surgery Service. Participation in the study will be voluntary and written informed consent will be obtained from each patient. After the baseline assessments patient will be randomised to 1 of 2 groups, using a random number program with blocking to assure that the group sizes do not differ by >2.

Intervention: There will be two study arms: i) intervention arm - 12 weeks of supervised exercise (cardiovascular and resistance training) three times a week; and ii) comparator arm - a usual care group that will be instructed according to standard lifestyle modification but without specific recommendations about the exercise programme.

Power and sample size calculations: Power analysis performed in G*Power software (using ANOVA repeated measures within-between factors), version 3.1.9.7 (Institut für Experimentelle Psychologie, Düsseldorf, Germany) for an effect size of 0.25, an α of 0.05, and a power of 0.80 (1-ß) showed that 34 patients would be needed to achieve statistical significance. Considering the potential loss to follow-up, an attrition rate of 10% will be added to the calculated n, totalling 38 patients to be recruited.

Statistical analysis: Statistical analyses will be carried out using JASP software, version 0.18.1 (JASP Team, 2023) and the figures produced in GraphPad Prism software, version 8.0.1 (GraphPad Software, San Diego, California).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catarina Abrantes, Ph.D.; Phone Number: 259350000; Email: abrantes@utad.pt
• Study Contact Backup: Name: Daniel Santarém, M.Sc.; Phone Number: 259350000; Email: danielrs@utad.pt

Study Locations

• Portugal
  • Vila Real, Portugal, 5000-508
    • Recruiting
    • Hospital Centre Hospitalar de Trás-os-Montes e Alto Douro
    • Contact: Irene Pinto
    • Sub-Investigator: Jacinta Campos, M.Sc.
    • Sub-Investigator: Irene Pinto, M.Sc.
  • Vila Real, Portugal, 5000-801
    • Recruiting
    • Research Centre in Sports Sciences, Health Sciences and Human Development
    • Contact: Catarina Abrantes, Ph.D.; Phone Number: 934286001; Email: abrantes@utad.pt
    • Principal Investigator: Catarina Abrantes, Ph.D.
  • Vila Real, Portugal, 5000-801
    • Recruiting
    • University of Trás-os-Montes and Alto Douro
    • Principal Investigator: Catarina Abrantes, Ph.D.
    • Contact: Catarina Isabel Neto Gavião Abrantes, Ph.D.; Phone Number: 934286001; Email: abrantes@utad.pt
    • Sub-Investigator: Daniel Santarém, M.Sc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with clinically stable PAD;
• An ankle-brachial index (ABI) between 0.41-0.90 at rest in one or both lower limbs;
• Mild to moderate claudication, corresponding to Fontaine Stage IIa and IIb;
• A history of ambulatory leg pain;
• Ambulatory leg pain confirmed by treadmill test;
• Able to provide written consent.

Exclusion Criteria:

• Noncompressible, calcified, tibial arteries (resting ABI ≥ 1.4);
• Use of medication that could influence claudication (e.g. Cilostazol or Pentoxifylline) 3 months prior to investigation;
• Previous intervention (e.g. balloon angioplasty, stenting, bypass, exercise programme);
• Inability to walk on a treadmill at a speed of 3.2 km/h (2 mph);
• Participation in the past 3 months in a clinical trial or exercise program;
• Asymptomatic PAD determined from the medical history;
• Exercise limited by factors other diseases or conditions than intermittent claudication;
• Angina pectoris, congestive heart failure, chronic obstructive pulmonary disease, severe arthritis, or limb amputation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supervised multicomponent exercise; Experimental arm will perform the supervised exercise programme three times a week, with each session taking approximately 60-80 minutes for a period of 12 weeks.	Behavioral: Exercise; Patients randomised to the intervention arm will undergo non-consecutive training sessions three times a week for a period of 12 weeks. The training session is divided into an aerobic and a resistance training component, with a 5-min warm-up (stretching exercises) and a 5-min cool-down (stretching and relaxing exercises). The cardiovascular component will comprise a progressive exercise duration from 30 to 40 minutes, an exercise intensity promoting moderate to severe claudication pain between 8-12 minutes, with rest time until the pain disappears, and a personalised load progression manipulated based on the claudication pain level, reaching a total of 60 minutes of walking per session. The resistance training component will comprise dynamic muscle contraction exercises (Leg extension, unilateral hip extension, and standing calf raise), with a load progression from 50% of 1-estimated one repetition maximum (e-RM) to 80% of 1-eRM.
Active Comparator: Usual care; Active comparator arm will be advised to lifestyle modification and to perform regular walking for a period of 12 weeks.	Behavioral: Usual care; Patients randomised to the active comparator arm will be advised about the importance of lifestyle modification (including general advice to increase walking but without specific recommendations about the exercise program) for a period of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain-free walking distance	Distance until onset of claudication (in meters) will be measured in patients undergoing the graded treadmill exercise test (Gardner-Skinner protocol).	Baseline and 12 weeks
Maximum walking distance	Walking distance until maximum claudication (in meters) will be measured in patients undergoing the graded treadmill exercise test (Gardner-Skinner protocol).	Baseline and 12 weeks
Percentage of muscle deoxygenation	The percentage of muscle deoxygenation (in %) will be measured in patients undergoing the graded treadmill exercise test (Gardner-Skinner protocol).	Baseline and 12 weeks
Muscle reoxygenation time	The muscle reoxygenation time (in seconds) will be measured in patients undergoing the graded treadmill exercise test (Gardner-Skinner protocol).	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain-free walking distance	Distance until onset of claudication (in meters) will be measured in patients undergoing the 6-minute walk test.	Baseline and 12 weeks
Maximum walking distance	Walking distance until maximum claudication (in meters) will be measured in patients undergoing the 6-minute walk test.	Baseline and 12 weeks
Percentage of muscle deoxygenation	The percentage of muscle deoxygenation (in %) will be measured in patients undergoing the 6-minute walk test.	Baseline and 12 weeks
Muscle reoxygenation time	The muscle reoxygenation time (in seconds) will be measured in patients undergoing the 6-minute walk test.	Baseline and 12 weeks
Lower limb muscle strength assessment	The peak force (in kg) will be measured in patients using the hand-held dynamometry test.	Baseline and 12 weeks
Lower limb muscle power assessment	The rate of force development (in kg/s) will be measured in patients using the hand-held dynamometry test.	Baseline and 12 weeks
Resting systolic blood pressure	The resting systolic blood pressure (in mmHg) will be measured in patients after a 10-minute rest in a lying position.	Baseline and 12 weeks
Resting diastolic blood pressure	The resting diastolic blood pressure (in mmHg) will be measured in patients after a 10-minute rest in a lying position.	Baseline and 12 weeks
Life quality	The quality of life will be measured in patients using the 36-Item Short Form Survey that contains the domains of mental component and physical component.	Baseline and 12 weeks
Daily walking ability	The daily walking will be measured in patients using the Walking Impairment Questionnaire that contains the domains of walking distance, walking speed and ability to climb stairs.	Baseline and 12 weeks
Fasting blood glucose	The fasting blood glucose (in mg/dL) will be measured in patients using the fasting blood glucose test.	Baseline and 12 weeks
Sedentary behaviour	The sedentary behaviour (in min/day) will be measured in patients over seven consecutive days.	Baseline and 12 weeks
Moderate-to-vigorous physical activity	Moderate-to-vigorous physical activity (in min/day) will be measured in patients over seven consecutive days.	Baseline and 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ankle-brachial index	The ankle-brachial index (in a.u.) will be measured in patients after a 10-minutes rest in a lying position.	Baseline and 12 weeks
Body composition	The body composition (the unit will depend on the derived-parameters evaluated) will be measured in patients in the orthostatic position according to guidelines.	Baseline and 12 weeks
Cross-sectional area of the gastrocnemius medialis muscle	The cross-sectional area of the gastrocnemius medialis muscle of both lower limbs will be determined through an echographic evaluation.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: University of Trás-os-Montes and Alto Douro
• Collaborators: Hospital Centre Hospitalar de Trás-os-Montes e Alto Douro; Research Center in Sports Sciences, Health Sciences and Human Development
• Investigators: Principal Investigator: Catarina Abrantes, Ph.D., University of Trás-os-Montes and Alto Douro, Vila Real, Portugal

Publications and helpful links

General Publications

• Aboyans V, Ricco JB, Bartelink MEL, Bjorck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Rother J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018 Mar 1;39(9):763-816. doi: 10.1093/eurheartj/ehx095. No abstract available.
• Perrey S, Ferrari M. Muscle Oximetry in Sports Science: A Systematic Review. Sports Med. 2018 Mar;48(3):597-616. doi: 10.1007/s40279-017-0820-1.
• Cornelis N, Chatzinikolaou P, Buys R, Fourneau I, Claes J, Cornelissen V. The Use of Near Infrared Spectroscopy to Evaluate the Effect of Exercise on Peripheral Muscle Oxygenation in Patients with Lower Extremity Artery Disease: A Systematic Review. Eur J Vasc Endovasc Surg. 2021 May;61(5):837-847. doi: 10.1016/j.ejvs.2021.02.008. Epub 2021 Mar 30.
• Baltrunas T, Mosenko V, Mackevicius A, Dambrauskas V, Asakiene I, Rucinskas K, Narmontas P. The use of near-infrared spectroscopy in the diagnosis of peripheral artery disease: A systematic review. Vascular. 2022 Aug;30(4):715-727. doi: 10.1177/17085381211025174. Epub 2021 Jun 10.
• Nordanstig J, Behrendt CA, Bradbury AW, de Borst GJ, Fowkes F, Golledge J, Gottsater A, Hinchliffe RJ, Nikol S, Norgren L. Peripheral arterial disease (PAD) - A challenging manifestation of atherosclerosis. Prev Med. 2023 Jun;171:107489. doi: 10.1016/j.ypmed.2023.107489. Epub 2023 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 13, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Peripheral arterial disease; Supervised multicomponent exercise programme
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Intermittent Claudication
• Other Study ID Numbers: PASSUS 2.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No