Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease

Peripheral Arterial Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06410521
• Other study ID #: PASSUS 2.0
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2024
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: University of Trás-os-Montes and Alto Douro
• Contact: Catarina Abrantes, Ph.D.
• Phone: 259350000
• Email: abrantes[@]utad.pt
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Experimental design: The experimental design comprises the following phases: i) programme design; ii) sample recruitment; iii) initial evaluation of the experimental group and the usual care group (M0); iv) personalisation of the load; v) programme implementation; vi) mid-term evaluation (M1 - 3 months after) of the experimental group and the usual care group; vii) continued implementation of the programme; viii) final evaluation of the experimental group and the usual care group (M2 - 6 months 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 the Number Cruncher Statistical System 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 - 24 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 0.95 (1-ß ) showed that 44 patients would be needed to achieve statistical significance.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Intermittent Claudication
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Behavioral:
• Exercise
Patients randomised to the intervention arm will undergo non-consecutive training sessions three times a week for a period of 24 weeks. The training session is divided into a cardiovascular and a resistance training component. The cardiovascular component will comprise a progressive exercise duration from 30 to 40 minutes, an exercise intensity promoting moderate to severe claudication pain between 5-10 minutes, with rest time until the pain disappears, and a personalised load progression manipulated based on the claudication pain level, reaching a total of 50 minutes of walking per session. The resistance training component will comprise dynamic muscle contraction exercises (shoulders width squat, unilateral chair leg extension, and bilateral plantar flexion), with a load progression gradually increasing from one set of 10 repetitions to three sets of 15 repetitions.
• 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 24 weeks.

Locations

Country	Name	City	State
Portugal	Hospital Centre Hospitalar de Trás-os-Montes e Alto Douro	Vila Real
Portugal	Research Centre in Sports Sciences, Health Sciences and Human Development	Vila Real
Portugal	University of Trás-os-Montes and Alto Douro	Vila Real

Sponsors (3)

Lead Sponsor	Collaborator
University of Trás-os-Montes and Alto Douro	Hospital Centre Hospitalar de Trás-os-Montes e Alto Douro, Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD)

Country where clinical trial is conducted

Portugal, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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, 3 and 6 months
Other	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, 3 and 6 months
Primary	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, 3 and 6 months
Primary	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, 3 and 6 months
Primary	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, 3 and 6 months
Primary	Muscle reoxygenation time	The muscle reoxygenation time (in seconds) will be measured in patients undergoing the graded treadmill exercise test (Gardner-Skinner protocol).	Baseline, 3 and 6 months
Secondary	Pain-free walking distance	Distance until onset of claudication (in meters) will be measured in patients undergoing the 6-minute walk test.	Baseline, 3 and 6 months
Secondary	Maximum walking distance	Walking distance until maximum claudication (in meters) will be measured in patients undergoing the 6-minute walk test.	Baseline, 3 and 6 months
Secondary	Percentage of muscle deoxygenation	The percentage of muscle deoxygenation (in %) will be measured in patients undergoing the 6-minute walk test.	Baseline, 3 and 6 months
Secondary	Muscle reoxygenation time	The muscle reoxygenation time (in seconds) will be measured in patients undergoing the 6-minute walk test.	Baseline, 3 and 6 months
Secondary	Lower limb muscle strength assessment	The peak force (in kg) will be measured in patients using the hand-held dynamometry test.	Baseline, 3 and 6 months
Secondary	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, 3 and 6 months
Secondary	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, 3 and 6 months
Secondary	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, 3 and 6 months
Secondary	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, 3 and 6 months
Secondary	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, 3 and 6 months
Secondary	Fasting blood glucose	The fasting blood glucose (in mg/dL) will be measured in patients using the fasting blood glucose test.	Baseline, 3 and 6 months
Secondary	Sedentary behaviour	The sedentary behaviour (in min/day) will be measured in patients over seven consecutive days.	Baseline and 6 months
Secondary	Moderate-to-vigorous physical activity	Moderate-to-vigorous physical activity (in min/day) will be measured in patients over seven consecutive days.	Baseline and 6 months