High-intensity Intervals Versus Low-to-moderate-intensity Exercise Training in Patients With PAD (HIIT_PAD)

Short-duration Aerobic High-intensity Intervals Versus Low-to-moderate-intensity Exercise Training in Symptomatic Patients With Peripheral Artery Disease: A Randomized Controlled Trial

Supervised exercise training (SET) is considered among first-line therapies for patients with symptomatic lower extremity peripheral artery disease (PAD), combined with general cardiovascular risk management, lifestyle adaptation and pharmacological treatment.

Although without clear consistency, the guidelines give recommendations in terms of claudication pain severity, SET volume, duration, and frequency. However, no or little guidance is offered as far as training intensity is concerned. Most of the previous studies on SET, in the context of PAD, did not distinguish between symptom intensity and common training intensity measures such as % of maximal heart rate (%HRmax), % of HR reserve (%HRR), % of peak oxygen uptake (%VO2peak), % of VO2 reserve (%VO2R), or the rate of perceived exertion (RPE).

In a recent meta-analysis, we demonstrated that both training modality and exercise intensity (based on %peak heart rate, %peak oxygen uptake, or the rate of perceived exertion) should be considered when looking for the best results in patients with symptomatic PAD. These results call for study of the individual roles of each exercise intensity and modality on walking performance and cardiorespiratory fitness in patients with symptomatic PAD.

High-intensity interval training (HIIT) is composed of brief bursts of vigorous intensity interspersed with periods of rest or low-intensity exercise. HIIT may be better than moderate-intensity training (MIT) in improving cardiorespiratory fitness and functional capacity in patients with cardiovascular and metabolic diseases, but in patients with symptomatic PAD, the effects of such modalities on walking ability and cardiorespiratory fitness remain to be clearly determined.

The primary objective of this study is to compare the effects of 12-week-long exercise training (short-duration high-intensity intervals vs. low-to-moderate intensity) on treadmill performance in patients with symptomatic PAD.

It is hypothesized that treadmill performance would be improved to a greater extent after high-intensity exercise training

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Other: High-intensity interval training group (HIIT); Other: Low-to-moderate intensity training group (LowMod group)

Detailed Description

Lower extremity peripheral artery disease (PAD) affects more than 200 million people worldwide. PAD is characterized by atherosclerotic lumen narrowing or occlusion of the lower limb arteries, leading to an imbalance between oxygen supply and demand downstream, especially in activated muscle during exertion. The hallmark symptom of PAD is typical intermittent claudication, defined as reproducible exertion-induced cramping or pain in the lower extremities, which is rapidly relieved with rest.

Patients with symptomatic PAD avoid exertion and tend to have muscle weakness, an altered gait and lower limb biomechanics. This results in impaired walking performance, accelerated functional decline, and reduced quality of life.

Supervised exercise training (SET) is considered among first-line therapies for patients with symptomatic PAD, combined with general cardiovascular risk management, lifestyle adaptation and pharmacological treatment. The clinical benefits of SET for patients with PAD are well established, with improved walking capacity and an improved quality of life as the primary outcomes.

Although without clear consistency, the guidelines give recommendations in terms of claudication pain severity, SET volume, duration, and frequency. However, no or little guidance is offered as far as training intensity is concerned. Most of the previous studies on SET, in the context of PAD, did not distinguish between symptom intensity and common training intensity measures such as % of maximal heart rate (%HRmax), % of HR reserve (%HRR), % of peak oxygen uptake (%VO2peak), % of VO2 reserve (%VO2R), or the rate of perceived exertion (RPE).

A meta-analysis by Parmenter et al. showed that vigorous (%HRpeak: 77-96, %VO2peak: 64-90, RPE: 14-17) exercise training improved cardiorespiratory fitness (VO2peak) more than light- to-moderate exercise therapy intensity in patients with PAD, but the changes in walking performance in these patients remain to be determined. In a recent meta-analysis, we demonstrated that both training modality and exercise intensity (based on %peak heart rate, %peak oxygen uptake, or the rate of perceived exertion) should be considered when looking for the best results in patients with symptomatic PAD. More precisely, we showed that, when training modalities were considered, walking at vigorous intensity showed the greatest improvement in maximal walking distance (MWD), while walking at light-to-moderate intensity showed the greatest improvement in pain-free walking distance. We also showed that vigorous was superior to light-to-moderate exercise intensity in improving cardiorespiratory fitness; and that, when training modalities were considered, cycling and other non-walking forms of training performed at vigorous intensity elicited the greatest improvements in cardiorespiratory fitness.

The results of our meta-analysis call for study of the individual roles of each exercise intensity and modality on walking performance and cardiorespiratory fitness in patients with symptomatic PAD.

High-intensity interval training (HIIT) is composed of brief bursts of vigorous intensity interspersed with periods of rest or low-intensity exercise. HIIT may be better than moderate-intensity training (MIT) in improving cardiorespiratory fitness and functional capacity in patients with cardiovascular and metabolic diseases, but in patients with symptomatic PAD, the effects of such modalities on walking ability and cardiorespiratory fitness remain to be clearly determined.

The primary objective of this study is to compare the effects of 12-week-long exercise training (short-duration high-intensity intervals vs. low-to-moderate intensity) on treadmill performance in patients with symptomatic PAD.

It is hypothesized that treadmill performance would be improved to a greater extent after high-intensity exercise training

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Recruiting
      • CHUV
      • Contact: Lucia Mazzolai, Prof; Phone Number: +41213144700; Email: lucia.mazzolai@chuv.ch
      • Contact: Stefano Lanzi, PhD; Phone Number: +41795564911; Email: stefano.lanzi@chuv.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients with symptomatic PAD (Fontaine stage IIa/b);
• ABI ≤ 0.9 or drop by 20% following exercise treadmill test 1;
• TBI ≤ 0.6 if incompressible arteries (diabetes and renal insufficiency);
• Signed written informed consent form.

Exclusion Criteria:

• Age < 18;
• Unable to walk at 3.2 km/h on a treadmill (slope 0%) at least 300 m;
• Previous participate in SET programs ≤ 1 year;
• Prior leg/foot amputation;
• Contraindication to exercise
• Neurological and neuromuscular disorders and other comorbidities (orthopedic, rheumatologic) leading to gait abnormalities.
• Known Pregnancy
• Incapacity of discernment

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: High-intensity interval training group (HIIT); Exercise training sessions will consist in an alternation of brief periods (≤ 60 s) of work performed at high intensity and brief period of passive rest. Patient will be asked to complete 1 set of 10-15x60-s (or 2 sets of 5-7x60-s) walking intervals. This protocol will elicits moderate-to-severe claudication pain during exertion. The training intensity in the HIIT group will be set at ≥85% HRpeak recorded during the maximal cardiopulmonary exercise test.	Other: High-intensity interval training group (HIIT); Exercise training sessions will consist in an alternation of brief periods (≤ 60 s) of work performed at high intensity and brief period of passive rest. Patient will be asked to complete 1 set of 10-15x60-s (or 2 sets of 5-7x60-s) walking intervals. The training intensity in the HIIT group will be set at ≥85% HRpeak recorded during the maximal cardiopulmonary exercise test. The training intervention will consist of 36 walking sessions spread over 12 weeks. Each training session will lasted 30-60 min. The training intervention will be performed on a treadmill (Cosmed T150, Itlay), which is equipped with harness and chest belt to secure the patients and prevents falling. Each session started with a 5-min walking warm-up and ended with a 5min cool-down. During all the exercise training sessions, HR of the subjects will be continuously monitored (Polar M430, Finland).
Experimental: Low-to-moderate intensity training group (LowMod group); Exercise training sessions will consist in an alternation of periods of work performed at moderate exercise intensity and period of passive rest. The training approach of the LowMod group will be similar to the training prescription usually adopted in patients with claudication. The exercise training intensity will be set at ≤76% HRpeak recorded during the maximal cardiopulmonary exercise test.	Other: Low-to-moderate intensity training group (LowMod group); Exercise training sessions will consist in an alternation of periods of work performed at moderate exercise intensity and period of passive rest. The training approach of the LowMod group will be similar to the training prescription usually adopted in patients with claudication. The exercise training intensity will be set at ≤76% HRpeak recorded during the maximal cardiopulmonary exercise test. The training intervention will consist of 36 walking sessions spread over 12 weeks. Each training session will lasted 30-60 min. The training intervention will be performed on a treadmill (Cosmed T150, Itlay), which is equipped with harness and chest belt to secure the patients and prevents falling. Each session started with a 5-min walking warm-up and ended with a 5min cool-down. During all the exercise training sessions, HR of the subjects will be continuously monitored (Polar M430, Finland).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal walking distance	Patients will perform an incremental treadmill test to determine the maximal walking distance (MWD). Initial walking speed will be set at 3.2 km/h, and at 0% grade. The grade will be increased by 2% each 2 min.	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiorespiratory fitness (VO2peak)	Patients will perform a maximal cardiopulmonary exercise test	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Muscle oxygenation during treadmill test	Muscle oxygenation will be assessed during treadmill test by near-infrared spectroscopy (NIRS)	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Self-perceived quality of life and walking (dis)abilities	Self-perceived quality of life (Medical Outcomes Study Short-Form 36 (SF-36) and walking (dis)abilities (Walking Impairement Questionnaire, WIQ) will be assessed. Each questionnaire has scores on a 0-100 scale (0 (worse score) to 100 (best score)).	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Total amount of physical activity	The total amount of physical activity will be assessed by accelerometer.	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Pain-free walking distance	Patients will perform an incremental treadmill test to determine the pain-free walking distance (PFWD). Initial walking speed will be set at 3.2 km/h, and at 0% grade. The grade will be increased by 2% each 2 min.	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Functional performance - 6-minute walk test	Patients will perform the 6-minute walk test	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Functional performance - ascending and descending stair performance test	Patients will perform the ascending and descending stair performance test	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Functional performance - short physical performance battery test	Patients will perform the short physical performance battery test	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Functional performance - preferred walking speed and gait analysis assessment	Patients will perform the preferred walking speed and gait analysis assessment	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Functional performance - unipedal stance test	Patients will perform the unipedal stance test	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Functional performance - 30- and 60-s repeated sit-to-stand chair test	Patients will perform the 30- and 60-s repeated sit-to-stand chair test.	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.
Hemodynamic parameters	Ankle - toe brachial index (ABI, TBI)	This will be assessed before and after the 3-month training program. The post-program assessment will be performed between 5 to 14 days following the last training session.

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): July 1, 2023
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: November 7, 2022
• First Posted (Actual): November 10, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Rehabilitation; Exercise; Physical activity
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: Exercise_intensity_PAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No