Peripheral Arterial Disease (PAD) of the lower extremities is common and prevalence of PAD is increasing in our aging population. The presence of PAD is associated with increased cardiovascular morbidity and mortality, reduced physical function and quality of life. Intermittent claudication is the most common symptom of PAD affecting about 30% of the patients. Supervised exercise therapy (SET) is safe and cost-effective therapy when compared with invasive revascularization, and is recommended as the first-line treatment for symptomatic PAD. However, SET is not readily available in the public healthcare system. Barriers to SET implementation include demands for healthcare resources and the inconvenience of travelling to designated centre for SET. Home-based exercise therapy (HBET) has been proposed as an alternative to SET as they are more accessible and more acceptable to patients, but the benefits of HBET compared to SET have not been consistently demonstrated in studies. Wearable activities monitor (WAM) have been proposed as an adjuvant to enhance the performance of HBET. However, there is no direct comparison of WAM enhanced HBET to SET. Furthermore, WAMs were mainly used for monitoring in HBET in the previous studies and patient feedback was conducted either in-person or over telephones by the researchers, which challenges the true meaning of HBET. In this study, we aim to evaluate the non-inferiority of personalized self-guided HBET enhanced with WAM and auto feedback mobile apps, to SET, in a randomized-controlled trial of patients with symptomatic PAD.
Peripheral Arterial Disease (PAD) of the lower extremities is common and prevalence of PAD is increasing in our aging population. The presence of PAD is associated with increased cardiovascular morbidity and mortality, reduced physical function and quality of life. Intermittent claudication is the most common symptom of PAD affecting about 30% of the patients. Supervised exercise therapy (SET) is safe and cost-effective therapy when compared with invasive revascularization, and is recommended as the first-line treatment for symptomatic PAD. However, SET is not readily available in the public healthcare system. Barriers to SET implementation include demands for healthcare resources and the inconvenience of travelling to designated centre for SET. Home-based exercise therapy (HBET) has been proposed as an alternative to SET as they are more accessible and more acceptable to patients, but the benefits of HBET compared to SET have not been consistently demonstrated in studies. Wearable activities monitor (WAM) have been proposed as an adjuvant to enhance the performance of HBET. However, there is no direct comparison of WAM enhanced HBET to SET. Furthermore, WAMs were mainly used for monitoring in HBET in the previous studies and patient feedback was conducted either in-person or over telephones by the researchers, which challenges the true meaning of HBET. In this study, we aim to evaluate the non-inferiority of personalized self-guided HBET enhanced with WAM and auto feedback mobile apps, to SET, in a randomized-controlled trial of patients with symptomatic PAD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
70
Supervised exercise therapy (SET) is a structured program of exercise designed for individuals with peripheral artery disease (PAD) and intermittent claudication (IC). It consists of 12 weeks of intermittent treadmill walking to moderate to severe claudication pain at a speed of ≈2 mph and at a grade equal to 40% of the highest workload achieved during the baseline maximal treadmill test, with intermittent period of rest, for at least 3 times per week with a minimum of 30-45 minutes per session
The WAM use in this study is the FitBit Inspire 3 Advanced Activity Tracker (FitBit Inc. San Francisco, CA, USA), which is a commercially available tri-axis accelerometer and heart rate monitor capable of continuous monitoring of heart rate using LED sensor, and activities including daily steps count and derived daily activity level, detection of arrythmia and measuring peripheral capillary oxygen saturation. Fitbit devices connect with HOBBIT-PAD platform which was developed specifically for patients with PAD based on user-centred design. It contains patient education information, instruction for exercise, activity record, and embedded messaging function between the patient and the research team about any technical and clinical issue. Important and thorough customizations will be made to tailor this mobile health platform for this study, which includes the addition of patient education materials on PAD and its management, tips on health eating and lifestyle, and tips on exercise.
Instructions for HBET are programmed according to the AHA recommendation on the exercise programs for patients with PAD and are automatically generated by the mobile apps. Patients will be prompted to use the exercise function on the mobile apps at least 3 times per week. Once the exercise function is activated, it will extract the steps counts and the walking pace from the WAM during exercise. Patients will be instructed to walk to maximal claudication symptom before stopping, at which point they will press pause on the WAM which will mark the claudication onset time. After the claudication subside, they can resume walking and resume recording on their WAM. Each exercise session will last for 45 minutes excluding rest periods, but the subject can terminate the exercise before the session ends.
The mobile apps and mobile platform are adopted from the HOBBIT-PAD platform prototype that was developed specifically for patients with PAD based on user-centred design. This platform contains patient education information, instruction for exercise, activity record, and embedded messaging function between the patient and the research team about any technical and clinical issue. The source code for this platform is publicly available. Important customization will be made to tailor this mobile health platform for this study, which includes addition of patient education materials on PAD and its management, tips on health eating and lifestyle, and tips on exercise. These materials are adopted from the patient education materials available on the Hospital Authority and the AHA website. This information will be periodically sent to the subject's mobile device as a push notification to help them better understand their disease and to promote independent self-care and healthy lifestyle.
Prince of Wales Hospital
Hong Kong, Hong Kong, Hong Kong
RECRUITINGPrince of Wales Hospital
Hong Kong, Shatin, Hong Kong
RECRUITINGChange in 6-minute walk test distance
The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance in meters covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity
Time frame: 12 weeks, 26 weeks
compliance to treatment
Compliance to exercise therapy will be measured as the percentage of participation in the SET session in the control arm, and percentage of exercise program activation in the intervention arm.
Time frame: 12 weeks, 26 weeks
change in claudication symptoms
claudication symptoms as measured by the Walking Impairment Questionnaire which was The WIQ is a short, validated questionnaire for patients with peripheral arterial disease that is easy to complete. It contains three domains to assess walking impairment: walking distance, walking speed, and stair climbing. For each domain, a sub-score of the Likert items was calculated. The mean of these domains represents the total WIQ score. The Chinese version of the WIQ has been validated by our centre against the claudication symptoms and showed to be a reliable and clinically relevant instrument
Time frame: 12 weeks, 26 weeks
change in quality of life
The 36-items short-form (SF-32) health survey score score will be converted to SF-6D index score which is a preference-based measure of health-related quality of life (HRQoL) for its descriptive ability. The SF-6D index score will be used in the subsequent cost-effectiveness analysis.
Time frame: 12 weeks, 26 weeks
change in endothelial function
endothelium function will be evaluated using the Flow-mediated dilatation (FMD). The test will be performed in a quiet, temperature-controlled room with the subject lying supine. Subjects are advised to refrain from ingesting caffeine, high-fat foods and vitamin C or use tobacco for at least 6 hours prior to the study. After a qualified image is acquired for analysis, a pressure cuff placed distal to the imaging probe at the forearm will be inflated to 50mmHg above the systolic pressure for 5 minutes. The longitudinal image of the brachial artery is scan continuous for 3 minutes after the deflation of the cuff. The percentage change in peak brachial artery diameter before and after the cuff inflation will be calculated automatically and reported as the FMD of the subject.
Time frame: 12 weeks, 26 weeks
change in arterial compliance
arterial compliance as measured by the carotid-femoral pulse-wave velocity which is is a well-validated surrogate measurement of arteria stiffness and is an important prognostic marker for future cardiovascular event39. Several previous studies have shown a reduction in cfPWV after a period of exercise training in non-PAD individuals. The Vicorder (software version 4; Skidmore Medical) which uses the oscillometric technique to acquire the pulse waveform, will be used for cfPWV measurement. Measurements of cfPWV will be obtained by using a 10-cm-wide cuff around the right upper thigh to detect the femoral pulse and a 3-cm cuff around the neck to detect the right carotid pulse. The distance between the suprasternal notch and mid upper thigh cuff is used as the travel distance between the carotid and the femoral cuff. The cfPWV is calculated automatically as cfPWV (m/s)=distance (m)/transit time (s)
Time frame: 12 weeks, 26 weeks
change in lower limb perfusion
lower limb perfusion as measured by Exercise ankle-brachial index (ABI) and Transcutaneous oxygen tension (TcPO2) .Exercise ABI will be performed using the Gardener progressive graded treadmill protocol (2mph, 0% grade with 2% increase every 2 minutes) until maximal claudication pain or for a maximum of 5 minutes. Immediately after exercise, the patient is asked to lie in a supine position and ABI test is repeated. The difference between the resting ABI and post exercise ABI reflects lower limb perfusion on exertion.
Time frame: 12 weeks, 26 weeks
change in calf muscle strength
The assessment of isometric muscle strength of the lower extremities will be assessed for knee extension, knee flexion, ankle plantarflexion, and ankle dorsiflexion. All tests will assess the muscle strength by the peak force and the rate of force development using a hand- held dynamometer (microFET2, Hoggan Scientific, Salt Lake City UT, USA) which has been shown to have excellent correlation with the criterion-reference dynamometers42. The presence of PAD significantly weakened lower extremity power43. However, the impact of exercise on muscle strength has not been definitively ascertained44
Time frame: 12 weeks, 26 weeks
change in blood inflammatory markers
Blood Tests for cardiovascular risk factors including Haemoglobin A1c as measured in percentage of glycated hemoglobin and lipid profile as measured in mmol/l will be sent to local laboratory for processing. Additional blood tests for high-sensitivity C- reactive protein (hs-CRP) as measured in mg/L, and interleukin-6 (IL-6) as measured in pg/ml will be sent to an accredited medical laboratory for processing as these parameters are not available as a routine blood test at the local laboratory.
Time frame: 12 weeks, 26 weeks
cost-effectiveness
Cost-effectiveness analysis will be carried out from a health-care payer perspective, and non health-care consequences such as effects on production loss or cost of transportation to the health-care facility will not be considered. The cost for each treatment will be calculated with reference to the gazetted price from the Hospital Authority. The current listed price for SET is HKD 2830, and the cost for eHBET involves only the WAM which is listed at HKD800. The incremental cost-effectiveness ratio (ICER) will be calculated using between group cost difference divided by difference in HRQoL. Following the World Health Organization's guidelines, we defined the willingness-to-pay (WTP) threshold as 1 times the local gross domestic product per capita (which is US $49,146= HKD 384,284 in 2021), and the treatment is considered cost-effective if the ICER of the treatment is lower than the WTP threshold.
Time frame: 12 weeks, 26 weeks
change in skin perfusion
TcPO2 measures the local oxygen released from the capillaries through the skin, reflecting the metabolic state of the lower limb. The reproducibility of TcPO2 is much higher than ABI therefore allowing for a detection of a relatively small changes in lower limb perfusion after any therapeutic intervention. TcPO2 will be measured using the Perimed Periflux System 6000 (Perimed Corporation, Stockholm, Sweden) with the patient lying supine in a well-lit and temperature-controlled room. Two electrodes whose membranes are maintained at 45°C are placed on the dorsum of the foot and equilibration will be allowed before taking any measurement.
Time frame: 12 weeks, 26 weeks
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