Utility of At-home Monitoring of Exercise Capacity by App-based 6-minute Walk Test

Study Overview
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Brief Summary
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Evaluate for accuracy and reproducibility of data collected via the participant-operated Walk.Talk.Track. (WTT) app combined with Apple Watch during in-clinic, technician proctored 6MWT's. Determine whether the WTT app on the Apple Watch can accurately collect information on distance traveled and heart rate (HR) during in-clinic 6MWT run by American Thoracic Society (ATS) guidelines Determine whether participants can operate the WTT app and Apple Watch effectively to gather accurate data in a monitored and home-based setting Prospectively monitor for changes in WTT app recorded 6MWT results following initiation of therapy in a treatment naïve cohort of PAH participants Evaluate whether changes from baseline in 6 minute walk distance (6MWD) and heart rate recovery at one minute (HRR1) as well as other variables that have been associated with disease severity in PAH and left-sided heart disease (resting HR, heart rate variability [HRV], chronotropic index [CI]) can be identified before the 12-week follow up when comparing the treatment arm and the control arm Evaluate whether changes from baseline in the HRR1, resting HR, HRV and/or CI are more evident in treatment responders when compared to treatment non-responders.

Official Title
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Utility of Device and App-based Mobile Health Monitoring as a Tool for Evaluation of Clinical Response to Therapies in Pulmonary Arterial Hypertension

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Device: Home-based 6 minute walk test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of WHO Group I Pulmonary Arterial Hypertension (PAH) (Idiopathic (I)PAH, Heritable PAH (including Hereditary Hemorrhagic Telangiectasia), Associated (A)PAH (including collagen vascular disorders, drugs+toxins exposure, congenital heart disease, and portopulmonary disease). Do not meet exclusion criteria Exclusion Criteria: Pulmonary Hypertension due to left heart disease (PH-LHD, WHO group 2), Pulmonary hypertension due to chronic lung disease (PH-CLD, WHO group 3), Chronic thrombo-embolic pulmonary hypertension (CTEPH, WHO group 4), pulmonary hypertension with unclear and/or multi-factorial mechanisms (WHO goup 5) Inability to perform a 6 minute walk test (6MWT)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Initiating a new PAH medication<br>Participants will start a new PAH medication | Device: Home-based 6 minute walk test<br>* Participants will receive a loaner Apple Watch with the Walk.Talk.Track. (WTT, produced by PHaware) app downloaded. Participants will perform a daily 6MWT at home using the Apple Watch and WTT app. They will undergo a history and physical, blood draw, echocardiogram and in-clinic 6MWT at the baseline and 12-week follow up visit.<br>|
| Active Comparator: Continuing previous PAH medication regimen<br>Participants will continue the medication regimen that they were on prior to enrollment | Device: Home-based 6 minute walk test<br>* Participants will receive a loaner Apple Watch with the Walk.Talk.Track. (WTT, produced by PHaware) app downloaded. Participants will perform a daily 6MWT at home using the Apple Watch and WTT app. They will undergo a history and physical, blood draw, echocardiogram and in-clinic 6MWT at the baseline and 12-week follow up visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| App/watch recorded and in-clinic recorded six minute walk distance (6MWD) | App/watch recorded and in-clinic recorded 6MWD will be compared by Bland Altman graph and will be considered interchangeable if the line of equality lands within the 95% confidence interval of the mean difference | 12 weeks | 
| Count of participants with an increase of >32 meters in 6MWD from baseline as a measure of time to response to therapy | Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 
| Count of participants with an increase of >3bpm in heart rate recovery at one minute (HRR1) from baseline as a measure of time to response to therapy | HRR1 is calculated as peak heart rate (pHR) - HR one minute into recovery period. Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of participants with a decrease of >5bpm in resting HR from baseline as a measure of time to response to therapy | Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 
| Count of participants with an increase of >5ms in heart rate variability (HRV) from baseline as a measure of time to response to therapy | HRV will be calculated as the standard deviation of R wave to R wave intervals (SDNN) over the 2 minute period following exercise. Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 
| Count of participants with an increase of >5% in chronotropic index (CI) from baseline as a measure of time to response to therapy | CI will be calculated as (actual peak HR - resting HR)/(Age predicted peak HR [220-age] - resting HR). Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 
| Within the treatment arm, count of participants with an increase of >3bpm in heart rate recovery at one minute (HRR1) from baseline when comparing medication responders vs non-responders | Medication responders will have a ≥32m improvement in 6MWD at 12 weeks; non-responders will have <32m improvement. Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 
| Within the treatment arm, count of participants with a decrease of >5bpm in resting HR from baseline when comparing medication responders vs non-responders | Medication responders will have a ≥32m improvement in 6MWD at 12 weeks; non-responders will have <32m improvement. Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 
| Within the treatment arm, count of participants with an increase of >5ms in heart rate variability (HRV) from baseline when comparing medication responders vs non-responders | Medication responders will have a ≥32m improvement in 6MWD at 12 weeks; non-responders will have <32m improvement. Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 
| Within the treatment arm, count of participants with an increase of >5% in chronotropic index (CI) from baseline when comparing medication responders vs non-responders | Medication responders will have a ≥32m improvement in 6MWD at 12 weeks; non-responders will have <32m improvement. Hazard ratios will be calculated at two week intervals to evaluate for between group differences | 12 weeks | 
| Between group difference in 6MWD as a measure of response to the intervention | A two-sample T-test will be performed on the delta change in 6MWD (week 12 - baseline / baseline) x100]) between the treatment and control groups and a p-value will be calculated from this data. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Six minute walk test, Six minute walk distance, Heart rate recovery, Mobile health