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

Pulmonary Arterial Hypertension Clinical Trial

— DynAMITE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03893500
• Other study ID #: SU-DynAMITE
• Secondary ID: IRB-48742
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2024
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

• 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 63
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Device:
• Home-based 6 minute walk test
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.

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	PHaware

Country where clinical trial is conducted

United States, 

References & Publications (17)

Azarbal B, Hayes SW, Lewin HC, Hachamovitch R, Cohen I, Berman DS. The incremental prognostic value of percentage of heart rate reserve achieved over myocardial perfusion single-photon emission computed tomography in the prediction of cardiac death and all-cause mortality: superiority over 85% of maximal age-predicted heart rate. J Am Coll Cardiol. 2004 Jul 21;44(2):423-30. doi: 10.1016/j.jacc.2004.02.060. — View Citation

Cole CR, Blackstone EH, Pashkow FJ, Snader CE, Lauer MS. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med. 1999 Oct 28;341(18):1351-7. doi: 10.1056/NEJM199910283411804. — View Citation

Dobre D, Zannad F, Keteyian SJ, Stevens SR, Rossignol P, Kitzman DW, Landzberg J, Howlett J, Kraus WE, Ellis SJ. Association between resting heart rate, chronotropic index, and long-term outcomes in patients with heart failure receiving beta-blocker therapy: data from the HF-ACTION trial. Eur Heart J. 2013 Aug;34(29):2271-80. doi: 10.1093/eurheartj/ehs433. Epub 2013 Jan 12. — View Citation

Enright PL, Sherrill DL. Reference equations for the six-minute walk in healthy adults. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1384-7. doi: 10.1164/ajrccm.158.5.9710086. Erratum In: Am J Respir Crit Care Med. 2020 Feb 1;201(3):393. — View Citation

Girotra S, Kitzman DW, Kop WJ, Stein PK, Gottdiener JS, Mukamal KJ. Heart rate response to a timed walk and cardiovascular outcomes in older adults: the cardiovascular health study. Cardiology. 2012;122(2):69-75. doi: 10.1159/000338736. Epub 2012 Jun 20. — View Citation

Hoeper MM, Kramer T, Pan Z, Eichstaedt CA, Spiesshoefer J, Benjamin N, Olsson KM, Meyer K, Vizza CD, Vonk-Noordegraaf A, Distler O, Opitz C, Gibbs JSR, Delcroix M, Ghofrani HA, Huscher D, Pittrow D, Rosenkranz S, Grunig E. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017 Aug 3;50(2):1700740. doi: 10.1183/13993003.00740-2017. Print 2017 Aug. — View Citation

Huang RY, Dung LR. Measurement of heart rate variability using off-the-shelf smart phones. Biomed Eng Online. 2016 Jan 29;15:11. doi: 10.1186/s12938-016-0127-8. — View Citation

Latus H, Bandorski D, Rink F, Tiede H, Siaplaouras J, Ghofrani A, Seeger W, Schranz D, Apitz C. Heart Rate Variability is Related to Disease Severity in Children and Young Adults with Pulmonary Hypertension. Front Pediatr. 2015 Jul 7;3:63. doi: 10.3389/fped.2015.00063. eCollection 2015. — View Citation

Lauer MS, Francis GS, Okin PM, Pashkow FJ, Snader CE, Marwick TH. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA. 1999 Feb 10;281(6):524-9. doi: 10.1001/jama.281.6.524. — View Citation

Nogic J, Thein PM, Cameron J, Mirzaee S, Ihdayhid A, Nasis A. The utility of personal activity trackers (Fitbit Charge 2) on exercise capacity in patients post acute coronary syndrome [UP-STEP ACS Trial]: a randomised controlled trial protocol. BMC Cardiovasc Disord. 2017 Dec 29;17(1):303. doi: 10.1186/s12872-017-0726-8. — View Citation

Provencher S, Chemla D, Herve P, Sitbon O, Humbert M, Simonneau G. Heart rate responses during the 6-minute walk test in pulmonary arterial hypertension. Eur Respir J. 2006 Jan;27(1):114-20. doi: 10.1183/09031936.06.00042705. — View Citation

Ramos RP, Arakaki JS, Barbosa P, Treptow E, Valois FM, Ferreira EV, Nery LE, Neder JA. Heart rate recovery in pulmonary arterial hypertension: relationship with exercise capacity and prognosis. Am Heart J. 2012 Apr;163(4):580-8. doi: 10.1016/j.ahj.2012.01.023. Epub 2012 Mar 30. — View Citation

Swigris JJ, Olson AL, Shlobin OA, Ahmad S, Brown KK, Nathan SD. Heart rate recovery after six-minute walk test predicts pulmonary hypertension in patients with idiopathic pulmonary fibrosis. Respirology. 2011 Apr;16(3):439-45. doi: 10.1111/j.1440-1843.2010.01877.x. — View Citation

Tonelli AR, Wang XF, Alkukhun L, Zhang Q, Dweik RA, Minai OA. Heart rate slopes during 6-min walk test in pulmonary arterial hypertension, other lung diseases, and healthy controls. Physiol Rep. 2014 Jun 11;2(6):e12038. doi: 10.14814/phy2.12038. Print 2014 Jun 1. — View Citation

Wallen MP, Gomersall SR, Keating SE, Wisloff U, Coombes JS. Accuracy of Heart Rate Watches: Implications for Weight Management. PLoS One. 2016 May 27;11(5):e0154420. doi: 10.1371/journal.pone.0154420. eCollection 2016. — View Citation

Weatherald J, Boucly A, Sahay S, Humbert M, Sitbon O. The Low-Risk Profile in Pulmonary Arterial Hypertension. Time for a Paradigm Shift to Goal-oriented Clinical Trial Endpoints? Am J Respir Crit Care Med. 2018 Apr 1;197(7):860-868. doi: 10.1164/rccm.201709-1840PP. No abstract available. — View Citation

Zoller D, Siaplaouras J, Apitz A, Bride P, Kaestner M, Latus H, Schranz D, Apitz C. Home Exercise Training in Children and Adolescents with Pulmonary Arterial Hypertension: A Pilot Study. Pediatr Cardiol. 2017 Jan;38(1):191-198. doi: 10.1007/s00246-016-1501-9. Epub 2016 Nov 14. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   ATS guidelines for the 6 minute walk test