Daily Activity Measured With Wearable Technology as a Novel Measurement of Treatment Effect in Patients With Coronary Microvascular Dysfunction: Substudy of a Randomized Controlled Crossover Trial.

• Type of Material: Article
• Authors: Kade Birkeland, Cedars-Sinai Medical Center, Los Angeles; Raj M Khandwalla, Cedars-Sinai Heart Institute; Ilan Kedan, Cedars-Sinai Heart Institute; Chrisandra L Shufelt, Cedars-Sinai Heart Institute; Puja Kiran Mehta, Emory University; Margo B Minissian, Cedars-Sinai Heart Institute; Janet Wei, Cedars-Sinai Heart Institute; Eileen M Handberg, University of Florida; Louise EJ Thomson, Cedars-Sinai Medical Center, Los Angeles; Daniel S Berman, Cedars-Sinai Medical Center, Los Angeles; John W Petersen, University of Florida; R David Anderson, University of Florida; Galen Cook-Wiens, Cedars-Sinai Medical Center, Los Angeles; Carl J. Pepine, University of Florida; C Noel Bairey Merz, Cedars-Sinai Heart Institute
• Language: English
• Date: 2017-12-20
• Publisher: JMIR Publications
• Publication Version: Final Published Version
• Copyright Statement: ©Kade Birkeland, Raj M Khandwalla, Ilan Kedan, Chrisandra L Shufelt, Puja K Mehta, Margo B Minissian, Janet Wei, Eileen M Handberg, Louise EJ Thomson, Daniel S Berman, John W Petersen, R David Anderson, Galen Cook-Wiens, Carl J Pepine, C Noel Bairey Merz.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.2196/resprot.8057
• Title of Journal or Parent Work: JMIR Research Protocols
• ISSN: 1929-0748
• Volume: 6
• Issue: 12
• Start Page: e255
• End Page: e255
• Grant/Funding Information: The parent trial was supported by an unrestricted research grant from Gilead and by contracts from the National Heart, Lung, and Blood Institutes (N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, K23HL105787, T32-HL-116273); a GCRC grant (MO1-RR00425) from the National Center for Research Resources; grant UL1RR033176 the NIH/National Center for Advancing Translational Sciences (NCATS); UCLA CTSI grant UL1TR000124; and UF CTSI grant UL1TR001427, grant R01 HL089765; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, NJ; the Women’s Guild of Cedars-Sinai Medical Center, Los Angeles, CA; the Edythe L Broad Women’s Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, CA; the Constance Austin Women’s Heart Research Fellowship; the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, CA; the Erika Glazer Women’s Heart Health Project, Cedars-Sinai Medical Center, Los Angeles, CA.; CJP was supported by NHLBI grants HL33610, HL56921, UM1 HL087366, and the Gatorade Trust through funds distributed by the University of Florida, Department of Medicine; the NIH NCATS-University of Florida Clinical and Translational Science UL1TR001427; and the PCORI-OneFlorida Clinical Research Consortium CDRN-1501-26692.; This pilot study was intramurally funded by the Cedars-Sinai Clinical and Translational Science Institute Clinical Scholars Program, Cedars-Sinai Medical Center, Los Angeles, CA.
• Keywords: coronary microvascular dysfunction; angina; physical activity
• Research Categories: Biology, Biostatistics; Biology, Bioinformatics; Health Sciences, Medicine and Surgery

Abstract

BACKGROUND: Digital wearable devices provide a "real-world" assessment of physical activity and quantify intervention-related changes in clinical trials. However, the value of digital wearable device-recorded physical activity as a clinical trial outcome is unknown. OBJECTIVE: Because late sodium channel inhibition (ranolazine) improves stress laboratory exercise duration among angina patients, we proposed that this benefit could be quantified and translated during daily life by measuring digital wearable device-determined step count in a clinical trial. METHODS: We conducted a substudy in a randomized, double-blinded, placebo-controlled, crossover trial of participants with angina and coronary microvascular dysfunction (CMD) with no obstructive coronary artery disease to evaluate the value of digital wearable device monitoring. Ranolazine or placebo were administered (500-1000 mg twice a day) for 2 weeks with a subsequent 2-week washout followed by crossover to ranolazine or placebo (500-1000 mg twice a day) for an additional 2 weeks. The outcome of interest was within-subject difference in Fitbit Flex daily step count during week 2 of ranolazine versus placebo during each treatment period. Secondary outcomes included within-subject differences in angina, quality of life, myocardial perfusion reserve, and diastolic function. RESULTS: A total of 43 participants were enrolled in the substudy and 30 successfully completed the substudy for analysis. Overall, late sodium channel inhibition reduced within-subject daily step count versus placebo (mean 5757 [SD 3076] vs mean 6593 [SD 339], P=.01) but did not improve angina (Seattle Angina Questionnaire-7 [SAQ-7]) (P=.83). Among the subgroup with improved angina (SAQ-7), a direct correlation with increased step count (r=.42, P=.02) was observed. CONCLUSIONS: We report one of the first studies to use digital wearable device-determined step count as an outcome variable in a placebo-controlled crossover trial of late sodium channel inhibition in participants with CMD. Our substudy demonstrates that late sodium channel inhibition was associated with a decreased step count overall, although the subgroup with angina improvement had a step count increase. Our findings suggest digital wearable device technology may provide new insights in clinical trial research. TRIAL REGISTRATION: Clinicaltrials.gov NCT01342029; https://clinicaltrials.gov/ct2/show/NCT01342029 (Archived by WebCite at http://www.webcitation.org/6uyd6B2PO).