TY - JOUR
T1 - Identifying responders to elamipretide in Barth syndrome
T2 - Hierarchical clustering for time series data
AU - Van den Eynde, Jef
AU - Chinni, Bhargava
AU - Vernon, Hilary
AU - Thompson, W. Reid
AU - Hornby, Brittany
AU - Kutty, Shelby
AU - Manlhiot, Cedric
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Background: Barth syndrome (BTHS) is a rare genetic disease that is characterized by cardiomyopathy, skeletal myopathy, neutropenia, and growth abnormalities and often leads to death in childhood. Recently, elamipretide has been tested as a potential first disease-modifying drug. This study aimed to identify patients with BTHS who may respond to elamipretide, based on continuous physiological measurements acquired through wearable devices. Results: Data from a randomized, double-blind, placebo-controlled crossover trial of 12 patients with BTHS were used, including physiological time series data measured using a wearable device (heart rate, respiratory rate, activity, and posture) and functional scores. The latter included the 6-minute walk test (6MWT), Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue score, SWAY Balance Mobile Application score (SWAY balance score), BTHS Symptom Assessment (BTHS-SA) Total Fatigue score, muscle strength by handheld dynamometry, 5 times sit-and-stand test (5XSST), and monolysocardiolipin to cardiolipin ratio (MLCL:CL). Groups were created through median split of the functional scores into “highest score” and “lowest score”, and “best response to elamipretide” and “worst response to elamipretide”. Agglomerative hierarchical clustering (AHC) models were implemented to assess whether physiological data could classify patients according to functional status and distinguish non-responders from responders to elamipretide. AHC models clustered patients according to their functional status with accuracies of 60–93%, with the greatest accuracies for 6MWT (93%), PROMIS (87%), and SWAY balance score (80%). Another set of AHC models clustered patients with respect to their response to treatment with elamipretide with perfect accuracy (all 100%). Conclusions: In this proof-of-concept study, we demonstrated that continuously acquired physiological measurements from wearable devices can be used to predict functional status and response to treatment among patients with BTHS.
AB - Background: Barth syndrome (BTHS) is a rare genetic disease that is characterized by cardiomyopathy, skeletal myopathy, neutropenia, and growth abnormalities and often leads to death in childhood. Recently, elamipretide has been tested as a potential first disease-modifying drug. This study aimed to identify patients with BTHS who may respond to elamipretide, based on continuous physiological measurements acquired through wearable devices. Results: Data from a randomized, double-blind, placebo-controlled crossover trial of 12 patients with BTHS were used, including physiological time series data measured using a wearable device (heart rate, respiratory rate, activity, and posture) and functional scores. The latter included the 6-minute walk test (6MWT), Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue score, SWAY Balance Mobile Application score (SWAY balance score), BTHS Symptom Assessment (BTHS-SA) Total Fatigue score, muscle strength by handheld dynamometry, 5 times sit-and-stand test (5XSST), and monolysocardiolipin to cardiolipin ratio (MLCL:CL). Groups were created through median split of the functional scores into “highest score” and “lowest score”, and “best response to elamipretide” and “worst response to elamipretide”. Agglomerative hierarchical clustering (AHC) models were implemented to assess whether physiological data could classify patients according to functional status and distinguish non-responders from responders to elamipretide. AHC models clustered patients according to their functional status with accuracies of 60–93%, with the greatest accuracies for 6MWT (93%), PROMIS (87%), and SWAY balance score (80%). Another set of AHC models clustered patients with respect to their response to treatment with elamipretide with perfect accuracy (all 100%). Conclusions: In this proof-of-concept study, we demonstrated that continuously acquired physiological measurements from wearable devices can be used to predict functional status and response to treatment among patients with BTHS.
KW - Barth syndrome
KW - Digital health
KW - Hierarchical clustering
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U2 - 10.1186/s13023-023-02676-8
DO - 10.1186/s13023-023-02676-8
M3 - Article
C2 - 37041653
AN - SCOPUS:85152255961
SN - 1750-1172
VL - 18
JO - Orphanet journal of rare diseases
JF - Orphanet journal of rare diseases
IS - 1
M1 - 76
ER -