Development of continuous assessment of muscle quality and frailty in older subjects using multi-parametric omics based on combined ultrasound and blood biomarkers: a study protocol for a cluster randomised controlled trial
Authors: Virto Naiara , Río Xabier , Angulo Garazi , García Rafael , Céspedes Almudena Avendaño , Zamora Elisa Belen Cortes , Jiménez Elena Gómez , Alcantud Ruben , Abizanda Pedro , Mañas Leocadio Rodriguez , Costa Alba , Matheu Ander , Lazcano Uxue , Vergara Itziar , Arjona Laura , Saeteros Morelva , Coca Aitor , Sanabria Sergio 
Published: April 2023

Background
Frailty derived from muscle quality loss can potentially be delayed through early detection and physical exercise interventions. There is a need for affordable tools for the objective evaluation of muscle quality, in both cross-sectional and longitudinal assessment. Literature suggests that quantitative analysis of ultrasound data captures morphometric, compositional and microstructural muscle properties, while biological essays derived from blood samples are associated with functional information. The aim of this study is to evaluate multi-parametric combinations of ultrasound and blood-based biomarkers to provide a cross-sectional evaluation of the patient frailty phenotype and to monitor muscle quality changes associated with supervised exercise programs.
Methods
This is a prospective observational multi-center study including patients older than 70 years with ability to give informed consent. We will recruit 100 patients from hospital environments and 100 from primary care facilities. At least two exams per patient (baseline and follow-up), with a total of (400 > 300) exams. In the hospital environments, 50 patients will be measured pre/post a 16-week individualized and supervised exercise programme, and 50 patients will be followed-up after the same period without intervention. The primary care patients will undergo a one-year follow-up evaluation. The primary goal is to compare cross-sectional evaluations of physical performance, functional capacity, body composition and derived scales of sarcopenia and frailty with biomarker combinations obtained from muscle ultrasound and blood-based essays. We will analyze ultrasound raw data obtained with a point-of-care device, and a set of biomarkers previously associated with frailty by quantitative Real time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Secondly, we will analyze the sensitivity of these biomarkers to detect short-term muscle quality changes as well as functional improvement after a supervised exercise intervention with respect to usual care.
Discussion
The presented study protocol will combine portable technologies based on quantitative muscle ultrasound and blood biomarkers for objective cross-sectional assessment of muscle quality in both hospital and primary care settings. It aims to provide data to investigate associations between biomarker combinations with cross-sectional clinical assessment of frailty and sarcopenia, as well as musculoskeletal changes after multicomponent physical exercise programs.
Trial Registration
ClinicalTrials.gov Identifier: NCT05294757. Date recorded: 24/03/2022. 'retrospectively registered’