Development of Continuous Assessment of Muscle Quality and Frailty in Older Patients Using Multiparametric Combinations of Ultrasound and Blood Biomarkers: Protocol for the ECOFRAIL Study

Abstract

Background: Frailty resulting from the loss of muscle quality can potentially be delayed through early detection and physical exercise interventions. There is a demand for cost-effective tools for the objective evaluation of muscle quality, in both cross-sectional and longitudinal assessments. Literature suggests that quantitative analysis of ultrasound data captures morphometric, compositional, and microstructural muscle properties, while biological assays derived from blood samples are associated with functional information.

Objective: This study aims to assess multiparametric combinations of ultrasound and blood-based biomarkers to offer a cross-sectional evaluation of the patient frailty phenotype and to track changes in muscle quality associated with supervised exercise programs.

Methods: This prospective observational multicenter study will include patients aged 70 years and older who are capable of providing informed consent. We aim to recruit 100 patients from hospital environments and 100 from primary care facilities. Each patient will undergo at least two examinations (baseline and follow-up), totaling a minimum of 400 examinations. In hospital environments, 50 patients will be measured before/after a 16-week individualized and supervised exercise program, while another 50 patients will be followed up after the same period without intervention. Primary care patients will undergo a 1-year follow-up evaluation. The primary objective 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 assays. We will analyze ultrasound raw data obtained with a point-of-care device, along with a set of biomarkers previously associated with frailty, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Additionally, we will examine the sensitivity of these biomarkers to detect short-term muscle quality changes and functional improvement after a supervised exercise intervention compared with usual care.

Results: At the time of manuscript submission, the enrollment of volunteers is ongoing. Recruitment started on March 1, 2022, and ends on June 30, 2024.

Conclusions: The outlined study protocol will integrate portable technologies, using quantitative muscle ultrasound and blood biomarkers, to facilitate an objective cross-sectional assessment of muscle quality in both hospital and primary care settings. The primary objective is to generate data that can be used to explore associations between biomarker combinations and the cross-sectional clinical assessment of frailty and sarcopenia. Additionally, the study aims to investigate musculoskeletal changes following multicomponent physical exercise programs.

Trial registration: ClinicalTrials.gov NCT05294757; https://clinicaltrials.gov/ct2/show/NCT05294757.

International registered report identifier (irrid): DERR1-10.2196/50325.

Keywords: blood-based biomarkers; frailty; muscle; older adults; sarcopenia; ultrasound.

Figure 1

SPIRIT (Standard Protocol Items of the Recommendations for Interventional Trials) figure.

Figure 2

Flow diagram of the study protocol.

Figure 3

Ultrasound data flow and management from clinical acquisition centers to ultrasound data evaluation center.

Figure 4

Echographic B-mode appearance of mid-thigh in the (A) transverse and (B) longitudinal views.

Figure 5

Morphometric ultrasound measurements. (A) Rectus femoris thickness, cross-sectional surface, and perimeter (transverse view). (B) Pennation angle (longitudinal view).

Figure 6

Biomarkers data flow and management from clinical centers to blood-essay evaluation center. ELISA: enzyme-linked immunosorbent assay; qRT-PCR: real-time quantitative reverse transcription polymerase chain reaction.