Morphological and Functional Biomarkers of Skeletal Muscle Adaptations in Sarcopenia

Summary

Sarcopenia is an age-related condition characterized by progressive loss of skeletal muscle mass, muscle strength, and physical performance. It is associated with frailty, falls, disability, reduced independence, lower quality of life, and increased healthcare burden. Despite its clinical relevance, sarcopenia remains underdiagnosed, partly because current diagnostic approaches may be difficult to implement broadly in clinical practice and may not fully capture early changes in muscle quality and neuromuscular function.

The EXEDOS study aims to evaluate an integrated diagnostic and therapeutic strategy for the early detection and management of sarcopenia. The study will assess Quantitative Ultrasound with Radio-Frequency analysis (QUS-RF) as a non-invasive, accessible, and radiation-free tool to characterize muscle morphology, microstructure, and quality. QUS-RF-derived parameters will be compared with established assessments, including body composition, muscle strength, physical performance, and imaging-based measures, to determine their feasibility, reliability, diagnostic accuracy, and responsiveness to change.

The study also includes a 48-week randomized, parallel-group, open-label superiority trial designed to evaluate the effects of a digitally delivered home-based exercise intervention in older adults with sarcopenia or at risk of sarcopenia. Eligible participants will be randomized to either an experimental group receiving a structured home-based exercise program or a control group receiving general physical activity recommendations in line with current guidelines. The exercise program will combine progressive resistance and aerobic training and will be supported by a digital platform allowing remote monitoring, feedback, and supervision. All participants will receive general nutritional advice.

Assessments will be performed at baseline, Week 12, and Week 48. The primary outcome of the randomized trial will be the change in 30-second Chair Stand Test performance, used as an indicator of lower-limb muscle function. Secondary outcomes will include handgrip strength, lower-limb maximal and explosive strength, walking capacity, balance, body composition, QUS-RF-derived muscle parameters, quality of life, mood, physical activity, dietary indicators, blood biomarkers, adherence to the intervention, and safety. A health economic analysis will also be conducted to estimate the potential cost-effectiveness and cost-utility of the proposed diagnostic and therapeutic strategy.

By combining innovative muscle assessment with a scalable digitally supported exercise intervention, the EXEDOS study aims to improve early sarcopenia detection, personalize exercise prescription, and support the development of sustainable strategies to preserve muscle function and independence in older adults.

Conditions

• Sarcopenia

Interventions

BEHAVIORAL

Digitally delivered home-based exercise intervention

Digitally delivered, home-based, 48-week exercise program combining progressive resistance training and moderate-intensity aerobic training. Participants will perform three sessions per week, each lasting approximately 45 minutes. Resistance exercises will use body weight and/or light external loads and will follow progressive overload principles. Aerobic exercise intensity will be adjusted using heart-rate feedback. The intervention will be delivered through a certified digital therapeutic platform including instructional videos, wearable inertial sensors, heart-rate monitoring, automated feedback, and remote professional supervision through chat or video call. Training progression will be individualized using adherence data, functional assessments, and monitoring outputs.

BEHAVIORAL

General physical activity recommendations

Participants allocated to the control condition will receive general physical activity recommendations in line with current WHO guidelines and general nutritional advice. They will not receive the digitally delivered individualized exercise program, wearable sensor-based monitoring, automated feedback, or remote exercise supervision. This intervention is intended to represent a standard recommendation-based comparator condition against which the digitally delivered home-based exercise intervention will be evaluated.

Sponsors & Collaborators

• Universita di Verona

  collaborator OTHER

• I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-06-03

Primary Completion

2027-06-03

Completion

2029-06-03

Countries

• Italy

Study Locations