Morphological and Functional Biomarkers of Skeletal Muscle Adaptations in Sarcopenia

Official title

Morphological and Functional Biomarkers of Skeletal Muscle Adaptations for Early Detection of Sarcopenia and of the Therapeutic Effects of a Home-Based Exercise Intervention: A Randomized-Controlled Trial

Overview

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.

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 plat
• 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 interventi

Primary outcome measures

• Change in 30-second Chair Stand Test performance [Time frame: Baseline, Week 12, and Week 48]

Secondary outcome measures (12)

• Change in handgrip strength [Time frame: Baseline, Week 12, and Week 48]
• Change in lower-limb explosive strength [Time frame: Baseline, Week 12, and Week 48]
• Change in 6-Minute Walk Test distance [Time frame: Baseline, Week 12, and Week 48]
• Change in Mini-Balance Evaluation Systems Test score [Time frame: Baseline, Week 12, and Week 48]
• Change in fat mass assessed by bioelectrical impedance analysis [Time frame: Fat mass will be assessed using bioelectrical impedance analysis according to standardized procedures. The outcome will be expressed in percentage. Changes from baseline to Week 12 and Week 48 will be evaluated.]
• Change in lean mass assessed by bioelectrical impedance analysis [Time frame: Baseline, Week 12, and Week 48]
• Change in skeletal muscle mass index assessed by bioelectrical impedance analysis [Time frame: Baseline, Week 12, and Week 48]
• Change in appendicular skeletal muscle mass index assessed by dual-energy X-ray absorptiometry [Time frame: Baseline and Week 48]
• Change in quantitative ultrasound radio-frequency-derived muscle echo-intensity parameters [Time frame: Baseline, Week 12, and Week 48]
• Area under the receiver operating characteristic curve of quantitative ultrasound radio-frequency analysis for sarcopenia classification [Time frame: Baseline]
• Change in 12-Item Short Form Health Survey Physical Component Summary score [Time frame: Baseline, Week 12, and Week 48]
• Change in 12-Item Short Form Health Survey Mental Component Summary score [Time frame: Baseline, Week 12, and Week 48]

Eligibility criteria

Inclusion criteria

• Sedentary individuals aged over 50 years.
• Individuals with sarcopenia, defined as reduced muscle mass assessed by bioelectrical impedance analysis and reduced muscle strength assessed by handgrip strength, according to EWGSOP2 criteria.
• Individuals at risk of sarcopenia, defined as reduced muscle mass with preserved muscle strength.
• Healthy age-, sex-, and physical activity-matched older adults eligible for inclusion in the reference cohort.
• Ability to understand the study procedures and provide written informed consent.

Exclusion criteria

• Hospitalization within the previous 6 weeks.
• Substance or alcohol abuse.
• Use of medications that may impair balance or coordination.
• Major locomotor impairments.
• Inability to complete the exercise protocol.
• Medical, cognitive, or functional conditions that, in the opinion of the investigators, may interfere with safe participation, adherence to the study procedures, or completion of the follow-up assessments.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 1 center

• IRCCS Ospedale Galeazzi-Sant'Ambrogio — Milan

Identifiers

NCT: NCT07692308 · GR-2024-12378411

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗