Development of Continuous Assessment of Frailty and Muscle Quality in Older Subjects: ECOFRAIL Protocol (ECOFRAIL)

Development of Continuous Assessment of Muscle Quality and Frailty in Older Subjects Using Multi-parametric Combinations of Ultrasound and Blood Biomarkers: a Study Protocol for a Quasi-experimental Multi-center Study (ECOFRAIL Study)

We are conducting a study in different centers in Spain in elderly people, in order to assess the effectiveness of a physical exercise intervention program in people in a situation of frailty. Frailty in an elderly person is a situation in which, although there are no major differences in their usual abilities, the person presents a certain decrease in their capacities. This slight decrease is usually accompanied by a progressive deterioration.

Study Overview

• Status: Completed
• Conditions: Frailty; Exercise; Sarcopenia; Ultrasonography
• Intervention / Treatment: Other: Physical exercise

Detailed Description

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 (with a minimum total of 400 exams) 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.

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Donostia / San Sebastian, Spain
    • Donostialdea, Osakidetza
  • Getafe, Spain
    • Hospital Universitario de Getafe
  • Castille-La Mancha
    • Albacete, Castille-La Mancha, Spain, 02006
      • Complejo Hospitalario Universitario de Albacete

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age of at least 70 years old.
2. Either gender.
3. Ability to provide informed consent.
4. Ability to perform all the functional tests.
5. In the hospital exercise cohort, ability to perform the physical exercise program.

Exclusion Criteria:

1. Expected survival inferior to one year.
2. Barthel scale < 70.
3. Moderate to severe cognitive impairment.
4. Refuse to participate.
5. Medical conditions that may condition or difficult the follow-up assessments.
6. Older adults already included in regular physical exercise programmes will be excluded to participate in the hospital exercise cohort.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise; Elderly people without muscle problems participating in the exercise program to see improvements in their muscle mass levels and quality	Other: Physical exercise; 1. Hospital exercise cohort: Participants will be consecutively recruited from the scheduled patient list of the falls unit and the outpatient clinics of Hospital 1. After informed consent acquisition, patients will receive a baseline clinical evaluation. Ultrasound measurements and DXA scan will be conducted, and blood samples will be collected, processed, and stored. Patients will be included in the 16-week multicomponent physical exercise program described below. After the completion of the exercise program, at 16-week follow-up, clinical evaluation, ultrasound, DXA, and blood-sample testing will be repeated.
No Intervention: Hospital control; Hospital control cohort: Participants will be consecutively recruited from the scheduled patient list of the frailty unit, day hospital, and the outpatient clinic of the Geriatrics Department of Hospital 2. After obtaining informed consent, baseline study variables will be collected. Patients will be followed-up for a 16-week period, under usual care. After the follow-up period, baseline evaluation will be repeated.
No Intervention: Primary care Control; Primary care cohort: Participants will be consecutively recruited from the scheduled patient list of the Primary Care Units. After informed consent acquisition, baseline study variables will be collected. Patients will be followed-up during one year, under usual care. After the one-year follow-up, the baseline evaluation will be repeated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker - Quality of Life - Muscle mass	Association between quantitative ultrasound biomarkers associated to muscle mass and quality and extracted from raw data and blood-based biomarkers and combinations thereof with clinical variables including frailty, sarcopenia, physical function, disability, nutritional status, body composition, and Quality of Life in three cohorts of older adults: hospital control cohort, hospital exercise cohort, and primary care cohort. Muscle quality and mass: Ultrasound. Thickness (mm), cross-sectional area (cm²), perimeter (mm) and pennation angle (°). Frailty: FRAIL scale range 0-5. Frailty phenotype (0-5). Sarcopenia: SARC-F scale (0-10). Disability: GDS, 7 stages. Barthel index (0-100). Lawton and Brody index 0-8. Physical function: SPPB (0-12). IPAQ (0-3). Gait speed test, seconds. Grip strength, Jamar dynamometer, kilograms. Quality of life: EQ 5D-5L, scale of 0-100. Blood biomarkers: Vitamin D, Lutein zeaxanthin, Troponin T, Pro-BNP, and sRAGE with ELISA, miRNAs (qRT-PCR).	2 years

Collaborators and Investigators

• Sponsor: University of Deusto
• Collaborators: Complejo Hospitalario Universitario de Albacete; Hospital Universitario Getafe; European University of Vitoria-Gasteiz; Biogipuzkoa Health Research Institute
• Investigators: Principal Investigator: Sergio Sanabria, Ph.D., University of Deusto

Publications and helpful links

General Publications

• Virto N, Rio X, Angulo-Garay G, Garcia Molina R, Avendano Cespedes A, Cortes Zamora EB, Gomez Jimenez E, Alcantud Corcoles R, Rodriguez Manas L, Costa-Grille A, Matheu A, Marcos-Perez D, Lazcano U, Vergara I, Arjona L, Saeteros M, Lopez-de-Ipina D, Coca A, Abizanda Soler P, Sanabria SJ. 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. JMIR Res Protoc. 2024 Feb 23;13:e50325. doi: 10.2196/50325.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; Biomarkers; Diagnostic; Muscle; Echography
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathologic Processes; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Frailty; Disease; Sarcopenia; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: ECOFRAIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No