Protocols and Guidelines for the Use of Digital Twins in Frail Older People (Proto-Aging)

The Proto-Aging study aims to define experimental protocols and guidelines to enable the development of musculoskeletal models (digital twins) of elderly people, with the ultimate goal to comprehensively characterize frail elders from a biomechanical standpoint.

It is typical for the elderly to present with weakness, slowed movements and reduced levels of physical activity, all of which may be related to the loss of muscle force (dynapenia). Unfortunately, to date, the primary cause for dynapenia is difficult to identify. Digital twins may help to this end, but their development remains critical as it requires a specialized skillset and experimental data for model personalisation.

In this study, where the investigators will recruit a small group of frail elders and a cohort of healthy young individuals, all participants will undergo the following examinations: (i) gait assessment, (ii) maximal voluntary isometric contraction (MVIC) test, (iii) superimposed neuromuscular electrical stimulation, and (iv) full lower limb magnetic resonance imaging. Surface electromyography data will further be collected while the subjects perform both the gait assessment and the MVIC test. Last, clinical questionnaires will be administered, and the subjects will be asked to perform additional clinical measures (i.e., hand-grip test, bioelectrical impedance analysis).

At the end of the study, a reduced version of the experimental protocol will be developed, with the intent to provide clinicians with a protocol that can be deployed in clinical settings, accounting for the observed reliability and repeatability of each measure, the required level of expertise, and the associated costs and time expenditure.

Study Overview

• Status: Completed
• Conditions: Frail Elderly Syndrome
• Intervention / Treatment: Diagnostic test: Comprehensive Biomechanical assessment

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marco Viceconti, Professor; Phone Number: 578 +39 051.63.66; Email: marco.viceconti@ior.it
• Study Contact Backup: Name: Maria Grazia Benedetti, Professor; Phone Number: 236 +39 051.63.66; Email: mariagrazia.benedetti@ior.it

Study Locations

• Italy
  • Bologna, Italy, 40136
    • IRCCS Istituto Ortopedico Rizzoli

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age: 65-80 years
• Body Mass Index between 18.5 and 30 kg/m2
• Frailty syndrome diagnosed according to Fried's criteria (i.e., at least three of the following items: unintended loss of weight, weakness, self-reported exhaustion, slow walking speed, low level of physical activity)

Exclusion Criteria:

• Any musculoskeletal, neurological, rheumatic or tumoral diseases
• Dementia
• Diabetes
• Inguinal or abdominal hernia
• Severe Hypertension (Level 3)
• Severe Cardio-pulmonary insufficiency
• Diagnosis of Osteonecrosis in the lower limb joints
• Pathologies or physical conditions incompatible with the use of magnetic resonance imaging and electrostimulation (i.e., active and passive implanted biomedical devices, epilepsy, severe venous insufficiency in the lower limbs)
• Previous interventions or traumas to the joints of the lower limb

NOTE: A group of healthy volunteers, who meet the following criteria, will be enrolled in the study:

Inclusion Criteria:

• Age: 20-40 years;
• Body Mass Index: 15-30 kg/m²;
• Physical activity level (Saltin-Grimby): 2-4
• No previous or known musculoskeletal, neurological, rheumatic or tumoral diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Frail elders; Frail elders; Age: 65-80 years; Body Mass Index: 18.5-30 kg/m²; Frailty diagnosed according to Fried's criteria (i.e., at least three of the following items: unintended loss of weight, weakness, self-reported exhaustion, slow walking speed, low level of physical activity).	Diagnostic test: Comprehensive Biomechanical assessment; Magnetic resonance images, electromyography and dynamometry data will be used, together with data from the gait assessment and clinical questionnaires/measures, to characterize the biomechanics of the participants, and to develop and inform personalised musculoskeletal models

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle volume	Full lower limb MRI data will be acquired with subjects in supine position. Individual muscle volumes (in cm3) will be segmented using commercial software and stored in anonymized form.	at baseline (Day 0)
MVIC Torque	Dynamometry data will be acquired while participants perform a MVIC leg extension test. The maximum torque values (Nm) measured over three repetitions will be recorded. These correspond to the values observed in correspondence of the plateaux of force, developed over a sustained contraction	at baseline (Day 0)
Muscle Inhibition level	The difference between the maximal force exerted during the MVIC test (voluntary contraction) and that achieved when the muscles are electrically stimulated (involuntary contraction) will be computed	at baseline (Day 0)
Body kinematics	A standard gait assessment will be performed where motion capture data will be collected. Joint angles will be extracted to identify abnormal gait patterns.	at baseline (Day 0)
Co-contraction index (CCI)	Experimental EMG data will be recorded from the major lower limb muscles involved in the knee extension, while participants perform a maximal voluntary isometric contraction on a dynamometer (i.e., MVIC test to quantify muscle strength). The co-contraction index, defined as the relative activation of agonist and antagonist muscles (for this task: quadriceps and hamstrings) in the act of kicking (MVIC test).	at baseline (Day 0)

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Rizzoli
• Investigators: Principal Investigator: Maria Grazia Benedetti, Professor, IRCCS Istituto Ortopedico Rizzoli

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2023
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): July 27, 2023

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 11, 2023

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Elderly; Dynamometry; Electromyography; Frailty; Dynapenia; Muscle weakness; Maximal Voluntary Isometric Contraction; Superimposed Neuromuscular Electrical Stimulation; Clinical questionnaires; Hand-grip test
• Other Study ID Numbers: Proto-Aging

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No