Personalised Modeling and Simulations for the Differential Diagnosis of Dynapenia: Study on Patients With Osteoarthritis (ForceLoss II)

May 27, 2024 updated by: Istituto Ortopedico Rizzoli

ForceLoss: Part II - Osteoarthritic Patients. Development and Validation of Methods to Generate Personalised Models for the Differential Diagnosis of the Loss of Muscle Force

The ForceLoss study aims to develop personalised modeling and simulation procedures to enable the differential diagnosis for the loss of muscle force, namely dynapenia. The primary causes of dynapenia can be identified in a diffuse or selective sarcopenia, a lack of activation (inhibition), or suboptimal motor control. Each of these causes requires different interventions, but a reliable differential diagnosis is currently impossible. While biomedical instruments and tools can provide valuable information, it is often left to the experience of the single clinican to integrate such information into a complete diagnostic picture. An accurate diagnosis for dynapenia is important for a number of pathologies, including neurological diseases, age-related frailty, diabetes, and orthopaedic conditions.

The hypothesis is that the use of mechanistic, subject-specific models (digital twins) to simulate a maximal isometric knee extension task, informed by experimental measures may be employed to conduct a robust differential diagnosis for dynapenia.

In this study, on patients candidate for knee arthroplasty, the investigators will expand (i) the experimental protocol previously developed and tested on healthy volunteers with a measure of involuntary muscle contraction (superimposed neuromuscular electrical stimulation, SNMES), a hand-grip test, measures of bio-impedance and clinical questionnaires, and (ii) the modeling and simulation framework to include one additional step (to check for muscle inhibition).

Medical imaging, electromyography (EMG) and dynamometry data will be collected and combined to inform a digital twin of each participant. Biomechanical computer simulations of a Maximal Voluntary Isometric Contraction (MVIC) task will then be performed. Comparing the models' estimates to in vivo dynamometry measurements and EMG data, the investigators will test one by one the three possible causes of dynapenia, and, through a process of hypothesis falsification will exclude those that do not explain the observed loss of muscle force.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years to 80 years (Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of Primary Arthrosis at the knee (according to the American College of Rheumatology criteria), subjects elected for tota knee arthroplasty
  • Body Mass Index between 18.5 and 30 kg/m2
  • Health status (according to the American Society of Anesthesiology classification) equal to 1 or 2
  • Suspected systemic sarcopenia due to aging or localized sarcopenia due to disuse

Exclusion Criteria:

  • Neurological, rheumatic or tumoral diseases
  • Inguinal or abdominal hernia
  • Diabetes
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Knee Osteoarthritic Patients
Patients candidate for knee arthroplasty; Age: 65-80 years; Body Mass Index: 18.5-30 kg/m²; ASA Classification: 1 or 2; Diagnosis of primary osteoarthritis at the knee; Suspect sarcopenia.
Diagnostic test: Personalised Musculoskeletal Modeling
Magnetic resonance images, electromyography and dynamometry data will be used to develop and inform personalised musculoskeletal models
Other Names:
  • Clinical measures (BIA, Hand-grip test)
  • Clinical questionnaires (WOMAC, KSS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle volume
Time Frame: at baseline (Day 0)
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
Time Frame: at baseline (Day 0)
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
Time Frame: at baseline (Day 0)
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)
Co-contraction index (CCI)
Time Frame: at baseline (Day 0)

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), will be computed according to Li et al (2020).
at baseline (Day 0)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Ortopedico Rizzoli

Investigators

  • Principal Investigator: Marco Viceconti, Professor, IRCCS Istituto Ortopedico Rizzoli

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 28, 2023

Primary Completion (Actual)

May 27, 2024

Study Completion (Actual)

May 27, 2024

Study Registration Dates

First Submitted

March 21, 2023

First Submitted That Met QC Criteria

March 21, 2023

First Posted (Actual)

April 3, 2023

Study Record Updates

Last Update Posted (Actual)

May 29, 2024

Last Update Submitted That Met QC Criteria

May 27, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ForceLoss II

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We plan to share a database of experimental data representative of a population of patients elected for total knee arthroplasty. The dataset will include torques profiles and EMG data recorded during the MVIC test, the torque profiles recorded while delivering the electrical stimulation, and may include processed Magnetic Resonance Imaging data (segmentations of lower limb bones bones and muscles). All data will be irreversibly anonymized.

IPD Sharing Time Frame

The (anonymized) dataset will be made available to the wider biomechanical community upon study completion

IPD Sharing Access Criteria

Not yet defined

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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