Osteoarthritis, KneeForceLoss IINCT05795348
Personalised Modeling and Simulations for the Differential Diagnosis of Dynapenia: Study on Patients With Osteoarthritis
A study testing Personalised Musculoskeletal Modeling in people with Osteoarthritis, Knee, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 65 to 80 years
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- Personalised Musculoskeletal Modeling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 28 Mar 2023to 27 May 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 80 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
- Conditions
- Osteoarthritis, Knee
- Being tested
- Personalised Musculoskeletal Modeling
- Keywords
- Dynapenia, Osteoarthritic patients, In Silico Medicine, Digital Twins, Maximal Voluntary Isometric Contraction, Musculoskeletal Modeling, Dynamometry, Electromyography, Superimposed Neuromuscular Electrical Stimulation
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Personalised Musculoskeletal ModelingDiagnostic test
Also called Clinical measures (BIA, Hand-grip test), Clinical questionnaires (WOMAC, KSS)
Magnetic resonance images, electromyography and dynamometry data will be used to develop and inform personalised musculoskeletal models
| Study group | Role | What they receive |
|---|---|---|
| Knee Osteoarthritic Patients | Other | 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. Receives: Diagnostic Test: Personalised Musculoskeletal Modeling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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), will be computed according to Li et al (2020).
Measured: at baseline (Day 0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2023
- Study start28 Mar 2023
- Primary completion27 May 2024
- Study completion27 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- More trials run by Istituto Ortopedico RizzoliThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Ortopedico Rizzoli
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marco Viceconti, Professor, Principal investigator, IRCCS Istituto Ortopedico Rizzoli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05795348
- Sponsor's protocol ID
- ForceLoss II
- Acronym
- ForceLoss II
- Status last verified
- May 2024
- First submitted
- 21 Mar 2023
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Fernandez J, Zhang J, Heidlauf T, Sartori M, Besier T, Rohrle O, Lloyd D. Multiscale musculoskeletal modelling, data-model fusion and electromyography-informed modelling. Interface Focus. 2016 Apr 6;6(2):20150084. doi: 10.1098/rsfs.2015.0084.
PubMed 27051510Hermens HJ, Freriks B, Disselhorst-Klug C, Rau G. Development of recommendations for SEMG sensors and sensor placement procedures. J Electromyogr Kinesiol. 2000 Oct;10(5):361-74. doi: 10.1016/s1050-6411(00)00027-4.
PubMed 11018445Petterson SC, Barrance P, Buchanan T, Binder-Macleod S, Snyder-Mackler L. Mechanisms underlying quadriceps weakness in knee osteoarthritis. Med Sci Sports Exerc. 2008 Mar;40(3):422-7. doi: 10.1249/MSS.0b013e31815ef285.
PubMed 18379202Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms and treatment perspectives. Semin Arthritis Rheum. 2010 Dec;40(3):250-66. doi: 10.1016/j.semarthrit.2009.10.001. Epub 2009 Dec 2.
PubMed 19954822Pons C, Borotikar B, Garetier M, Burdin V, Ben Salem D, Lempereur M, Brochard S. Quantifying skeletal muscle volume and shape in humans using MRI: A systematic review of validity and reliability. PLoS One. 2018 Nov 29;13(11):e0207847. doi: 10.1371/journal.pone.0207847. eCollection 2018.
PubMed 30496308Manini TM, Clark BC. Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci. 2012 Jan;67(1):28-40. doi: 10.1093/gerona/glr010. Epub 2011 Mar 28.
PubMed 21444359O'Brien TD, Reeves ND, Baltzopoulos V, Jones DA, Maganaris CN. The effects of agonist and antagonist muscle activation on the knee extension moment-angle relationship in adults and children. Eur J Appl Physiol. 2009 Aug;106(6):849-56. doi: 10.1007/s00421-009-1088-4. Epub 2009 May 27.
PubMed 19471955
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ForceLoss: Part II - Osteoarthritic Patients. Development and Validation of Methods to Generate Personalised Models for the Differential Diagnosis of the Loss of Muscle Force
- ClinicalTrials.gov ID
- NCT05795348
- Acronym / sponsor ID
- ForceLoss II / ForceLoss II
- Conditions
- Osteoarthritis, Knee
- Keywords
- Dynapenia, Osteoarthritic patients, In Silico Medicine, Digital Twins, Maximal Voluntary Isometric Contraction, Musculoskeletal Modeling, Dynamometry, Electromyography
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Istituto Ortopedico RizzoliUniversity, hospital or other
- Study start
- 28 Mar 2023 (actual)
- Primary completion
- 27 May 2024 (actual)
- Study completion
- 27 May 2024 (actual)
- First posted
- 3 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Knee Osteoarthritic Patients | Other | Diagnostic Test: Personalised Musculoskeletal ModelingPatients 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. |
Who may qualify
- Ages
- 65 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- Neurological, rheumatic or tumoral diseases
- Inguinal or abdominal hernia
- Diabetes
- Severe Hypertension (Level 3)
- Severe Cardio-pulmonary insufficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Personalised Musculoskeletal ModelingAlso: Clinical measures (BIA, Hand-grip test), Clinical questionnaires (WOMAC, KSS)Magnetic resonance images, electromyography and dynamometry data will be used to develop and inform personalised musculoskeletal models | Diagnostic test | Knee Osteoarthritic Patients |
Primary outcome
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.
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.
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.
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2024.
- Background: PubMed 27051510Fernandez J, Zhang J, Heidlauf T, Sartori M, Besier T, Rohrle O, Lloyd D. Multiscale musculoskeletal modelling, data-model fusion and electromyography-informed modelling. Interface Focus. 2016 Apr 6;6(2):20150084. doi: 10.1098/rsfs.2015.0084.
- Background: PubMed 11018445Hermens HJ, Freriks B, Disselhorst-Klug C, Rau G. Development of recommendations for SEMG sensors and sensor placement procedures. J Electromyogr Kinesiol. 2000 Oct;10(5):361-74. doi: 10.1016/s1050-6411(00)00027-4.
- Background: PubMed 18379202Petterson SC, Barrance P, Buchanan T, Binder-Macleod S, Snyder-Mackler L. Mechanisms underlying quadriceps weakness in knee osteoarthritis. Med Sci Sports Exerc. 2008 Mar;40(3):422-7. doi: 10.1249/MSS.0b013e31815ef285.
- Background: PubMed 19954822Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms and treatment perspectives. Semin Arthritis Rheum. 2010 Dec;40(3):250-66. doi: 10.1016/j.semarthrit.2009.10.001. Epub 2009 Dec 2.
- Background: PubMed 30496308Pons C, Borotikar B, Garetier M, Burdin V, Ben Salem D, Lempereur M, Brochard S. Quantifying skeletal muscle volume and shape in humans using MRI: A systematic review of validity and reliability. PLoS One. 2018 Nov 29;13(11):e0207847. doi: 10.1371/journal.pone.0207847. eCollection 2018.
- Background: PubMed 21444359Manini TM, Clark BC. Dynapenia and aging: an update. J Gerontol A Biol Sci Med Sci. 2012 Jan;67(1):28-40. doi: 10.1093/gerona/glr010. Epub 2011 Mar 28.
- Background: PubMed 19471955O'Brien TD, Reeves ND, Baltzopoulos V, Jones DA, Maganaris CN. The effects of agonist and antagonist muscle activation on the knee extension moment-angle relationship in adults and children. Eur J Appl Physiol. 2009 Aug;106(6):849-56. doi: 10.1007/s00421-009-1088-4. Epub 2009 May 27.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Viceconti, Professor principal investigator
IRCCS Istituto Ortopedico Rizzoli
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Personalised Musculoskeletal Modeling in people with Osteoarthritis, Knee, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle volume (time frame: at baseline (Day 0)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05795348, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2024.