Cartilage DestructionNCT05454605
Оptical Spectroscopy in the Diagnosis of Intra-articular Injuries
An observational study of Cartilage Destruction, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
Trial summary
Intra-articular joint injuries are the most common and prognostically unfavorable in case of untimely or erroneous diagnosis, which leads to a significant violation of the quality of life and activity of patients. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Cartilage Destruction
- How many people
- 48 participants
- Where
- 1 siteRussia
- Study dates
- 24 Jan 2022to 20 Nov 2023
- Phase
- Observational
- 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 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Work will be carried out with biological samples of bone and cartilage tissue in compliance with all ethical standards: work with explants (38 samples), as well as in vivo measurements - intraoperatively (10 patients).
Who may be able to join
- Written informed consent of the patient to participate in the study.
- The age of the patient is from 18 to 85 years.
- Gender male and female.
- The patient has intra-articular injuries of the knee joint.
Who cannot join
- Refusal to participate in the study and to sign informed consent.
- The age of the patient is less than 18 and more than 85 years.
- Pregnancy, lactation.
- The presence of severe concomitant somatic pathology (diseases of the cardiovascular system, lungs, liver and kidneys), decompensated diabetes mellitus.
- Oncological diseases.
- Mental illness.
- Alcohol abuse or drug use.
- Chronic viral and bacterial infections in the acute stage.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Оptical Spectroscopy in the Diagnosis of Intra-articular Injuries of the Knee Joint
Intra-articular joint injuries are the most common and prognostically unfavorable in case of untimely or erroneous diagnosis, which leads to a significant violation of the quality of life and activity of patients. For example, untimely diagnosis and determination of the degree of damage to the subchondral bone can lead to progression, namely, an increase in the edema zone with transformation into an irreversible process - avascular necrosis of the bone. Mistakes in diagnosing subsynovial injuries of the ligamentous apparatus and assessing its functional viability can lead to the development of chronic joint instability, chronic synovitis, and progression of intraarticular destruction.
Methods of early and accurate diagnosis allow timely and personalized treatment, they are aimed at preventing the development of complications and the need for repeated expensive and often disabling operations. The issue of developing the method of intraoperative navigation with the use of quantitative assessment methods in operations on the musculoskeletal system is also relevant.
Read more
In this regard, the methods of optical spectroscopy and optoacoustics proposed in the project, which can solve the above problems, are of particular relevance.
Thus, the scientific problem to be solved by the proposed project is the development of optical and optoacoustic spectroscopy methods for biomedical diagnostics. The development of new methods and tools capable of detecting and characterizing both early and hidden predictors of the possible progression of osteoarthritis will prevent or reduce the risks of possible complications and irreversible intra-articular changes.
Read the detailed description
The objectives of this work is to create new optical methods for in vivo analysis of the state of cartilage tissue.
Methods: A prospective study will develop an instrument that implements two optical methods for assessing the condition of cartilage tissue: diffuse reflectance spectroscopy (DRS) and near-infrared fluorescence spectroscopy. Explants (knee joint) will be used as experimental material. To assess the diagnostic capabilities of optical spectroscopy methods, studies of the mechanical characteristics of cartilage will be carried out simultaneously with the optical characteristics. Cartilage mechanical parameters will be measured using a Mach-1 v500c indenter (Biomomentum, Laval, QC, Canada) equipped with a three-axis dynamometer. The direction of the normal to the sample will be measured with a spherical indenter; a needle puncture will be performed to assess the thickness of the explant tissue. Measurements will determine the Young's modulus, the direction of the normal and the thickness of the cartilage. This work is supported by the Russian Science Foundation (grant no. 21-79-10325).
An indentation will be performed to determine the mechanical parameters of the cartilage at different points and to obtain DCR spectra of the cartilage in the wavelength range of 850-1050 nm.Analysis of changes in the properties of water in the cartilaginous tissue of the knee joint in normal and pathological conditions will be supplemented by a study of its own IR fluorescence. In preliminary experiments, it was found that different parts of the cartilage of different explants have different levels of red fluorescence at different stages of degeneration, however, in order to draw conclusions, it is necessary to expand the number of measured samples to assess the reliability of the results of the observed differences.
In the course of the work, a mobile unit will be developed that implements the methods of fluorescence spectroscopy in the near infrared range and DLS, and the mechanical properties of explants will also be studied. In the future, it is planned to use the developed technique for assessing the state of the cartilage intraoperatively.
Before conducting the experimental work, it is planned to write a systematic review on the research topic.
- Conditions
- Cartilage Destruction
- Keywords
- cartilage, regeneration, destruction, knee, intraarticular lesions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| group 1, ex vivo | 1. Assessment of the degree of cartilage damage according to the International Cartilage Regeneration \& Joint Preservation Society (ICRS) classification. 2. Optical spectroscopy of patient tissue samples. 3. Study of the mechanical properties of intra-articular tissues and cartilage thickness with an indenter. 4. Histological assessment of tissues according to the Osteoarthritis Research Society International (OARSI) classification. | |
| group 2, in vivo | 1. Assessment of the degree of cartilage damage according to the ICRS classification. 2. Optical spectroscopy during arthroscopy/arthroplasty. 3. Magnetic resonance imaging (MRI). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of mechanical properties and application of cartilage by indentation method
Micromechanical system Mach-1™ v500csst (Biomomentum Inc., Laval, Quebec, Canada) allows to perform normal alignment and indentation mapping by simultaneously moving the three stages with the use of multiple-axis load cell. After mapping in the normal indentation mode, the cartilage thickness was measured at the same points in the mapping mode by needle penetration technique.
The Lee-Radock model corrected for the finite local thickness of the soft layer was used to estimate the mechanical parameters. The experimental curves were processed by the standard Hertz's model. Numerical processing was performed in MATLAB (MathWorks, USA) using previously developed algorithms.
A standard linear solid (SLS) model was chosen as a relaxation function to describe experiments on indentation-relaxation tests of cartilage tissue, where the main parameters are: instantaneous Young modulus E0, equilibrium Young modulus E, and relaxation time.
Measured: The processing of the received data will be carried out from March 2022 to December 2023.
Reflectance and Cartilage Water Measurement by Diffuse Reflectance Spectroscopy (DRS)
DRS measurements were performed in the spectral region of 850-1050 nm. The tungsten-halogen lamp (Thorlabs, Germany) was used as a light source. The measurements were performed with two 550 μm fibers with a 2.5 mm distance between the centers of their faces, the first one guiding the light to the sample and the second one attached to the QE65000 spectrometer (OceanOptics, USA). For spectra measurement, a specially probe was used, which makes it possible to use it in conjunction with the micromechanical tester setup.
Before each series of experiments, the reference spectrum (reflection from the reference diffuse reflectance) and the background spectrum are measured, and the reflectance and effective optical density are calculated.
Measured: The processing of the received data will be carried out from March 2022 to December 2023.
Simulation of light propagation in the explant by the Monte Carlo method.
In order to estimate the dependencies of the observed parameters on the properties of tissue such as cartilage thickness, water content and scattering properties, light propagation in the explant was simulated using the Monte Carlo method. The explant was modeled as a medium consisting of 2 distinct layers with individual scattering and absorption properties. The first layer represented cartilage, where the main absorption is determined by the OH line of water at ~980 nm, the second layer represented bone tissue, whose absorption possesses a local maximum at ~930 nm, determined by the CH line of the bone matrix.
Measured: The processing of the received data will be carried out from March 2022 to December 2023.
Assessment of the comparison of osteoarthritis grades according to ICRS using the nonparametric Mann-Whitney U-test
Multiple-group statistical comparisons among different ICRS osteoarthritic grades were assessed by nonparametric Mann-Whitney U test using custom-made scripts based on the Python programming language with statsmodels, SciPy libraries. In total, 600 DRS spectra obtained for each ICRS grade (i.e., group) of OA cartilage were used for this test. The assumptions (i.e., independent measurements, non-normal distribution, and similar var-iability) of Mann-Whitney U test were verified. The p-values for each pairwise Mann-Whitney U test were then recalculated using the Bonferroni correction. In all multiple-group pairwise comparisons, p-value of less than 0.05 was considered indicative of statistical significance.
Measured: The processing of the received data will be carried out from March 2022 to December 2023.
Histological examination of bone and cartilage samples
For histological examination, samples were fixed in a 10% neutral formalin (HistoSafe, Biovitrum), were decalcified in a special solution (SoftyDek, Biovitrum) during 24 hours, washed in running water for an hour, subjected to standard alcohol wiring and poured with paraffin. 4-μm-thick paraffin sections were stained with Safranin O and fast green according to the standard protocol. The obtained microscopic preparations were studied using a universal microscope LEICA DM4000 B LED (Leica Microsystems, Germany) equipped with a digital video camera LEICA DFC7000 T (Leica Microsystems, Germany). To verify the degree of cartilage degradation, a histological study will carried out on a selection of explants.
Measured: The processing of the received data will be carried out from March 2022 to December 2023.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2022
- Study start24 Jan 2022
- Primary completion20 Oct 2023
- Study completion20 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cartilage DestructionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Ecologic or community
- Time perspective
- Prospective
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- I.M. Sechenov First Moscow State Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexey Lychagin, Study chair, IM Sechenov UniversityYuliya Goncharuk, Principal investigator, IM Sechenov University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05454605
- Sponsor's protocol ID
- 01-22
- Status last verified
- May 2023
- First submitted
- 12 May 2022
- Last updated
- 18 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Оptical Spectroscopy in the Diagnosis of Intra-articular Injuries of the Knee Joint
- ClinicalTrials.gov ID
- NCT05454605
- Acronym / sponsor ID
- 01-22
- Conditions
- Cartilage Destruction
- Keywords
- cartilage, regeneration, destruction, knee, intraarticular lesions
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- I.M. Sechenov First Moscow State Medical UniversityUniversity, hospital or other
- Study start
- 24 Jan 2022 (actual)
- Primary completion
- 20 Oct 2023 (actual)
- Study completion
- 20 Nov 2023 (actual)
- First posted
- 12 Jul 2022 (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.
Intra-articular joint injuries are the most common and prognostically unfavorable in case of untimely or erroneous diagnosis, which leads to a significant violation of the quality of life and activity of patients. For example, untimely diagnosis and determination of the degree of damage to the subchondral bone can lead to progression, namely, an increase in the edema zone with transformation into an irreversible process - avascular necrosis of the bone. Mistakes in diagnosing subsynovial injuries of the ligamentous apparatus and assessing its functional viability can lead to the development of chronic joint instability, chronic synovitis, and progression of intraarticular destruction.
Methods of early and accurate diagnosis allow timely and personalized treatment, they are aimed at preventing the development of complications and the need for repeated expensive and often disabling operations. The issue of developing the method of intraoperative navigation with the use of quantitative assessment methods in operations on the musculoskeletal system is also relevant.
In this regard, the methods of optical spectroscopy and optoacoustics proposed in the project, which can solve the above problems, are of particular relevance.
Thus, the scientific problem to be solved by the proposed project is the development of optical and optoacoustic spectroscopy methods for biomedical diagnostics. The development of new methods and tools capable of detecting and characterizing both early and hidden predictors of the possible progression of osteoarthritis will prevent or reduce the risks of possible complications and irreversible intra-articular changes.
Detailed description
The objectives of this work is to create new optical methods for in vivo analysis of the state of cartilage tissue.
Methods: A prospective study will develop an instrument that implements two optical methods for assessing the condition of cartilage tissue: diffuse reflectance spectroscopy (DRS) and near-infrared fluorescence spectroscopy. Explants (knee joint) will be used as experimental material. To assess the diagnostic capabilities of optical spectroscopy methods, studies of the mechanical characteristics of cartilage will be carried out simultaneously with the optical characteristics. Cartilage mechanical parameters will be measured using a Mach-1 v500c indenter (Biomomentum, Laval, QC, Canada) equipped with a three-axis dynamometer. The direction of the normal to the sample will be measured with a spherical indenter; a needle puncture will be performed to assess the thickness of the explant tissue. Measurements will determine the Young's modulus, the direction of the normal and the thickness of the cartilage. This work is supported by the Russian Science Foundation (grant no. 21-79-10325).
An indentation will be performed to determine the mechanical parameters of the cartilage at different points and to obtain DCR spectra of the cartilage in the wavelength range of 850-1050 nm.Analysis of changes in the properties of water in the cartilaginous tissue of the knee joint in normal and pathological conditions will be supplemented by a study of its own IR fluorescence. In preliminary experiments, it was found that different parts of the cartilage of different explants have different levels of red fluorescence at different stages of degeneration, however, in order to draw conclusions, it is necessary to expand the number of measured samples to assess the reliability of the results of the observed differences.
In the course of the work, a mobile unit will be developed that implements the methods of fluorescence spectroscopy in the near infrared range and DLS, and the mechanical properties of explants will also be studied. In the future, it is planned to use the developed technique for assessing the state of the cartilage intraoperatively.
Before conducting the experimental work, it is planned to write a systematic review on the research topic.
Study design
- Observational model
- Ecologic or community
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| group 1, ex vivo | – | –1. Assessment of the degree of cartilage damage according to the International Cartilage Regeneration \& Joint Preservation Society (ICRS) classification. 2. Optical spectroscopy of patient tissue samples. 3. Study of the mechanical properties of intra-articular tissues and cartilage thickness with an indenter. 4. Histological assessment of tissues according to the Osteoarthritis Research Society International (OARSI) classification. |
| group 2, in vivo | – | –1. Assessment of the degree of cartilage damage according to the ICRS classification. 2. Optical spectroscopy during arthroscopy/arthroplasty. 3. Magnetic resonance imaging (MRI). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Work will be carried out with biological samples of bone and cartilage tissue in compliance with all ethical standards: work with explants (38 samples), as well as in vivo measurements - intraoperatively (10 patients).
Key inclusion criteria (4 listed)
- Written informed consent of the patient to participate in the study.
- The age of the patient is from 18 to 85 years.
- Gender male and female.
- The patient has intra-articular injuries of the knee joint.
Key exclusion criteria (8 listed)
- Refusal to participate in the study and to sign informed consent.
- The age of the patient is less than 18 and more than 85 years.
- Pregnancy, lactation.
- The presence of severe concomitant somatic pathology (diseases of the cardiovascular system, lungs, liver and kidneys), decompensated diabetes mellitus.
- Oncological diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Measurement of mechanical properties and application of cartilage by indentation method
Time frame: The processing of the received data will be carried out from March 2022 to December 2023.
Micromechanical system Mach-1™ v500csst (Biomomentum Inc., Laval, Quebec, Canada) allows to perform normal alignment and indentation mapping by simultaneously moving the three stages with the use of multiple-axis load cell. After mapping in the normal indentation mode, the cartilage thickness was measured at the same points in the mapping mode by needle penetration technique. The Lee-Radock model corrected for the finite local thickness of the soft layer was used to estimate the mechanical parameters. The experimental curves were processed by the standard Hertz's model. Numerical processing was performed in MATLAB (MathWorks, USA) using previously developed algorithms. A standard linear solid (SLS) model was chosen as a relaxation function to describe experiments on indentation-relaxation tests of cartilage tissue, where the main parameters are: instantaneous Young modulus E0, equilibrium Young modulus E, and relaxation time.
Reflectance and Cartilage Water Measurement by Diffuse Reflectance Spectroscopy (DRS)
Time frame: The processing of the received data will be carried out from March 2022 to December 2023.
DRS measurements were performed in the spectral region of 850-1050 nm. The tungsten-halogen lamp (Thorlabs, Germany) was used as a light source. The measurements were performed with two 550 μm fibers with a 2.5 mm distance between the centers of their faces, the first one guiding the light to the sample and the second one attached to the QE65000 spectrometer (OceanOptics, USA). For spectra measurement, a specially probe was used, which makes it possible to use it in conjunction with the micromechanical tester setup. Before each series of experiments, the reference spectrum (reflection from the reference diffuse reflectance) and the background spectrum are measured, and the reflectance and effective optical density are calculated.
Simulation of light propagation in the explant by the Monte Carlo method.
Time frame: The processing of the received data will be carried out from March 2022 to December 2023.
In order to estimate the dependencies of the observed parameters on the properties of tissue such as cartilage thickness, water content and scattering properties, light propagation in the explant was simulated using the Monte Carlo method. The explant was modeled as a medium consisting of 2 distinct layers with individual scattering and absorption properties. The first layer represented cartilage, where the main absorption is determined by the OH line of water at ~980 nm, the second layer represented bone tissue, whose absorption possesses a local maximum at ~930 nm, determined by the CH line of the bone matrix.
Assessment of the comparison of osteoarthritis grades according to ICRS using the nonparametric Mann-Whitney U-test
Time frame: The processing of the received data will be carried out from March 2022 to December 2023.
Multiple-group statistical comparisons among different ICRS osteoarthritic grades were assessed by nonparametric Mann-Whitney U test using custom-made scripts based on the Python programming language with statsmodels, SciPy libraries. In total, 600 DRS spectra obtained for each ICRS grade (i.e., group) of OA cartilage were used for this test. The assumptions (i.e., independent measurements, non-normal distribution, and similar var-iability) of Mann-Whitney U test were verified. The p-values for each pairwise Mann-Whitney U test were then recalculated using the Bonferroni correction. In all multiple-group pairwise comparisons, p-value of less than 0.05 was considered indicative of statistical significance.
Histological examination of bone and cartilage samples
Time frame: The processing of the received data will be carried out from March 2022 to December 2023.
For histological examination, samples were fixed in a 10% neutral formalin (HistoSafe, Biovitrum), were decalcified in a special solution (SoftyDek, Biovitrum) during 24 hours, washed in running water for an hour, subjected to standard alcohol wiring and poured with paraffin. 4-μm-thick paraffin sections were stained with Safranin O and fast green according to the standard protocol. The obtained microscopic preparations were studied using a universal microscope LEICA DM4000 B LED (Leica Microsystems, Germany) equipped with a digital video camera LEICA DFC7000 T (Leica Microsystems, Germany). To verify the degree of cartilage degradation, a histological study will carried out on a selection of explants.
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 18 Jan 2024.
- Individual participant dataSharing planned: No
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.
Alexey Lychagin study chair
IM Sechenov University
Yuliya Goncharuk principal investigator
IM Sechenov University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cartilage Destruction, run by I.M. Sechenov First Moscow State Medical University at 1 site in Russia.
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 18 Jan 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 Russia. 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?
Measurement of mechanical properties and application of cartilage by indentation method (time frame: The processing of the received data will be carried out from March 2022 to December 2023.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jan 2024.