Knee OsteoarthritisKNEELOXNCT07875296
Lysyl Oxidase and Lysyl Hydroxylase Levels in Knee Osteoarthritis
An observational study of Knee Osteoarthritis, run by Afyonkarahisar Health Sciences University at 1 site in Turkey (Türkiye).
Trial summary
The aim of this study is to investigate the serum levels of lysyl hydroxylase, lysyl oxidase, and the lysyl oxidase-like enzymes in patients with different stages of knee osteoarthritis and to compare these findings with those of healthy control subjects. Read more about this study
- Who is it for?
- Ages 40 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Knee Osteoarthritis
- How many people
- 200 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 5 May 2025to 3 Apr 2027
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 40 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study population will consist of female volunteers aged 40-70 years who are either diagnosed with knee osteoarthritis or are healthy controls without clinical or radiographic evidence of osteoarthritis. Participants will be recruited from the outpatient clinic of the Department of Physical Medicine and Rehabilitation, Afyonkarahisar Health Sciences University (AFSU). All participants will meet the inclusion criteria and provide written informed consent prior to enrollment. Individuals with metabolic diseases, inflammatory arthritis, or significant comorbidities will be excluded.
Who may be able to join
- Female participants aged between 40 and 70 years.
- Diagnosed with knee osteoarthritis according to clinical and radiographic criteria, and presenting to the Department of Physical Medicine and Rehabilitation, Afyonkarahisar Health Sciences University (AFSU).
- Body Mass Index (BMI) between 18.5 and 40 kg/m².
Who cannot join
- Presence of metabolic diseases or severe comorbidities, including uncontrolled diabetes mellitus, chronic kidney disease (GFR < 60 mL/min/1.73 m²), liver failure, malignancy, severe cardiovascular disease, chronic respiratory disorders, or chronic intestinal diseases.
- Any inflammatory arthritis or other rheumatologic disease with related signs or symptoms.
- History of knee trauma involving cruciate ligaments or menisci within the past 3 months.
- Secondary osteoarthritis due to other joint disorders such as septic arthritis, avascular necrosis, or Paget's disease.
- History of previous knee surgery.
- Recent intra-articular injection to the knee joint within the last 3 months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Afyonkarahisar Health Sciences University, Department of Physical Medicine and Rehabilitation
Afyonkarahisar, 03030
About this study
Official title: Lysyl Oxidase and Lysyl Hydroxylase Levels in Patients With Knee Osteoarthritis
The aim of this study is to investigate the serum levels of lysyl hydroxylase, lysyl oxidase, and the lysyl oxidase-like enzymes in patients with different stages of knee osteoarthritis and to compare these findings with those of healthy control subjects.
Read the detailed description
Osteoarthritis (OA) is a chronic degenerative disease affecting synovial joints, characterized by structural abnormalities of the hyaline articular cartilage, subchondral bone loss, increased synovial vascularity, tissue hypertrophy, and ligament or tendon instability. These changes lead to pain, swelling, and reduced range of motion. The pathogenesis of OA involves inflammation, genetic predisposition, mechanical stress, biochemical alterations, and environmental factors, all of which disrupt the balance between cartilage synthesis and degradation.
The extracellular matrix (ECM) of articular cartilage is composed mainly of collagen, proteoglycans, and non-collagenous proteins, providing biomechanical strength and resilience. Collagen cross-linking, which stabilizes the ECM, depends on post-translational modifications regulated by specific enzymes such as lysyl hydroxylase and lysyl oxidase.
Lysyl hydroxylases catalyze the hydroxylation of lysine residues to hydroxylysine, a key step in collagen cross-link formation. Lysyl oxidase (LOX) and its related isoenzymes (LOXL1-4) are copper-dependent amine oxidases that mediate oxidative deamination of lysine and hydroxylysine residues, forming aldehydes that initiate covalent cross-links between collagen and elastin molecules. Proper LOX activity is crucial for maintaining the mechanical integrity of cartilage, while dysregulation of LOX family enzymes may contribute to matrix fragility and degeneration.
The expression and activity of LOX family enzymes in OA cartilage appear to vary by disease stage. LOXL2 and LOXL3 have been implicated in both anabolic and catabolic responses, suggesting complex regulatory roles. Understanding these enzyme dynamics may provide insights into the pathophysiology of OA and identify potential biomarkers or therapeutic targets.
The present study aims to evaluate serum levels of lysyl hydroxylase, lysyl oxidase, and LOXL1-4 in patients with different stages of knee osteoarthritis and compare them with healthy control subjects.
- Conditions
- Knee Osteoarthritis
- Keywords
- Enzyme, Biomarkers, Knee Osteoarthritis, Lysyl Hydroxylase, LOX, LOXL
- Medical subject headings
- Osteoarthritis, Knee
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 |
|---|---|---|
| KL 1 OA | Radiographically confirmed knee OA, Kellgren-Lawrence grade 1 | |
| KL 2 OA | Radiographically confirmed knee OA, Kellgren-Lawrence grade 2 | |
| KL 3 OA | Radiographically confirmed knee OA, Kellgren-Lawrence grade 3 | |
| KL 4 OA | Radiographically confirmed knee OA, Kellgren-Lawrence grade 4 | |
| Controls | Age- and sex-matched individuals without clinical or radiographic knee OA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biochemical Analysis
Serum levels of lysyl oxidase (LOX), lysyl oxidase-like enzymes (LOXL1, LOXL2, LOXL3, LOXL4), and lysyl hydroxylase (LH) will be quantified using validated, commercially available sandwich-type ELISA kits. Venous blood samples will be obtained from fasting participants, centrifuged to separate serum, aliquoted, and stored at -80 °C under single freeze-thaw conditions until analysis. Each ELISA plate will include standard curves and control samples. Optical density will be read at 450 nm, and results will be expressed as ng/mL or pg/mL according to manufacturer instructions. Intra-assay coefficients of variation (CV) exceeding 15% will be repeated to ensure analytical accuracy. All samples will be anonymized and analyzed under strict confidentiality.
Measured: At the time of enrollment
Secondary outcomes (4)
Femoral Cartilage Thickness (Ultrasound Measurement)
Ultrasonographic evaluation will be performed using a linear transducer (4-15 MHz, MyLab X8 series, Esaote S.p.A., Italy). Participants will be examined in the supine position with knees flexed at 120-135°, and the probe will be placed axially over the suprapatellar region. The distal femoral cartilage will be visualized as an anechoic band between the sharp hyperechoic cortical line and the suprapatellar fat pad. Three measurements will be taken from each knee at standard reference points: right lateral condyle (RLC), intercondylar area (RIA), and right medial condyle (RMC). All images will be reviewed by a physician with over three years of musculoskeletal ultrasound experience, and images with poor quality or incorrect technique will be excluded from the analysis.
Measured: At the time of enrollment
Knee Joint Range of Motion (ROM)
Active and passive range of motion (flexion and extension) of the affected knee joint will be measured using a universal goniometer in a standardized sitting or supine position. Measurements will be performed by the same examiner to ensure consistency, and results will be recorded in degrees (°). The purpose is to assess the relationship between joint mobility and disease severity.
Measured: At the time of enrollment
Pain Intensity (VAS Score)
Pain intensity will be assessed using a 10-cm Visual Analog Scale (VAS), where 0 indicates "no pain" and 10 indicates "worst imaginable pain." Participants will be asked to rate their average knee pain during daily activities. The mean VAS score will be compared across osteoarthritis stages and correlated with biochemical and ultrasound findings.
Measured: At the time of enrollment
Functional Status (WOMAC Index - Likert Scale)
Functional impairment will be evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), scored on a 5-point Likert scale (0 = none, 4 = extreme). The WOMAC index assesses pain, stiffness, and physical function through 24 questions (5 on pain, 2 on stiffness, and 17 on physical function). Total and subscale scores will be calculated to quantify the impact of knee osteoarthritis on daily living activities and functional capacity. The total WOMAC score ranges from 0 to 96. Higher scores indicate greater pain, stiffness and functional impairment, reflecting worse clinical outcomes.
Measured: At the time of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2026
- Study start5 May 2025
- Primary completion3 Jan 2027 (estimated)
- Study completion3 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 200 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Afyonkarahisar Health Sciences University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hasan Toktaş, Afyonkarahisar Health Sciences University
- Investigators
- Hasan Toktaş, Professor, Principal investigator, Afyonkarahisar Health Sciences University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07875296
- Sponsor's protocol ID
- AFSU-EIK-567
- Acronym
- KNEELOX
- Status last verified
- Oct 2026
- First submitted
- 5 Oct 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Morici L, Allemann E, Jordan O, Nikolic I. Promising LOX proteins for cartilage-targeting osteoarthritis therapy. Pharmacol Res. 2025 Feb;212:107627. doi: 10.1016/j.phrs.2025.107627. Epub 2025 Jan 26.
PubMed 39875019Raut RD, Choudhury C, Ali F, Chakraborty AK, Ahmed MM, Del Valle-Ponce De Leon C, Modh HV, Mehra P, Fan Y, Almarza A, Bais MV. LOXL2 Deletion Triggers TMJ Osteoarthritis While Overexpression Protects Against NF-kappabeta-Induced Chondrocyte Apoptosis. bioRxiv [Preprint]. 2025 May 13:2025.05.12.653519. doi: 10.1101/2025.05.12.653519.
PubMed 40463059Wei Q. Apoptosis Activation and Autophagy Inhibition of Chondrocytes by Leptin by the Upregulation of LOXL3 in Osteoarthritis Pathogenesis. J Healthc Eng. 2022 Jan 7;2022:4026128. doi: 10.1155/2022/4026128. eCollection 2022.
PubMed 35035830
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lysyl Oxidase and Lysyl Hydroxylase Levels in Patients With Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT07875296
- Acronym / sponsor ID
- KNEELOX / AFSU-EIK-567
- Conditions
- Knee Osteoarthritis
- Keywords
- Enzyme, Biomarkers, Knee Osteoarthritis, Lysyl Hydroxylase, LOX, LOXL
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Afyonkarahisar Health Sciences UniversityUniversity, hospital or other
- Study start
- 5 May 2025 (actual)
- Primary completion
- 3 Jan 2027 (estimated)
- Study completion
- 3 Apr 2027 (estimated)
- First posted
- 15 Oct 2026 (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 aim of this study is to investigate the serum levels of lysyl hydroxylase, lysyl oxidase, and the lysyl oxidase-like enzymes in patients with different stages of knee osteoarthritis and to compare these findings with those of healthy control subjects.
Detailed description
Osteoarthritis (OA) is a chronic degenerative disease affecting synovial joints, characterized by structural abnormalities of the hyaline articular cartilage, subchondral bone loss, increased synovial vascularity, tissue hypertrophy, and ligament or tendon instability. These changes lead to pain, swelling, and reduced range of motion. The pathogenesis of OA involves inflammation, genetic predisposition, mechanical stress, biochemical alterations, and environmental factors, all of which disrupt the balance between cartilage synthesis and degradation.
The extracellular matrix (ECM) of articular cartilage is composed mainly of collagen, proteoglycans, and non-collagenous proteins, providing biomechanical strength and resilience. Collagen cross-linking, which stabilizes the ECM, depends on post-translational modifications regulated by specific enzymes such as lysyl hydroxylase and lysyl oxidase.
Lysyl hydroxylases catalyze the hydroxylation of lysine residues to hydroxylysine, a key step in collagen cross-link formation. Lysyl oxidase (LOX) and its related isoenzymes (LOXL1-4) are copper-dependent amine oxidases that mediate oxidative deamination of lysine and hydroxylysine residues, forming aldehydes that initiate covalent cross-links between collagen and elastin molecules. Proper LOX activity is crucial for maintaining the mechanical integrity of cartilage, while dysregulation of LOX family enzymes may contribute to matrix fragility and degeneration.
The expression and activity of LOX family enzymes in OA cartilage appear to vary by disease stage. LOXL2 and LOXL3 have been implicated in both anabolic and catabolic responses, suggesting complex regulatory roles. Understanding these enzyme dynamics may provide insights into the pathophysiology of OA and identify potential biomarkers or therapeutic targets.
The present study aims to evaluate serum levels of lysyl hydroxylase, lysyl oxidase, and LOXL1-4 in patients with different stages of knee osteoarthritis and compare them with healthy control subjects.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| KL 1 OA | – | –Radiographically confirmed knee OA, Kellgren-Lawrence grade 1 |
| KL 2 OA | – | –Radiographically confirmed knee OA, Kellgren-Lawrence grade 2 |
| KL 3 OA | – | –Radiographically confirmed knee OA, Kellgren-Lawrence grade 3 |
| KL 4 OA | – | –Radiographically confirmed knee OA, Kellgren-Lawrence grade 4 |
| Controls | – | –Age- and sex-matched individuals without clinical or radiographic knee OA |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will consist of female volunteers aged 40-70 years who are either diagnosed with knee osteoarthritis or are healthy controls without clinical or radiographic evidence of osteoarthritis. Participants will be recruited from the outpatient clinic of the Department of Physical Medicine and Rehabilitation, Afyonkarahisar Health Sciences University (AFSU). All participants will meet the inclusion criteria and provide written informed consent prior to enrollment. Individuals with metabolic diseases, inflammatory arthritis, or significant comorbidities will be excluded.
Key inclusion criteria (3 listed)
- Female participants aged between 40 and 70 years.
- Diagnosed with knee osteoarthritis according to clinical and radiographic criteria, and presenting to the Department of Physical Medicine and Rehabilitation, Afyonkarahisar Health Sciences University (AFSU).
- Body Mass Index (BMI) between 18.5 and 40 kg/m².
Key exclusion criteria (6 listed)
- Presence of metabolic diseases or severe comorbidities, including uncontrolled diabetes mellitus, chronic kidney disease (GFR < 60 mL/min/1.73 m²), liver failure, malignancy, severe cardiovascular disease, chronic respiratory disorders, or chronic intestinal diseases.
- Any inflammatory arthritis or other rheumatologic disease with related signs or symptoms.
- History of knee trauma involving cruciate ligaments or menisci within the past 3 months.
- Secondary osteoarthritis due to other joint disorders such as septic arthritis, avascular necrosis, or Paget's disease.
- History of previous knee surgery.
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
Biochemical Analysis
Time frame: At the time of enrollment
Serum levels of lysyl oxidase (LOX), lysyl oxidase-like enzymes (LOXL1, LOXL2, LOXL3, LOXL4), and lysyl hydroxylase (LH) will be quantified using validated, commercially available sandwich-type ELISA kits. Venous blood samples will be obtained from fasting participants, centrifuged to separate serum, aliquoted, and stored at -80 °C under single freeze-thaw conditions until analysis. Each ELISA plate will include standard curves and control samples. Optical density will be read at 450 nm, and results will be expressed as ng/mL or pg/mL according to manufacturer instructions. Intra-assay coefficients of variation (CV) exceeding 15% will be repeated to ensure analytical accuracy. All samples will be anonymized and analyzed under strict confidentiality.
4 secondary outcomes
Femoral Cartilage Thickness (Ultrasound Measurement)
Time frame: At the time of enrollment
Knee Joint Range of Motion (ROM)
Time frame: At the time of enrollment
Pain Intensity (VAS Score)
Time frame: At the time of enrollment
Functional Status (WOMAC Index - Likert Scale)
Time frame: At the time of enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Background: PubMed 39875019Morici L, Allemann E, Jordan O, Nikolic I. Promising LOX proteins for cartilage-targeting osteoarthritis therapy. Pharmacol Res. 2025 Feb;212:107627. doi: 10.1016/j.phrs.2025.107627. Epub 2025 Jan 26.
- Background: PubMed 40463059Raut RD, Choudhury C, Ali F, Chakraborty AK, Ahmed MM, Del Valle-Ponce De Leon C, Modh HV, Mehra P, Fan Y, Almarza A, Bais MV. LOXL2 Deletion Triggers TMJ Osteoarthritis While Overexpression Protects Against NF-kappabeta-Induced Chondrocyte Apoptosis. bioRxiv [Preprint]. 2025 May 13:2025.05.12.653519. doi: 10.1101/2025.05.12.653519.
- Background: PubMed 35035830Wei Q. Apoptosis Activation and Autophagy Inhibition of Chondrocytes by Leptin by the Upregulation of LOXL3 in Osteoarthritis Pathogenesis. J Healthc Eng. 2022 Jan 7;2022:4026128. doi: 10.1155/2022/4026128. eCollection 2022.
- Promising study exploring LOX proteins as potential targets for cartilage-protective therapy in osteoarthritis.Link provided by the sponsor.
- Experimental research investigating the role of LOXL2 in chondrocyte apoptosis and osteoarthritis progression.Link provided by the sponsor.
- Study analizing leptin-mediated regulation of LOXL3 and its impact on chondrocyte apoptosis and autophagy in osteoarthritisLink provided by the sponsor.
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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.
Hasan Toktaş, Professor principal investigator
Afyonkarahisar Health Sciences 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 Knee Osteoarthritis, run by Afyonkarahisar Health Sciences University at 1 site in Turkey (Türkiye).
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 3 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 15 Oct 2026. 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 Turkey (Türkiye). 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hasan Toktaş, Professor (+905052212901 ext. +905447289558, hasantoktas@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biochemical Analysis (time frame: At the time of enrollment). 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 NCT07875296, which also lists 3 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 15 Oct 2026.