Post-Traumatic Osteoarthritis of KneeCASHNCT05687331
Changes in the Immunomodulatory Properties of Adipose Stromal Cells Due to Hemarthrosis After Knee Injury
An observational study of Post-Traumatic Osteoarthritis of Knee and Knee Injuries, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
The goal of this observational study is to gain insight in the natural course of pro-inflammatory factors and hemarthrosis in patients older than 18 with a recent knee trauma. The main question[s] it aims to answer are: What is the natural course of pro-inflammatory factors and hemarthrosis in knee trauma? What are… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Post-Traumatic Osteoarthritis of Knee, Knee Injuries, Hemarthrosis
- What is being tested?
- knee arthrocentesis, venipuncture and MRI-scan
- Type of treatment
- Surgery or procedure
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 5 Apr 2022to 1 Apr 2024
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adult patients who are presented at the emergency department of the CWZ hospital because of a recent distortion of the knee.
Who may be able to join
- Recently suffered an injury of the index knee (rotational or hyperextension)
- A swollen joint
- Inability to mobilise
Who cannot join
- Patients with an active inflammatory or infectious comorbid disease (including rheumatic diseases)
- Patients using systemic immunosuppressant medication
- Patients with a contra-indication for undergoing a MRI-scan (non-compatible implants or claustrophobia for example)
- Patients with knee prosthesis
- Patients with coagulation disorders
- Patients with a history of a cruciate ligament or meniscal injury of the index knee
- Patients with a tibiofemoral fracture of the index knee due to current distortion
- In case the inclusion of the required amount of patient is reached in one the patient groups, additional patients belonging in the same patient group will not be included in the study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Radboud umc
Nijmegen, Gelderland, 6525GA
Bob Evers, Drs/Msc, 0629630837, Bob.J.Evers@radboudumc.nl
Rogier Thurlings, Dr/PhD, 0629652920, rogier.thurlings@radboudumc.nl
About this study
The goal of this observational study is to gain insight in the natural course of pro-inflammatory factors and hemarthrosis in patients older than 18 with a recent knee trauma. The main question[s] it aims to answer are:
- What is the natural course of pro-inflammatory factors and hemarthrosis in knee trauma?
- What are the effects of inflammation and hemarthrosis on the anti-inflammatory potential of ASC's in order to better determine eligible patients and circumstances for ASC's therapy?
Participants will:
- undergo blood withdrawal
- undergo knee arthrocentesis for synovial fluid sample collection
- physical examination
- fill out a questionnaire on knee complaints
Read the detailed description
Recent studies have found an amelioration of post-traumatic osteoarthritis by the use of adipose-derived stromal cells (ASC's) in an experimental animal model. This amelioration was only seen under inflammatory conditions. The presence of hemarthrosis has not been taken into account in the before mentioned animal model, and might have cytotoxic effects on ASC's and aggravate the inflammatory response. The objective of this study is to gain insight in the natural course of pro-inflammatory factors and hemarthrosis and its effects on the anti-inflammatory potential of ASC's in order to better determine eligible patients and circumstances for ASC's therapy.
Therefore the investigators designed a pilot study with exploratory analyses in and with synovial fluid in a longitudinal cohort.
Our study population will consist of 20 patients, older than 18 years, who sustained a recent knee trauma and are presented to the emergency department.The investigators will gather synovial fluid and blood samples for laboratory analysis perform and physical examination and provide questionnaires for clinical follow-up.
The main study endpoint are the anti-inflammatory capacities of ASC's in synovial fluid that contains blood as a result of hemarthrosis after knee injury.
- Being tested
- knee arthrocentesis, venipuncture, MRI-scan, Physical examination, KOOS questionnaire
- Medical subject headings
- Knee Injuries, Hemarthrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
knee arthrocentesisProcedure or surgery
arthrocentesis of the knee joint to gather a synovial fluid sample
venipunctureProcedure or surgery
Also called blood draw
Peripheral venipuncture to gather a blood sample
MRI-scanDiagnostic test
MRI-scan of the knee
Physical examinationDiagnostic test
Physical examination of the injured knee
KOOS questionnaireOther
KOOS questionnaire of the injured knee
| Study group | Role | What they receive |
|---|---|---|
| Patients with hemarthrosis | 10 patients that sustained a knee trauma and have hemarthrosis during knee arthrocentesis (red color of the synovial fluid) Receives: Procedure: knee arthrocentesis; Procedure: venipuncture; Diagnostic Test: MRI-scan; Diagnostic Test: Physical examination; Other: KOOS questionnaire | |
| Patients without hemarthrosis | 10 patients that sustained a knee trauma and do not have hemarthrosis during knee arthrocentesis (yellow color of the synovial fluid) Receives: Procedure: knee arthrocentesis; Procedure: venipuncture; Diagnostic Test: MRI-scan; Diagnostic Test: Physical examination; Other: KOOS questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
Synovial fluid analysis
Analysis of changes in pro-inflammatory factors, erythrocytes (as measurement for hemarthrosis)
Measured: Samples are taken at week 1, week 2, week 4, week 6 and week 8 after trauma
Secondary outcomes (4)
co-culture of synovial fluid with adipose stromal cells
Assessment of changes in cytotoxity of hemarthrosis in synovial fluid on adipose stromal cells
Measured: samples are taken at week 1, week 2, week 4, week 6 and week 8 after trauma
MRI-imaging
MRI-images to determine post-traumatic changes in the articulate cartilage
Measured: At inclusion and 1 year after trauma
Physical examination
Assessment of changes in swelling, warmth and appearance of the skin
Measured: Physical examination at week 1, week 2, week 4, week 6 and week 8 after trauma
Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire
Assessment changes of knee complaints by using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, with minimum score of 0 and a maximum score of 100 and a higher score meaning a better outcome.
Measured: Questionnaires are taken at week 1, week 2, week 4, week 6 and week 8 after trauma
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2023
- Study start5 Apr 2022
- Primary completion1 Apr 2023 (estimated)
- Study completion1 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Post-Traumatic Osteoarthritis of KneeStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05687331
- Sponsor's protocol ID
- NL77974.091.21
- Acronym
- CASH
- Status last verified
- Dec 2022
- First submitted
- 13 Dec 2022
- Last updated
- 18 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Riordan EA, Little C, Hunter D. Pathogenesis of post-traumatic OA with a view to intervention. Best Pract Res Clin Rheumatol. 2014 Feb;28(1):17-30. doi: 10.1016/j.berh.2014.02.001.
PubMed 24792943Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007 Oct;35(10):1756-69. doi: 10.1177/0363546507307396. Epub 2007 Aug 29.
PubMed 17761605Luc B, Gribble PA, Pietrosimone BG. Osteoarthritis prevalence following anterior cruciate ligament reconstruction: a systematic review and numbers-needed-to-treat analysis. J Athl Train. 2014 Nov-Dec;49(6):806-19. doi: 10.4085/1062-6050-49.3.35.
PubMed 25232663Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis -- results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage. 2005 May;13(5):361-7. doi: 10.1016/j.joca.2005.01.005.
PubMed 15882559Pulles AE, Mastbergen SC, Schutgens RE, Lafeber FP, van Vulpen LF. Pathophysiology of hemophilic arthropathy and potential targets for therapy. Pharmacol Res. 2017 Jan;115:192-199. doi: 10.1016/j.phrs.2016.11.032. Epub 2016 Nov 24.
PubMed 27890816Gupte C, St Mart JP. The acute swollen knee: diagnosis and management. J R Soc Med. 2013 Jul;106(7):259-68. doi: 10.1177/0141076813482831.
PubMed 23821708Wang Y, Shimmin A, Ghosh P, Marks P, Linklater J, Connell D, Hall S, Skerrett D, Itescu S, Cicuttini FM. Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial. Arthritis Res Ther. 2017 Aug 2;19(1):180. doi: 10.1186/s13075-017-1391-0.
PubMed 28768528ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, Jeanson J, Noel D, Casteilla L, Jorgensen C, van den Berg W, van Lent PL. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum. 2012 Nov;64(11):3604-13. doi: 10.1002/art.34626.
PubMed 22961401Schelbergen RF, van Dalen S, ter Huurne M, Roth J, Vogl T, Noel D, Jorgensen C, van den Berg WB, van de Loo FA, Blom AB, van Lent PL. Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8/A9 serum levels. Osteoarthritis Cartilage. 2014 Aug;22(8):1158-66. doi: 10.1016/j.joca.2014.05.022. Epub 2014 Jun 10.
PubMed 24928317Pers YM, Rackwitz L, Ferreira R, Pullig O, Delfour C, Barry F, Sensebe L, Casteilla L, Fleury S, Bourin P, Noel D, Canovas F, Cyteval C, Lisignoli G, Schrauth J, Haddad D, Domergue S, Noeth U, Jorgensen C; ADIPOA Consortium. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Stem Cells Transl Med. 2016 Jul;5(7):847-56. doi: 10.5966/sctm.2015-0245. Epub 2016 May 23.
PubMed 27217345
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in the Immunomodulatory Properties of Adipose Stromal Cells Due to Hemarthrosis After Knee Injury
- ClinicalTrials.gov ID
- NCT05687331
- Acronym / sponsor ID
- CASH / NL77974.091.21
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 5 Apr 2022 (actual)
- Primary completion
- 1 Apr 2023 (estimated)
- Study completion
- 1 Apr 2024 (estimated)
- First posted
- 18 Jan 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 goal of this observational study is to gain insight in the natural course of pro-inflammatory factors and hemarthrosis in patients older than 18 with a recent knee trauma. The main question[s] it aims to answer are:
- What is the natural course of pro-inflammatory factors and hemarthrosis in knee trauma?
- What are the effects of inflammation and hemarthrosis on the anti-inflammatory potential of ASC's in order to better determine eligible patients and circumstances for ASC's therapy?
Participants will:
- undergo blood withdrawal
- undergo knee arthrocentesis for synovial fluid sample collection
- physical examination
- fill out a questionnaire on knee complaints
Detailed description
Recent studies have found an amelioration of post-traumatic osteoarthritis by the use of adipose-derived stromal cells (ASC's) in an experimental animal model. This amelioration was only seen under inflammatory conditions. The presence of hemarthrosis has not been taken into account in the before mentioned animal model, and might have cytotoxic effects on ASC's and aggravate the inflammatory response. The objective of this study is to gain insight in the natural course of pro-inflammatory factors and hemarthrosis and its effects on the anti-inflammatory potential of ASC's in order to better determine eligible patients and circumstances for ASC's therapy.
Therefore the investigators designed a pilot study with exploratory analyses in and with synovial fluid in a longitudinal cohort.
Our study population will consist of 20 patients, older than 18 years, who sustained a recent knee trauma and are presented to the emergency department.The investigators will gather synovial fluid and blood samples for laboratory analysis perform and physical examination and provide questionnaires for clinical follow-up.
The main study endpoint are the anti-inflammatory capacities of ASC's in synovial fluid that contains blood as a result of hemarthrosis after knee injury.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with hemarthrosis | – | Procedure: knee arthrocentesis, Procedure: venipuncture, Diagnostic Test: MRI-scan, Diagnostic Test: Physical examination, Other: KOOS questionnaire10 patients that sustained a knee trauma and have hemarthrosis during knee arthrocentesis (red color of the synovial fluid) |
| Patients without hemarthrosis | – | Procedure: knee arthrocentesis, Procedure: venipuncture, Diagnostic Test: MRI-scan, Diagnostic Test: Physical examination, Other: KOOS questionnaire10 patients that sustained a knee trauma and do not have hemarthrosis during knee arthrocentesis (yellow color of the synovial fluid) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients who are presented at the emergency department of the CWZ hospital because of a recent distortion of the knee.
Key inclusion criteria (3 listed)
- Recently suffered an injury of the index knee (rotational or hyperextension)
- A swollen joint
- Inability to mobilise
Key exclusion criteria (8 listed)
- Patients with an active inflammatory or infectious comorbid disease (including rheumatic diseases)
- Patients using systemic immunosuppressant medication
- Patients with a contra-indication for undergoing a MRI-scan (non-compatible implants or claustrophobia for example)
- Patients with knee prosthesis
- Patients with coagulation disorders
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 |
|---|---|---|
| knee arthrocentesisarthrocentesis of the knee joint to gather a synovial fluid sample | Procedure or surgery | Patients with hemarthrosis, Patients without hemarthrosis |
| venipunctureAlso: blood drawPeripheral venipuncture to gather a blood sample | Procedure or surgery | Patients with hemarthrosis, Patients without hemarthrosis |
| MRI-scanMRI-scan of the knee | Diagnostic test | Patients with hemarthrosis, Patients without hemarthrosis |
| Physical examinationPhysical examination of the injured knee | Diagnostic test | Patients with hemarthrosis, Patients without hemarthrosis |
| KOOS questionnaireKOOS questionnaire of the injured knee | Other | Patients with hemarthrosis, Patients without hemarthrosis |
Primary outcome
Synovial fluid analysis
Time frame: Samples are taken at week 1, week 2, week 4, week 6 and week 8 after trauma
Analysis of changes in pro-inflammatory factors, erythrocytes (as measurement for hemarthrosis)
4 secondary outcomes
co-culture of synovial fluid with adipose stromal cells
Time frame: samples are taken at week 1, week 2, week 4, week 6 and week 8 after trauma
MRI-imaging
Time frame: At inclusion and 1 year after trauma
Physical examination
Time frame: Physical examination at week 1, week 2, week 4, week 6 and week 8 after trauma
Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire
Time frame: Questionnaires are taken at week 1, week 2, week 4, week 6 and week 8 after trauma
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
- Background: PubMed 24792943Riordan EA, Little C, Hunter D. Pathogenesis of post-traumatic OA with a view to intervention. Best Pract Res Clin Rheumatol. 2014 Feb;28(1):17-30. doi: 10.1016/j.berh.2014.02.001.
- Background: PubMed 17761605Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007 Oct;35(10):1756-69. doi: 10.1177/0363546507307396. Epub 2007 Aug 29.
- Background: PubMed 25232663Luc B, Gribble PA, Pietrosimone BG. Osteoarthritis prevalence following anterior cruciate ligament reconstruction: a systematic review and numbers-needed-to-treat analysis. J Athl Train. 2014 Nov-Dec;49(6):806-19. doi: 10.4085/1062-6050-49.3.35.
- Background: PubMed 15882559Ayral X, Pickering EH, Woodworth TG, Mackillop N, Dougados M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis -- results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage. 2005 May;13(5):361-7. doi: 10.1016/j.joca.2005.01.005.
- Background: PubMed 27890816Pulles AE, Mastbergen SC, Schutgens RE, Lafeber FP, van Vulpen LF. Pathophysiology of hemophilic arthropathy and potential targets for therapy. Pharmacol Res. 2017 Jan;115:192-199. doi: 10.1016/j.phrs.2016.11.032. Epub 2016 Nov 24.
- Background: PubMed 23821708Gupte C, St Mart JP. The acute swollen knee: diagnosis and management. J R Soc Med. 2013 Jul;106(7):259-68. doi: 10.1177/0141076813482831.
- Background: PubMed 28768528Wang Y, Shimmin A, Ghosh P, Marks P, Linklater J, Connell D, Hall S, Skerrett D, Itescu S, Cicuttini FM. Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial. Arthritis Res Ther. 2017 Aug 2;19(1):180. doi: 10.1186/s13075-017-1391-0.
- Background: PubMed 22961401ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, Jeanson J, Noel D, Casteilla L, Jorgensen C, van den Berg W, van Lent PL. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum. 2012 Nov;64(11):3604-13. doi: 10.1002/art.34626.
- Background: PubMed 24928317Schelbergen RF, van Dalen S, ter Huurne M, Roth J, Vogl T, Noel D, Jorgensen C, van den Berg WB, van de Loo FA, Blom AB, van Lent PL. Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8/A9 serum levels. Osteoarthritis Cartilage. 2014 Aug;22(8):1158-66. doi: 10.1016/j.joca.2014.05.022. Epub 2014 Jun 10.
- Background: PubMed 27217345Pers YM, Rackwitz L, Ferreira R, Pullig O, Delfour C, Barry F, Sensebe L, Casteilla L, Fleury S, Bourin P, Noel D, Canovas F, Cyteval C, Lisignoli G, Schrauth J, Haddad D, Domergue S, Noeth U, Jorgensen C; ADIPOA Consortium. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Stem Cells Transl Med. 2016 Jul;5(7):847-56. doi: 10.5966/sctm.2015-0245. Epub 2016 May 23.
- Individual participant dataSharing planned: Undecided
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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.
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 Post-Traumatic Osteoarthritis of Knee and Knee Injuries, run by Radboud University Medical Center at 1 site in Netherlands.
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 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: status not confirmed, as of the sponsor's last update on 18 Jan 2023. 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 Netherlands. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bob Evers, Drs/Msc (06-29630837, Bob.J.Evers@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Synovial fluid analysis (time frame: Samples are taken at week 1, week 2, week 4, week 6 and week 8 after trauma). 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 NCT05687331, which also lists 10 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 18 Jan 2023.