Changes in the Immunomodulatory Properties of Adipose Stromal Cells Due to Hemarthrosis After Knee Injury

Knee Injuries Clinical Trial

— CASH  

Official title:

Changes in the Immunomodulatory Properties of Adipose Stromal Cells Due to Hemarthrosis After Knee Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05687331
• Other study ID #: NL77974.091.21
• Status: Recruiting
• Start date: April 5, 2022
• Est. completion date: April 1, 2024

Study information

• Verified date: December 2022
• Source: Radboud University Medical Center
• Contact: Bob Evers, Drs/Msc
• Phone: 06-29630837
• Email: Bob.J.Evers[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Recently suffered an injury of the index knee (rotational or hyperextension)

• A swollen joint

• Inability to mobilise

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hemarthrosis
• Knee Injuries
• Osteoarthritis, Knee
• Post-Traumatic Osteoarthritis of Knee
• Wounds and Injuries

Intervention

Procedure:
• knee arthrocentesis
arthrocentesis of the knee joint to gather a synovial fluid sample
• venipuncture
Peripheral venipuncture to gather a blood sample

Diagnostic Test:
• MRI-scan
MRI-scan of the knee
• Physical examination
Physical examination of the injured knee

Other:
• KOOS questionnaire
KOOS questionnaire of the injured knee

Locations

Country	Name	City	State
Netherlands	Radboud umc	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (10)

Ayral 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. — View Citation

Gupte 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. — View Citation

Lohmander 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. — View Citation

Luc 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. — View Citation

Pers 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. — View Citation

Pulles 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. — View Citation

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. — View Citation

Schelbergen 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. — View Citation

ter 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. — View Citation

Wang 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Synovial fluid analysis	Analysis of changes in pro-inflammatory factors, erythrocytes (as measurement for hemarthrosis)	Samples are taken at week 1, week 2, week 4, week 6 and week 8 after trauma
Secondary	co-culture of synovial fluid with adipose stromal cells	Assessment of changes in cytotoxity of hemarthrosis in synovial fluid on adipose stromal cells	samples are taken at week 1, week 2, week 4, week 6 and week 8 after trauma
Secondary	MRI-imaging	MRI-images to determine post-traumatic changes in the articulate cartilage	At inclusion and 1 year after trauma
Secondary	Physical examination	Assessment of changes in swelling, warmth and appearance of the skin	Physical examination at week 1, week 2, week 4, week 6 and week 8 after trauma
Secondary	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.	Questionnaires are taken at week 1, week 2, week 4, week 6 and week 8 after trauma