Clinical Efficacy of Exosome in Degenerative Meniscal Injury

Knee Injuries Clinical Trial

— KNEEXO  

Official title:

A Phase II Trial to Investigate Clinical Efficacy of Autologous Synovial Fluid Mesenchymal Stem Cell-Derived Exosome Application in Patients With Degenerative Meniscal Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05261360
• Other study ID #: 56733164/203
• Status: Recruiting
• Phase: Phase 2
• Start date: March 2022
• Est. completion date: March 2025

Study information

• Verified date: March 2022
• Source: Eskisehir Osmangazi University
• Contact: Ayla Eker Sariboyaci, AssocProfDr.
• Phone: +905382696420
• Email: aylaekersariboyaci[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Comparison of intra-articular administration of synovial fluid-derived mesenchymal stem cells-derived exosomes with synovial fluid-derived mesenchymal stem cells on the same patient.

Description:

Mesenchymal stem cell-derived exosomes will be developed and patented as an advanced technology platform as an autologous treatment protocol to repair damaged cartilage tissue. The fact that this treatment is obtained from an autologous source will significantly contribute to the literature in the field of personalized therapy (personalized medicine) and will pave the way for discoveries. Experiences from clinical trials may guide the use of MSC exosomes in other tissue and cell damaged pathologies and immune pathologies or chronic inflammatory diseases. This study was supported by a grant (1004, 20AG031) from The Scientific and Technological Research Council of Turkey (TUBITAK).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 2025
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 50 Years

Eligibility

Inclusion Criteria:

• Accepting the Informed Consent Form
• Degenerative meniscus damage grade 1, 2 or 3 on MRI in both right and left knees, and also the patient does not want surgical treatment
• Patients with the same degenerative meniscus grade in both knees
• Patients with ongoing pain
• Patients without a history of malignancy
• Absence of signs of unstable meniscus tear such as snagging or locking
• Patients with stage 0, 1 or 2 gonarthrosis according to Kellgren-Lawrence gonarthrosis staging
• Patients without lower extremity malalignment

Exclusion Criteria:

• Patients whose treatment method was explained and who did not accept the method
• Patients outside the working-age range
• Congenital lesion
• Patients requiring surgical treatment (e.g. bucket handle tear and locked knee)
• Active inflammatory or connective tissue disease is thought to affect the patient's pain (eg lupus, rheumatoid arthritis, fibromyalgia)
• Local or systemic infection
• Pregnant or breastfeeding women
• Active endocrine disorder that may affect the assessment of patient's pain (eg, hypothyroidism, diabetes)
• Active neurological disorder that may affect the assessment of the patient's pain (eg, peripheral neuropathy, multiple sclerosis)
• Active heart disease
• Presence of a pacemaker
• Conditions where MR-I is contraindicated
• Patients with stage 3 or 4 gonarthrosis according to Kellgren-Lawrence gonarthrosis staging
• Patients with lower extremity malalignment
• Patients with signs of unstable meniscus tear such as snagging or locking

Related Conditions & MeSH terms

• Arthralgia
• Knee Injuries
• Knee Pain Swelling
• Knee; Injury, Meniscus (Lateral) (Medial)
• Lacerations
• Meniscus Lesion
• Meniscus Tear
• Meniscus; Degeneration
• Tibial Meniscus Injuries
• Wounds and Injuries

Intervention

Drug:
• SF-MSC-EX
Intra-articular administration of synovial fluid-derived mesenchymal stem cells-derived exosomes
• SF-MSC
Intra-articular administration of synovial fluid-derived mesenchymal stem cells

Locations

Country	Name	City	State
Turkey	Eskisehir Osmangazi University	Eskisehir

Sponsors (2)

Lead Sponsor	Collaborator
Eskisehir Osmangazi University	The Scientific and Technological Research Council of Turkey

Country where clinical trial is conducted

Turkey, 

References & Publications (3)

Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. — View Citation

Pan H, Zhang P, Zhang Z, Yang Q. Arthroscopic partial meniscectomy combined with medical exercise therapy versus isolated medical exercise therapy for degenerative meniscal tear: A meta-analysis of randomized controlled trials. Int J Surg. 2020 Jul;79:222-232. doi: 10.1016/j.ijsu.2020.05.035. Epub 2020 Jun 6. Review. — View Citation

Tegner Y, Lysholm J. Rating systems in the evaluation of knee ligament injuries. Clin Orthop Relat Res. 1985 Sep;(198):43-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of Knee Functions	The functional evaluation of the participants will be evaluated on the Tegner-Lysholm knee scoring scale. In Tegner-Lysholm knee scoring, examinations for the knee joint (Limp, support, pain, instability, locking, swelling, stair-climbing, and squatting) will be evaluated, and a maximum of 100 and a minimum of 0 points will be given. According to the evaluation, <65 points are interpreted as bad, 65-83 points as fair, 84-90 points as good, >90 points as excellent. Scores will be recorded by being examined before treatment and at the 6th, and 12th months after treatment. Knee functions of the control group will be evaluated simultaneously, and the effects of treatments on knee function will be determined.	Up to 12th months
Primary	Evaluation of Physical Activity	The physical activity evaluation of the participants will be evaluated with the IPAQ (international physical activity questionnaire) short form. IPAQ short form will be evaluated and recorded before treatment and at the 6th, and 12th months after treatment. The control group's physical activity will be evaluated simultaneously, and the effects of treatments on physical activity will be determined.	Up to 12th months
Primary	Evaluation of Pain	Pain assessment of the participants will be evaluated with VAS (Visual analog scale). The VAS will be evaluated and recorded before treatment and at the 6th, and 12th months after treatment. The physical activity of the control group will be evaluated simultaneously, and the effects of treatments on pain will be determined.	Up to 12th months
Primary	Evaluation of Radiological Images	Participants will receive knee x-ray imaging and knee magnetic resonance imaging before treatment. The same radiological imaging will be performed at the 6th and 12th months after the treatment. At the same time, the same radiological imaging will be performed on the control group, and the effects of treatments on radiological imaging will be evaluated.	Up to 12th months
Primary	Evaluation of Cytokine Levels and Cytokine Genes Analyzes	Before treatment and at the 6th and 12th months after treatment, cytokine levels (IL-10, IL-6, TNF-a, IL-8, IL-1ß, IFN-?, IL-2, IL-4, IL-13, MCP-1, VEGF) and gene analyzes (IL-10, IL-6, TNF-a, IL-8, IL-1ß, IFN-?, IL-2, IL-4, IL-13, MCP-1, IL-1ra, MIP-1b, CTGF, TGFß3, BMP-2, BMP-4, IGF-1, IGF-2, PDGF, EGF, and VEGF genes) will be checked in the samples taken from the synovial fluid and blood. Samples will be taken from the control group along with the treatment group. In this way, the effects of treatments on cytokine levels will be evaluated.	Up to 12th months
Primary	Evaluation of Edema	Edema in both knees will be measured using a tape measure by marking the midpoints of both patellae. Pre-treatment measurements will be recorded. Measurements of both knees will be recorded at 6 months and 12 months after treatment. The knees of the patients not receiving treatment will be measured simultaneously, and the changes will be compared.	Up to 12th months
Primary	Evaluation of Knee Joint Range of Motion	The range of motion of both knees will be measured using the "Baseline Digital Absolute+Axis Goniometer." Knee extension measurements will be made with the patient in the supine position and flexion in the prone position. Pre-treatment measurements will be recorded. Post-treatment 6th and 12th-month measurements will also be recorded. Measurements of patients not receiving treatment will be recorded simultaneously, and changes will be compared.	Up to 12th months
Primary	Monitoring of treatment-related complications	Adverse effects and complications will be observed in the treatment group, except for the expected local reactions (redness, swelling, bruising, etc.) after the application.	Up to 12th months