Knee; Injury, Meniscus (Lateral) (Medial)Phase 2KNEEXONCT05261360
Clinical Efficacy of Exosome in Degenerative Meniscal Injury
A Phase 2 study testing SF-MSC-EX and SF-MSC in people with Knee; Injury, Meniscus (Lateral) (Medial) and Meniscus Tear, run by Eskisehir Osmangazi University at 1 site in Turkey (Türkiye).
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. Read more about this study
- Who is it for?
- Ages 30 to 50 years
- Conditions the study is for
- Knee; Injury, Meniscus (Lateral) (Medial), Meniscus Tear, Meniscus Lesion
- What is being tested?
- SF-MSC-EX and SF-MSC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- Mar 2022to Mar 2025
- Phase
- Phase 2
- 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 30 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Eskisehir Osmangazi University
Eskişehir, 26040
Ayla Eker Sariboyaci, AssocProfDr, +905382696420, aylaekersariboyaci@yahoo.com
Ulukan Inan, Prof.Dr.
About this study
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
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.
Read the detailed 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).
- Conditions
- Knee; Injury, Meniscus (Lateral) (Medial), Meniscus Tear, Meniscus Lesion, Meniscus; Degeneration, Meniscus; Laceration, Meniscus Injury, Tibial
- Being tested
- SF-MSC-EX, SF-MSC
- Keywords
- Meniscal injury, Exosome, Mesenchymal Stem Cell, Synovial Fluid, Regeneration
- Medical subject headings
- Wounds and Injuries, Lacerations, Tibial Meniscus Injuries, Knee Injuries, Arthralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SF-MSC-EXDrug
Also called Intraarticular Exosome Treatment
Intra-articular administration of synovial fluid-derived mesenchymal stem cells-derived exosomes
SF-MSCDrug
Also called Intraarticular Stem Cell Treatment
Intra-articular administration of synovial fluid-derived mesenchymal stem cells
| Study group | Role | What they receive |
|---|---|---|
| SF-MSC-EX Treatment Group (Experimental group's left knees) | Experimental | The left knee will receive 1 million cells/kg SF-MSC-EX (Synovial fluid mesenchymal stem cell-derived exosome) by intra-articular injection method. Receives: Drug: SF-MSC-EX |
| SF-MSC Treatment Group (Experimental group's right knees) | Experimental | The right knee will receive 1 million cells/kg SF-MSC (Synovial fluid-derived mesenchymal stem cell) by intra-articular injection method. Receives: Drug: SF-MSC |
| Control Group | No intervention | Participants who received no treatment were defined as the control group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 12th months
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.
Measured: Up to 12th months
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.
Measured: Up to 12th months
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.
Measured: Up to 12th months
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-α, IL-8, IL-1β, IFN-ɣ, IL-2, IL-4, IL-13, MCP-1, VEGF) and gene analyzes (IL-10, IL-6, TNF-α, IL-8, IL-1β, IFN-ɣ, IL-2, IL-4, IL-13, MCP-1, IL-1ra, MIP-1b, CTGF, TGFβ3, 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.
Measured: Up to 12th months
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.
Measured: Up to 12th months
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.
Measured: Up to 12th months
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.
Measured: Up to 12th months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2022
- Study startMar 2022 (estimated)
- Primary completionMar 2024 (estimated)
- Study completionMar 2025 (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; Injury, Meniscus (Lateral) (Medial)Studies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study was planned as three arms. One arm will be the control group, and the other two arms will be the experimental group. The control group defines the group that did not receive treatment. Those in the experimental group, who are the participants other than the control group, will occur in both experimental groups. SF-MSC (synovial fluid-derived mesenchymal stem cells) will be applied intraarticularly to the experimental group's right knee, and the experimental group's right knee will be included in the SF-MSC treatment group. SF-MSC-EX (synovial fluid-derived mesenchymal stem cells-derived exosomes) will be applied intraarticularly to the experimental group's left knee, and the experimental group's left knee will be included in the SF-MSC-EX treatment group.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eskisehir Osmangazi University
- Sponsor type
- University, hospital or other
- Collaborators
- The Scientific and Technological Research Council of Turkey
- Responsible party
- Principal investigator, Ayla Eker Sariboyaci, Eskisehir Osmangazi University
- Investigators
- Ayla Eker Sarıboyacı, AssocProfDr., Study chair, Cell Therapy and Stem Cell Production Application and Research Center (ESTEM)Onur Uysal, AssocProfDr., Study director, Cell Therapy and Stem Cell Production Application and Research Center (ESTEM)Ulukan İnan, ProfDr., Principal investigator, Eskisehir Osmangazi University Faculty of Medicine Department of Orthopedy and Traumatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05261360
- Sponsor's protocol ID
- 56733164/203
- Acronym
- KNEEXO
- Status last verified
- Mar 2022
- First submitted
- 1 Nov 2021
- Last updated
- 4 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Results will be reported after the completion of the study.
Publications
Tegner Y, Lysholm J. Rating systems in the evaluation of knee ligament injuries. Clin Orthop Relat Res. 1985 Sep;(198):43-9.
PubMed 4028566Craig CL, Marshall AL, Sjostrom 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. doi: 10.1249/01.MSS.0000078924.61453.FB.
PubMed 12900694Pan 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.
PubMed 32522685
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05261360
- Acronym / sponsor ID
- KNEEXO / 56733164/203
- Conditions
- Knee; Injury, Meniscus (Lateral) (Medial), Meniscus Tear, Meniscus Lesion, Meniscus; Degeneration, Meniscus; Laceration, Meniscus Injury, Tibial
- Keywords
- Meniscal injury, Exosome, Mesenchymal Stem Cell, Synovial Fluid, Regeneration
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Eskisehir Osmangazi UniversityUniversity, hospital or other
- Collaborators
- The Scientific and Technological Research Council of Turkey
- Study start
- Mar 2022 (estimated)
- Primary completion
- Mar 2024 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 2 Mar 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.
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.
Detailed 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study was planned as three arms. One arm will be the control group, and the other two arms will be the experimental group. The control group defines the group that did not receive treatment. Those in the experimental group, who are the participants other than the control group, will occur in both experimental groups. SF-MSC (synovial fluid-derived mesenchymal stem cells) will be applied intraarticularly to the experimental group's right knee, and the experimental group's right knee will be included in the SF-MSC treatment group. SF-MSC-EX (synovial fluid-derived mesenchymal stem cells-derived exosomes) will be applied intraarticularly to the experimental group's left knee, and the experimental group's left knee will be included in the SF-MSC-EX treatment group.
| Arm | Type | Receives |
|---|---|---|
| SF-MSC-EX Treatment Group (Experimental group's left knees) | Experimental | Drug: SF-MSC-EXThe left knee will receive 1 million cells/kg SF-MSC-EX (Synovial fluid mesenchymal stem cell-derived exosome) by intra-articular injection method. |
| SF-MSC Treatment Group (Experimental group's right knees) | Experimental | Drug: SF-MSCThe right knee will receive 1 million cells/kg SF-MSC (Synovial fluid-derived mesenchymal stem cell) by intra-articular injection method. |
| Control Group | No intervention | –Participants who received no treatment were defined as the control group. |
Who may qualify
- Ages
- 30 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
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 |
|---|---|---|
| SF-MSC-EXAlso: Intraarticular Exosome TreatmentIntra-articular administration of synovial fluid-derived mesenchymal stem cells-derived exosomes | Drug | SF-MSC-EX Treatment Group (Experimental group's left knees) |
| SF-MSCAlso: Intraarticular Stem Cell TreatmentIntra-articular administration of synovial fluid-derived mesenchymal stem cells | Drug | SF-MSC Treatment Group (Experimental group's right knees) |
Primary outcome
Evaluation of Knee Functions
Time frame: Up to 12th months
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.
Evaluation of Physical Activity
Time frame: Up to 12th months
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.
Evaluation of Pain
Time frame: Up to 12th months
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.
Evaluation of Radiological Images
Time frame: Up to 12th months
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.
Evaluation of Cytokine Levels and Cytokine Genes Analyzes
Time frame: Up to 12th months
Before treatment and at the 6th and 12th months after treatment, cytokine levels (IL-10, IL-6, TNF-α, IL-8, IL-1β, IFN-ɣ, IL-2, IL-4, IL-13, MCP-1, VEGF) and gene analyzes (IL-10, IL-6, TNF-α, IL-8, IL-1β, IFN-ɣ, IL-2, IL-4, IL-13, MCP-1, IL-1ra, MIP-1b, CTGF, TGFβ3, 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.
Evaluation of Edema
Time frame: Up to 12th months
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.
Evaluation of Knee Joint Range of Motion
Time frame: Up to 12th months
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.
Monitoring of treatment-related complications
Time frame: Up to 12th months
Adverse effects and complications will be observed in the treatment group, except for the expected local reactions (redness, swelling, bruising, etc.) after the application.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2022.
- Background: PubMed 4028566Tegner Y, Lysholm J. Rating systems in the evaluation of knee ligament injuries. Clin Orthop Relat Res. 1985 Sep;(198):43-9.
- Background: PubMed 12900694Craig CL, Marshall AL, Sjostrom 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. doi: 10.1249/01.MSS.0000078924.61453.FB.
- Background: PubMed 32522685Pan 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.
- Individual participant dataSharing planned: No. Results will be reported after the completion of the study.
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.
Ayla Eker Sarıboyacı, AssocProfDr. study chair
Cell Therapy and Stem Cell Production Application and Research Center (ESTEM)
Onur Uysal, AssocProfDr. study director
Cell Therapy and Stem Cell Production Application and Research Center (ESTEM)
Ulukan İnan, ProfDr. principal investigator
Eskisehir Osmangazi University Faculty of Medicine Department of Orthopedy and Traumatology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SF-MSC-EX and SF-MSC in people with Knee; Injury, Meniscus (Lateral) (Medial) and Meniscus Tear, run by Eskisehir Osmangazi 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 8 inclusion and 15 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 4 Mar 2022. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Ayla Eker Sarıboyacı, AssocProfDr. (+905382696420, aylaekersariboyaci@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of Knee Functions (time frame: Up to 12th months). The study lists 8 primary outcomes in all. 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 NCT05261360, 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 4 Mar 2022.