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Clinical Efficacy of Exosome in Degenerative Meniscal Injury (KNEEXO)

Primary Purpose

Knee; Injury, Meniscus (Lateral) (Medial), Meniscus Tear, Meniscus Lesion

Status

Recruiting

Phase

Phase 2

Locations

Turkey

Study Type

Interventional

Intervention

SF-MSC-EX

SF-MSC

About this trial

This is an interventional treatment trial for Knee; Injury, Meniscus (Lateral) (Medial) focused on measuring Meniscal injury, Exosome, Mesenchymal Stem Cell, Synovial Fluid, Regeneration

Eligibility Criteria

30 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Eskisehir Osmangazi UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Arm Label

SF-MSC-EX Treatment Group (Experimental group's left knees)

SF-MSC Treatment Group (Experimental group's right knees)

Control Group

Arm Description

The left knee will receive 1 million cells/kg SF-MSC-EX (Synovial fluid mesenchymal stem cell-derived exosome) by intra-articular injection method.

The right knee will receive 1 million cells/kg SF-MSC (Synovial fluid-derived mesenchymal stem cell) by intra-articular injection method.

Participants who received no treatment were defined as the control group.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT05261360

First Posted

November 1, 2021

Last Updated

March 3, 2022

Sponsor

Eskisehir Osmangazi University

Collaborators

The Scientific and Technological Research Council of Turkey

1. Study Identification

Unique Protocol Identification Number

NCT05261360

Brief Title

Clinical Efficacy of Exosome in Degenerative Meniscal Injury

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

March 2022 (Anticipated)

Primary Completion Date

March 2024 (Anticipated)

Study Completion Date

March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Eskisehir Osmangazi University

Collaborators

The Scientific and Technological Research Council of Turkey

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Knee; Injury, Meniscus (Lateral) (Medial), Meniscus Tear, Meniscus Lesion, Meniscus; Degeneration, Meniscus; Laceration, Meniscus Injury, Tibial, Knee Injuries, Knee Pain Swelling, Arthralgia

Keywords

Meniscal injury, Exosome, Mesenchymal Stem Cell, Synovial Fluid, Regeneration

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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)

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

SF-MSC-EX Treatment Group (Experimental group's left knees)

Arm Type

Experimental

Arm Description

The left knee will receive 1 million cells/kg SF-MSC-EX (Synovial fluid mesenchymal stem cell-derived exosome) by intra-articular injection method.

Arm Title

SF-MSC Treatment Group (Experimental group's right knees)

Arm Type

Experimental

Arm Description

The right knee will receive 1 million cells/kg SF-MSC (Synovial fluid-derived mesenchymal stem cell) by intra-articular injection method.

Arm Title

Control Group

Arm Type

No Intervention

Arm Description

Participants who received no treatment were defined as the control group.

Intervention Type

Drug

Intervention Name(s)

SF-MSC-EX

Other Intervention Name(s)

Intraarticular Exosome Treatment

Intervention Description

Intra-articular administration of synovial fluid-derived mesenchymal stem cells-derived exosomes

Intervention Type

Drug

Intervention Name(s)

SF-MSC

Other Intervention Name(s)

Intraarticular Stem Cell Treatment

Intervention Description

Intra-articular administration of synovial fluid-derived mesenchymal stem cells

Primary Outcome Measure Information:

Title

Evaluation of Knee Functions

Description

Time Frame

Up to 12th months

Title

Evaluation of Physical Activity

Description

Time Frame

Up to 12th months

Title

Evaluation of Pain

Description

Time Frame

Up to 12th months

Title

Evaluation of Radiological Images

Description

Time Frame

Up to 12th months

Title

Evaluation of Cytokine Levels and Cytokine Genes Analyzes

Description

Time Frame

Up to 12th months

Title

Evaluation of Edema

Description

Time Frame

Up to 12th months

Title

Evaluation of Knee Joint Range of Motion

Description

Time Frame

Up to 12th months

Title

Monitoring of treatment-related complications

Description

Adverse effects and complications will be observed in the treatment group, except for the expected local reactions (redness, swelling, bruising, etc.) after the application.

Time Frame

Up to 12th months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ayla Eker Sarıboyacı, AssocProfDr.

Phone

+905382696420

aylaekersariboyaci@yahoo.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ayla Eker Sarıboyacı, AssocProfDr.

Organizational Affiliation

Cell Therapy and Stem Cell Production Application and Research Center (ESTEM)

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Onur Uysal, AssocProfDr.

Organizational Affiliation

Cell Therapy and Stem Cell Production Application and Research Center (ESTEM)

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Ulukan İnan, ProfDr.

Organizational Affiliation

Eskisehir Osmangazi University Faculty of Medicine Department of Orthopedy and Traumatology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Eskisehir Osmangazi University

City

Eskisehir

ZIP/Postal Code

26040

Country

Turkey

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ayla Eker Sariboyaci, AssocProfDr

Phone

+905382696420

aylaekersariboyaci@yahoo.com

First Name & Middle Initial & Last Name & Degree

Ulukan Inan, Prof.Dr.

First Name & Middle Initial & Last Name & Degree

Ayla Eker Sariboyaci, AssocProfDr

First Name & Middle Initial & Last Name & Degree

Onur Uysal, AssocProfDr

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Results will be reported after the completion of the study.

Citations:

PubMed Identifier

4028566

Citation

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

Results Reference

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PubMed Identifier

12900694

Citation

Craig 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.

Results Reference

background

PubMed Identifier

32522685

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.

Results Reference

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Clinical Efficacy of Exosome in Degenerative Meniscal Injury

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