Platelet-rich Plasma and Synovial Cytokines in Knee Osteoarthritis

Assessments of Therapeutic Effects of Platelet-rich Plasma in Knee Osteoarthritis: Possible Role of Inflammatory Cytokines

A prospective study was performed on 90 patients were included and categorized into mild (30 cases, moderate (30 cases) and severe (30 cases) knee OA. Three intra-articular (I.A) injections of PRP, 2 weeks a part, were received. Pain score and MRI Osteoarthritis Knee Score (MOAKS) were assessed. Serial synovial fluid cytokines assays in the form of Tumor necrosis factor-α (TNF-α) and Macrophage migration inhibitory factor (MIF), were performed using commercially available ELISA assay kits. The assays were performed pre-injection (S1), two weeks from the 1st I.A injection and two weeks from the 2nd I.A injection (S3) for all included patients.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Intra-articular injection of platelet-rich plasma

Detailed Description

Background: Osteoarthritis (OA) is a multifactorial disease that commonly affects the knee. Tumor necrosis factor-α (TNF-α) is able to regulate inflammation in OA. Macrophage migration inhibitory factor (MIF) may be involved in the pathophysiology of arthritis. Platelet-rich plasma (PRP) may reduce pain associated with OA. The current study aimed to assess the possible therapeutic effects of PRP in patients with knee OA of various severities.

Methods: A prospective study was performed on 90 patients were included and categorized into mild (30 cases, moderate (30 cases) and severe (30 cases) knee OA. Three intra-articular (I.A) injections of PRP, 2 weeks a part, were received. Pain score and MRI Osteoarthritis Knee Score (MOAKS) were assessed. Serial synovial fluid cytokines assays in the form of Tumor necrosis factor-α (TNF-α) and Macrophage migration inhibitory factor (MIF), were performed using commercially available ELISA assay kits. The assays were performed pre-injection (S1), two weeks from the 1st I.A injection and two weeks from the 2nd I.A injection (S3) for all included patients.

PRP preparation: The PRP needed for IA injection has been prepared under complete aseptic conditions. In order to avoid the effect of food intake on purified PRP, on the day of injection the patients were instructed to fast for 4 hours before blood collection. Approximately 20 mL of venous blood were drawn from the antecubital vein using an aseptic technique in an effort to avoid irritation and trauma to the platelets. Anti-coagulated blood was obtained in ten extraction tubes (2 mL each), containing sodium citrate. The tubes were then centrifuged at 2100 rpm at room temperature for 8 minutes to separate the blood in each tube into the citrated plasma, the buffy coat and the residual red blood cells ( RBCs) . Using a pipette, the PRP situated just above the selectively precipitated RBCs but not including the buffy coat was carefully aspirated from each tube. In each affected joint, 10-mL PRP samples (from the collected venous blood) were used for IA injection . For each intra-articular injection new fresh PRP samples were made from the patients.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Qena, Egypt, 83523
    • Faculty of medicine, South Valley University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients have unilateral knee OA

Exclusion Criteria:

• Polyarticular disease.
• Knee arthroscopy in the previous year.
• HA or steroid IA penetration in the preceding 3 months.
• History of infectious disease and autoimmune disorders such as diabetes, rheumatoid arthritis.
• Hematologic diseases (coagulopathy).
• Serious cardiovascular diseases , infections or immunodepression.
• Anticoagulant therapy or an anti-aggregating agent.
• Uuse of non-steroidal anti-inflammatory drugs 2 weeks prior to blood sampling.
• < 10 g / dL of hemoglobin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Mild knee osteoarthritis; 30 patients had mild knee osteoarthritis	Drug: Intra-articular injection of platelet-rich plasma; The patient was put in 20 degree flexion in supine position with the knee. Under aseptic conditions, a 21-gage needle was used to inject 5 mL of PRP into the suprapatellar knee joint pouch, using a superolateral method. Local anesthetics were not used. Patients were instructed after the injection to refrain from physical exercise for at least 24 hours but no restriction was specified regarding activities of daily living. Three IA-PRP injections were administered at 2-week intervals. The same physician who was engaged in selecting and testing participants did the injections; Other Names: PRP injection
Active Comparator: Moderate knee osteoarthritis; 30 patients had moderate knee osteoarthritis	Drug: Intra-articular injection of platelet-rich plasma; The patient was put in 20 degree flexion in supine position with the knee. Under aseptic conditions, a 21-gage needle was used to inject 5 mL of PRP into the suprapatellar knee joint pouch, using a superolateral method. Local anesthetics were not used. Patients were instructed after the injection to refrain from physical exercise for at least 24 hours but no restriction was specified regarding activities of daily living. Three IA-PRP injections were administered at 2-week intervals. The same physician who was engaged in selecting and testing participants did the injections; Other Names: PRP injection
Active Comparator: Severe knee osteoarthritis; 30 patients had severe knee osteoarthritis	Drug: Intra-articular injection of platelet-rich plasma; The patient was put in 20 degree flexion in supine position with the knee. Under aseptic conditions, a 21-gage needle was used to inject 5 mL of PRP into the suprapatellar knee joint pouch, using a superolateral method. Local anesthetics were not used. Patients were instructed after the injection to refrain from physical exercise for at least 24 hours but no restriction was specified regarding activities of daily living. Three IA-PRP injections were administered at 2-week intervals. The same physician who was engaged in selecting and testing participants did the injections; Other Names: PRP injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Pain Scores in patients with various severities of knee OA following intra-articular injection of PRP at 0, and 2 weeks from the second injection (0,4 weeks).	Using Visual Analog Scale (VAS) score to assess the pain score in patients with knee osteoarthritis will be done twice , pre-intra-articular injection of PRP and 2 weeks from the second I.A injection of PRP. The VAS is a common tool that uses a 10 cm scale for pain intensity measurement, where 0= no pain and 10= unable to move.	one year
Changes in the synovial fluid concentration of the TNF-α and MIF levels folllowing PRP injection, using ELISA assay kits.	Using ELISA assay kits, synovial fluid concentration of both TNF-α and MIF levels will be measured three times for the same patient (before injection, 2 weeks from the first injection and 2 weeks from the second injection) to explore the serial changes in their levels following IA i injection PRP.	one year
Changes in MRI Osteoarthritis Knee Score (MOAKS) in patients with various severities of knee OA following intra-articular injection of PRP at 0, and 2 weeks from the second injection (0,4 weeks).	Regarding MRI knee score will be done twice , pre-intra-articular injection of PRP and 2 weeks from the second I.A injection of PRP. For assessment of both bone marrow abnormality or patella-femoral cartilage volume (grade I (mild if the lesion involves ˂33% of subregional volume); grade II (Moderate: if the lesion involves 33%- 66% of subregional volume), and grade III (severe: if the lesion involves ˃ 66% of subregional volume).Regarding synovitis: grade 1 (mild or small - fluid continuous in the retropatellar space); grade 2 (Moderate or medium - slight convexity of the suprapatellar bursa), and grade 3 (severe or large - evidence of capsular distension ). Meniscal desintegrity score of 0-3 applied for amount of extrusion in 4 locations: medial meniscus (medial and anterior extrusion) and lateral meniscus (medial and anterior extrusion).	one year
Assess the correlations of synovial fluid TNF-α and MIF levels with both pain and radiological scores will performed among these patients.	Correlate visual Analog pain Scale and MRI Osteoarthritis Knee Score with the pre-injection cytokine synovial levels and synovial level values 2 weeks from the second IA injection of PRP	one year

Collaborators and Investigators

• Sponsor: South Valley University
• Investigators: Principal Investigator: Mohammed H Hassan, MD, Faculty of Medicine- South Valley University

Publications and helpful links

General Publications

• Taniguchi Y, Yoshioka T, Kanamori A, Aoto K, Sugaya H, Yamazaki M. Intra-articular platelet-rich plasma (PRP) injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population: a phase I and IIa clinical trial. Nagoya J Med Sci. 2018 Feb;80(1):39-51. doi: 10.18999/nagjms.80.1.39.
• Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, Roemer FW. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthritis Cartilage. 2011 Aug;19(8):990-1002. doi: 10.1016/j.joca.2011.05.004. Epub 2011 May 23. Erratum In: Osteoarthritis Cartilage. 2011 Sep;19(9):1168.
• Katz J, Melzack R. Measurement of pain. Surg Clin North Am. 1999 Apr;79(2):231-52. doi: 10.1016/s0039-6109(05)70381-9.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): January 31, 2020
• Study Completion (Actual): March 14, 2020

Study Registration Dates

• First Submitted: February 5, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Knee osteoarthritis; pain score; Platelet rich plasma; synovial fluid; MRI Osteoarthritis Knee Score; tumor necrosis factor-α; macrophage migration inhibitory factor
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: SVU-QFM-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No