The Effects of Intra-articular and Peri-articular Platelet-rich Plasma (PRP) Injections ın Chronic Knee Osteoarthritis

NCT07339137 | Recruiting

• 1 other identifier: E2-25-9883
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to evaluate and compare the effectiveness of ultrasound-guided combined intra-articular and peri-articular platelet-rich plasma (PRP) injections with intra-articular PRP injections alone in patients with chronic knee osteoarthritis (OA). The study specifically examines the effects of these treatment approaches on pain, physical function, activities of daily living, and structural parameters, including medial collateral ligament (MCL) thickness and distal femoral cartilage thickness. Osteoarthritis is a degenerative joint disease characterized by progressive cartilage erosion, osteophyte formation, and subchondral sclerosis, leading to pain, stiffness, and functional disability. It is the most common form of arthritis and a leading cause of disability worldwide, affecting approximately 300 million individuals. Although the knee is the most frequently involved joint, OA is now recognized as a whole-joint disease, involving not only cartilage degeneration but also pathological changes in subchondral bone, synovium, and surrounding extra-articular structures. Platelet-rich plasma is an autologous concentration of platelets suspended in a small volume of plasma and contains a variety of bioactive growth factors, such as transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). These factors play a crucial role in promoting cell proliferation, angiogenesis, and tissue repair. In knee OA, PRP has been shown to reduce matrix metalloproteinase (MMP) activity, particularly MMP-13, enhance endogenous hyaluronic acid production, and support chondrogenesis. Although intra-articular PRP injections are widely accepted as a safe and effective treatment and have demonstrated superiority over placebo and hyaluronic acid in long-term follow-up studies, most existing research has focused exclusively on intra-articular applications. Knee OA is a multifactorial condition frequently associated with extra-articular pathologies, including ligament laxity, peri-articular edema, and soft tissue inflammation. Limiting treatment to the intra-articular space alone may therefore overlook these important contributors to pain and functional impairment. Emerging evidence suggests that a combined treatment approach targeting both intra-articular and peri-articular structures may provide superior outcomes in terms of pain reduction and functional improvement. This prospective randomized controlled trial will include 42 patients aged 40-65 years with chronic knee OA classified as Kellgren-Lawrence grade 2 or 3. Participants will be randomly assigned to one of three groups: a control group receiving conservative treatment only (exercise therapy and lifestyle modifications), a group receiving conservative treatment plus ultrasound-guided intra-articular PRP injections, and a third group receiving conservative treatment plus combined ultrasound-guided intra-articular and peri-articular PRP injections targeting the MCL and pes anserinus regions. Clinical outcomes will be assessed using validated instruments, including the Visual Analog Scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Short Form-36 (SF-36) Quality of Life Scale. In addition, ultrasonographic measurements of MCL thickness and distal femoral cartilage thickness will be performed to evaluate structural changes. By investigating the additional value of peri-articular PRP injections, this study aims to contribute to the development of more comprehensive and effective injection protocols for the management of chronic knee osteoarthritis.

Conditions

Platelet Rich Plasma Injection; Gonarthrosis; Ultrasonography

Keywords

knee osteoarthritis; periarticular; PRP; USG; Femoral Cartilage; Medial Collateral Ligament

Outcome Measures

Primary Outcomes (2)

• VAS (Visual Analog Scale)

  The visual analog scale (VAS) is a widely accepted measurement tool in the scientific literature used to quantify subjective variables that cannot be directly measured numerically. It consists of a 100-mm horizontal line, with each end representing the extreme limits of the parameter being assessed, ranging from no pain to very severe pain. Patients are asked to mark the point on the line that best reflects their current pain intensity. The distance measured from the no-pain endpoint to the patient's mark indicates the level of pain. The VAS is a safe, easy-to-use, and valid instrument for assessing pain intensity.

  Pain measurements using the VAS will be obtained at baseline (week 0), 1 week after completion of treatment (week 3), and 3 months after completion of treatment (week 14).

• WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index)

  The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a valid and reliable disease-specific instrument widely used to assess disability in patients with osteoarthritis. It consists of three subscales: pain (5 items), stiffness (2 items), and physical function (17 items). Each item is scored on a Likert scale ranging from 0 to 4, reflecting the level of impairment. Subscale scores are calculated separately and combined to yield a total score ranging from 0 to 100, with higher scores indicating increased pain and stiffness and greater impairment in physical function. The Turkish validity and reliability of the WOMAC were established by Tüzün and colleagues.

  The WOMAC will be assessed at baseline (week 0), 1 week after completion of treatment (week 3), and 3 months after completion of treatment (week 14).

Secondary Outcomes (3)

• SF-36 (Short Form 36 Health Survey)

  Quality of life will be assessed using the SF-36 at baseline (week 0), 1 week after completion of treatment (week 3), and 3 months after completion of treatment (week 14).

• Distal femoral cartilage thickness

  Distal femoral cartilage thickness will be measured at baseline (week 0), 1 week after completion of treatment (week 3), and 3 months after completion of treatment (week 14) for each participant.

• Medial Collateral Ligament thickness

  Medial collateral ligament (MCL) thickness will be measured at baseline (week 0), 1 week after completion of treatment (week 3), and 3 months after completion of treatment (week 14) for each participant.

Study Arms (3)

Control Group

ACTIVE COMPARATOR

Patients receiving guidance on conservative exercise therapy and lifestyle chang

Behavioral: Conservative Therapy

Intra-articular PRP

ACTIVE COMPARATOR

Patients receiving intra-articular PRP therapy in addition to guidance on conservative exercise therapy and lifestyle chang

Behavioral: Conservative Therapy; Procedure: Intra-Articular PRP

Combinated PRP (Intra and peri-articular PRP)

ACTIVE COMPARATOR

Patients receiving combined (periarticular and intraarticular PRP therapy) in addition to guidance on conservative exercise therapy and lifestyle chang

Behavioral: Conservative Therapy; Procedure: Intra-Articular PRP; Procedure: Peri-Articular PRP

Interventions

Conservative Therapy BEHAVIORAL

Patients will receive guidance on conservative exercise therapy and lifestyle modifications. Exercise instruction forms will be provided, and patients will be shown how to perform the exercises correctly. Strengthening, stretching, and joint range of motion exercises targeting the quadriceps and hamstring muscle groups will be performed twice daily for 10 repetitions throughout the treatment period. Adherence will be monitored during follow-up visits.

Combinated PRP (Intra and peri-articular PRP); Control Group; Intra-articular PRP

Intra-Articular PRP PROCEDURE

Patients will receive intra-articular platelet-rich plasma (PRP) injections three times at one-week intervals. Following the PRP injections, patients will receive standard post-procedure recommendations, including resting the knee joint for 1-2 days, avoiding aggressive exercise, refraining from using nonsteroidal anti-inflammatory drugs (NSAIDs), and applying warm compresses as needed.

Combinated PRP (Intra and peri-articular PRP); Intra-articular PRP

Peri-Articular PRP PROCEDURE

Patients will receive peri-articular platelet-rich plasma (PRP) injections three times at one-week intervals. Following the PRP injections, patients will receive standard post-procedure recommendations, including resting the knee joint for 1-2 days, avoiding aggressive exercise, refraining from using nonsteroidal anti-inflammatory drugs (NSAIDs), and applying warm compresses as needed. Peri-articular injections will be administered under ultrasound (USG) guidance to the origin and insertion sites of the medial collateral ligament (MCL), relevant joint areas, and the insertion points of the pes anserinus tendons.

Combinated PRP (Intra and peri-articular PRP)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 40 and 65 years.
• Patients with significant medial knee pain who have not responded to conservative treatment for at least 3 months.
• Patients diagnosed with knee osteoarthritis according to the American College of Rheumatology (ACR) criteria and with Kellgren-Lawrence grade 2 or 3 radiographic osteoarthritis.
• Intact cognitive function.
• Willingness to participate in the study and provide signed informed consent.
• Visual Analog Scale (VAS) score of 4 or higher.

You may not qualify if:

• History of previous knee trauma or surgery.
• Physical therapy, intra-articular steroid, or hyaluronic acid injections in the knee within the last 3 months.
• Active oncological diseases.
• Local infection, sepsis, wounds, or scars in the injection area.
• Systemic infections, hepatitis, or immunosuppression.
• Bleeding diathesis or irregular International Normalized Ratio (INR) due to oral warfarin use.
• Inflammatory arthropathies.
• Uncontrolled hypertension, uncontrolled diabetes mellitus, decompensated heart failure, coronary artery disease, or asthma.
• Suspected or confirmed pregnancy.
• Use of corticosteroids or opioids.
• Anemia.
• Body mass index (BMI) greater than 35.
• Allergy to citrate.
• Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within the last week that may affect platelet function analyzer-100 (PFA-100) activity.
• Physical examination findings suggestive of patellar retinaculum, meniscus, or cruciate ligament injury.

Sponsors & Collaborators

• Ankara City Hospital Bilkent: lead

Study Sites (1)

Ankara Bilkent City Hospital, Physical Therapy and Rehabilitation Hospital

Ankara, Çankaya, 06800, Turkey (Türkiye)

RECRUITING

Related Publications (7)

• Shen L, Yuan T, Chen S, Xie X, Zhang C. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res. 2017 Jan 23;12(1):16. doi: 10.1186/s13018-017-0521-3.

  PMID: 28115016 BACKGROUND

• Sit RWS, Wu RWK, Law SW, Zhang DD, Yip BHK, Ip AKK, Rabago D, Reeves KD, Wong SYS. Intra-articular and extra-articular platelet-rich plasma injections for knee osteoarthritis: A 26-week, single-arm, pilot feasibility study. Knee. 2019 Oct;26(5):1032-1040. doi: 10.1016/j.knee.2019.06.018. Epub 2019 Jul 30.

  PMID: 31375446 BACKGROUND

• Tao X, Aw AAL, Leeu JJ, Bin Abd Razak HR. Three Doses of Platelet-Rich Plasma Therapy Are More Effective Than One Dose of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis. Arthroscopy. 2023 Dec;39(12):2568-2576.e2. doi: 10.1016/j.arthro.2023.05.018. Epub 2023 May 24.

  PMID: 37236291 BACKGROUND

• Mascarenhas R, Saltzman BM, Fortier LA, Cole BJ. Role of platelet-rich plasma in articular cartilage injury and disease. J Knee Surg. 2015 Feb;28(1):3-10. doi: 10.1055/s-0034-1384672. Epub 2014 Jul 28.

  PMID: 25068847 BACKGROUND

• Aras B, Celik R, Tezen O, Adiguzel E. Associations of medial collateral ligament and cartilage thickness with clinical outcomes in medial knee osteoarthritis: a cross-sectional study. Clin Rheumatol. 2026 Jan;45(1):441-447. doi: 10.1007/s10067-025-07809-x. Epub 2025 Nov 17.

  PMID: 41247668 BACKGROUND

• Pane RV, Setiyaningsih R, Widodo G, Al Hajiri AZZ, Salsabil JR. Femoral Cartilage Thickness in Knee Osteoarthritis Patients and Healthy Adults: An Ultrasound Measurement Comparison. ScientificWorldJournal. 2023 Feb 17;2023:3942802. doi: 10.1155/2023/3942802. eCollection 2023.

  PMID: 36845755 BACKGROUND

• Testa G, Giardina SMC, Culmone A, Vescio A, Turchetta M, Cannavo S, Pavone V. Intra-Articular Injections in Knee Osteoarthritis: A Review of Literature. J Funct Morphol Kinesiol. 2021 Feb 3;6(1):15. doi: 10.3390/jfmk6010015.

  PMID: 33546408 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Conservative Treatment

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Emre ADIGÜZEL, Prof. Dr.

  Ankara Bilkent City Hospital Physical Therapy and Rehabilitation Hospital

  STUDY DIRECTOR

Central Study Contacts

Rıdvan E ÇELİK

CONTACT

+905078414386; ridvancelik94@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Model Details: This randomized, parallel-group study will compare the effects of conservative treatment alone, intra-articular platelet-rich plasma (PRP) injections in addition to conservative treatment, and combined intra-articular and peri-articular PRP injections in patients with chronic knee osteoarthritis (OA). Participants will be assigned to one of three intervention groups. Clinical and ultrasonographic outcomes will be assessed at baseline, 1 week after completion of treatment, and 3 months after completion of treatment.

Study Record Dates

• First Submitted: January 2, 2026
• First Posted: January 14, 2026
• Study Start: August 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: April 30, 2026
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)