Biological Response to Platelet-rich Plasma and Corticosteroid Injections

Knee Osteoarthritis Clinical Trial

Official title:

Biological Response to Platelet-rich Plasma and Corticosteroid Injections

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05657496
• Other study ID #: 2092036
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 28, 2022
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: University of Missouri-Columbia
• Contact: James Keeney, MD
• Phone: 573-882-6449
• Email: keeneyj[@]health.missouri.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal is to determine how two different injections, corticosteroid and platelet-rich plasma, are used to treat patients with knee osteoarthritis may affect a patient's pain and function. Secondarily, the investigators are also interested in knowing how the two types of injections that will be given may affect what happens in the joint cartilage. The participants will receive one of the two injection types at the initial visit. There will be surveys to complete (around 10 questions) about the participants' knee and overall function. The investigators will ask these same questions on seven separate occasions. In addition, the investigators will ask the participants to provide blood and urine samples at our clinic before the first knee injection and before any other injection that is needed over the course of the study. During the injections, synovial fluid will be aspirated from the participants' knee at the initial visit and the one month visit. If the participants decide to go to surgery to help relieve the pain from osteoarthritis at any point during the study, the investigators will collect the material from the participants' knee that would be normally discarded as medical waste. Previous studies have indicated that concentrations of inflammatory and degradative biomarkers in patient serum, urine, and synovial fluid may provide insight into OA pathophysiology. To our knowledge, no study has been performed to assess the impact of intra-articular PRP injection upon fluid concentrations of a comprehensive panel of proposed OA-related biomarkers. In this study, the investigators will evaluate the impact of intra-articular PRP injection upon markers of cartilage matrix turnover, inflammatory mediators, degradative enzymes, inhibitors of degradative enzymes, and markers of bone metabolism in serum, urine, and synovial fluid of knee OA patients.

Description:

Knee osteoarthritis (OA) is an extremely common cause of disability, with a global prevalence of 22.9% in adults aged 40 and over. OA is a whole-joint disease characterized by progressive degradation of articular cartilage, chronic inflammation of joint tissue, and subchondral bone remodeling, resulting in severe pain and decreased mobility in patients. No cure currently exists for OA, and treatment is aimed at symptomatic management and prevention of disease progression. Currently, this consists of: 1. Initial conservative treatment for osteoarthritis across all levels of radiographic disease severity includes activity modification, oral analgesic or anti-inflammatory medications, non-supervised or supervised (e.g., physical therapy) exercise, and occasionally bracing. 2. Injection therapies have been used in the treatment of osteoarthritis for more than 60 years. Medical corticosteroids have served as a gold standard for symptom management as an intra-articular injection, but concerns have always existed around the potential for either the steroid medication (which suppresses both repair and inflammation processes) or the local anesthetic co-administered with the steroid to contribute to degradation of joint cartilage over time. Alternative substances have been developed to address the joint environment - with an intent to improve symptoms, while decreasing the potential for joint degeneration. These alternative medications include viscosupplements (hyaluronic acid analogues) and biological agents (platelet-rich plasma, or stem cell therapies). 3. Surgical interventions include arthroscopy for concurrent symptomatic meniscus tears or unstable cartilage that contribute to mechanical symptoms, osteotomy (realignment) surgery for active patients with single compartment arthritis, and arthroplasty (joint replacement) for patients with more limited activity goals, severe arthritis, and temporary-but not sustained---pain relief with the conservative treatments described in #1 and #2. Intra-articular injection of a corticosteroid has been shown to be effective in providing short-term relief of knee OA symptoms, possibly due to anti-inflammatory and immunosuppressive effects. Repeated corticosteroid injections have thus become the standard of care for patients with mild to moderate knee OA. Intra-articular injection of platelet-rich plasma (PRP) has emerged as a promising alternative to corticosteroid injection in knee OA patients. Studies have indicated that PRP is safe and may provide benefits such as pain relief, improved knee function, and enhanced quality of life. Moreover, PRP injection has been shown to provide longer-lasting symptomatic attenuation, with clinically significant improvement observed for as long as 12 months post-injection. Previous studies have indicated that concentrations of inflammatory and degradative biomarkers in patient serum, urine, and synovial fluid may provide insight into OA pathophysiology. To the investigators' knowledge, no study has been performed to assess the impact of intra-articular PRP injection upon fluid concentrations of a comprehensive panel of proposed OA-related biomarkers. In this study, the investigators will evaluate the impact of intra-articular PRP injection upon markers of cartilage matrix turnover, inflammatory mediators, degradative enzymes, inhibitors of degradative enzymes, and markers of bone metabolism in serum, urine, and synovial fluid of knee OA patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Patients aged 40 and over, presenting with a knee disorder of at least one knee
• Patients eligible for use of either corticosteroid or biological agent for treatment of moderate or severe (but not end-stage) knee osteoarthritis
• KL grade of 2-3

Exclusion Criteria:

• Subjects less than 40 years of age
• Previous reconstructive knee surgery
• Participating in another clinical trial
• Unable to receive corticosteroid injections (i.e., allergies, adverse reactions, etc.)
• Unable to sign informed consent
• Pregnant or plan to become pregnant

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis

Intervention

Drug:
• Triamcinolone Acetonide 40 mg/ml Inj, Susp
Prepared in clinic by physician or medical staff

Biological:
• Platelet-rich plasma Inj
Produced from participant's whole blood venous draw of approximately 15 mL. Prepared by centrifuge in clinical office

Locations

Country	Name	City	State
United States	University of Missouri	Columbia	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
University of Missouri-Columbia

Country where clinical trial is conducted

United States, 

References & Publications (9)

Arroll B, Goodyear-Smith F. Corticosteroid injections for osteoarthritis of the knee: meta-analysis. BMJ. 2004 Apr 10;328(7444):869. doi: 10.1136/bmj.38039.573970.7C. Epub 2004 Mar 23. — View Citation

Ayhan E, Kesmezacar H, Akgun I. Intraarticular injections (corticosteroid, hyaluronic acid, platelet rich plasma) for the knee osteoarthritis. World J Orthop. 2014 Jul 18;5(3):351-61. doi: 10.5312/wjo.v5.i3.351. eCollection 2014 Jul 18. — View Citation

Bhatia D, Bejarano T, Novo M. Current interventions in the management of knee osteoarthritis. J Pharm Bioallied Sci. 2013 Jan;5(1):30-8. doi: 10.4103/0975-7406.106561. — View Citation

Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020 Nov 26;29-30:100587. doi: 10.1016/j.eclinm.2020.100587. eCollection 2020 Dec. — View Citation

Filardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A. PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials. Cartilage. 2021 Dec;13(1_suppl):364S-375S. doi: 10.1177/1947603520931170. Epub — View Citation

Lacko M, Harvanova D, Slovinska L, Matuska M, Balog M, Lackova A, Spakova T, Rosocha J. Effect of Intra-Articular Injection of Platelet-Rich Plasma on the Serum Levels of Osteoarthritic Biomarkers in Patients with Unilateral Knee Osteoarthritis. J Clin Me — View Citation

Naal FD, Impellizzeri FM, Leunig M. Which is the best activity rating scale for patients undergoing total joint arthroplasty? Clin Orthop Relat Res. 2009 Apr;467(4):958-65. doi: 10.1007/s11999-008-0358-5. Epub 2008 Jun 28. — View Citation

Nguyen LT, Sharma AR, Chakraborty C, Saibaba B, Ahn ME, Lee SS. Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis. Int J Mol Sci. 2017 Mar 12;18(3):601. doi: 10.3390/ijms18030601. — View Citation

Shamrock AG, Wolf BR, Ortiz SF, Duchman KR, Bollier MJ, Carender CN, Westermann RW. Preoperative Validation of the Patient-Reported Outcomes Measurement Information System in Patients With Articular Cartilage Defects of the Knee. Arthroscopy. 2020 Feb;36( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in concentration of MCP-1 proinflammatory biomarker from baseline in the serum after intraarticular knee injection of PRP at 1 month, 3 months, and 6 months timeframes		12 months
Primary	Difference in concentration of MCP-1 proinflammatory biomarker from baseline in the urine after intraarticular knee injection of PRP at 1 month, 3 months, and 6 months timeframes		12 months
Primary	Difference in concentration of MCP-1 proinflammatory biomarker from baseline in the synovial fluid after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of RANTES proinflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of IL-1b proinflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of IL-6 proinflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of IL-8 proinflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of TNF-a proinflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of MIP-1a proinflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of PGE2 proinflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of IL-1RA anti-inflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of IL-4 anti-inflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of IL-10 anti-inflammatory biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of MMP pro-degradative biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of TIMP-1 anti-degradative biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of TIMP-2 anti-degradative biomarker from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of COMP from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of CTX-1 from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of CTX-II from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of PIICP from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of HA from baseline in the collected specimens after intraarticular knee injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Difference in concentration of biomarkers in the collected specimens after the first intraarticular knee injection of PRP from the second injection of PRP at 1 month, and possibly 3 and 6 months timeframes		12 months
Secondary	Correlating the change of specific biomarker concentrations with the change of patient-reported outcome scores		12 months
Secondary	The change From Baseline in Pain Scores on the Visual Analog Scale at 2 weeks, 4 weeks, 8 weeks, 12 weeks, 6 months, and 12 months	Low of 0, high of 10. Higher score means more pain and worse outcome	12 months
Secondary	The change From Baseline in Scores on the UCLA Activity Score at 2 weeks, 4 weeks, 8 weeks, 12 weeks, 6 months, and 12 months	Low of 0, high of 10. Higher score means better knee function	12 months
Secondary	The change From Baseline in Pain Scores on the Knee Injury and Osteoarthritis Outcome Score-Joint Replacement at 2 weeks, 4 weeks, 8 weeks, 12 weeks, 6 months, and 12 months	Multiple questions determining knee stiffness, daily functioning with knee involved activities, and knee pain.	12 months