Biological Response to Platelet-rich Plasma and Corticosteroid Injections

Sponsor

University of Missouri-Columbia (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05657496

Collaborator

(none)

Enrollment

Arms

14.6

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis	Drug: Triamcinolone Acetonide 40 mg/ml Inj, Susp Biological: Platelet-rich plasma Inj	Phase 1/Phase 2

Detailed 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:

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.
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).
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The patient is randomized into one of two treatment arms. Randomization is employed using a computer-generated random assignment sequence and results kept in envelopes. The patient is blinded to the injection received. Subjects receive the injection indicated by study arm at initial visit with a synovial fluid aspiration, urine, and blood collection. At the 1-month visit, subjects provide blood, urine, and synovial fluid aspiration. After the 1-month visit if the patient is experiencing pain and wants an injection, they are instructed to schedule a visit with the PI. If an injection is indicated, the patient is unblinded to which injection they previously received and may choose which to receive. If subject received steroid injection at initial visit, they must wait 3 months before receiving another steroid injection per standard of care guidelines. Subjects is required to complete VAS, KOOS-JR, and UCLA activity surveys at baseline, 2, 4, 8, 12, 24 , 26 and 52 weeks.The patient is randomized into one of two treatment arms. Randomization is employed using a computer-generated random assignment sequence and results kept in envelopes. The patient is blinded to the injection received. Subjects receive the injection indicated by study arm at initial visit with a synovial fluid aspiration, urine, and blood collection. At the 1-month visit, subjects provide blood, urine, and synovial fluid aspiration. After the 1-month visit if the patient is experiencing pain and wants an injection, they are instructed to schedule a visit with the PI. If an injection is indicated, the patient is unblinded to which injection they previously received and may choose which to receive. If subject received steroid injection at initial visit, they must wait 3 months before receiving another steroid injection per standard of care guidelines. Subjects is required to complete VAS, KOOS-JR, and UCLA activity surveys at baseline, 2, 4, 8, 12, 24 , 26 and 52 weeks.

Masking:

Single (Participant)

Masking Description:

Syringes will be prepared and masked with opaque tape by the clinic nurses, thus providing blinding for subjects.

Primary Purpose:

Basic Science

Official Title:

Biological Response to Platelet-rich Plasma and Corticosteroid Injections

Anticipated Study Start Date :

Dec 12, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Steroid A 6mL injection at the initial visit of triamcinolone 40 mg/1 mL (Kenalog) with 5 mL of 1% lidocaine	Drug: Triamcinolone Acetonide 40 mg/ml Inj, Susp Prepared in clinic by physician or medical staff Other Names: Corticosteroid injection
Experimental: Platelet-rich Plasma An injection at the initial visit of approximately 4-6 mL of PRP	Biological: Platelet-rich plasma Inj Produced from participant's whole blood venous draw of approximately 15 mL. Prepared by centrifuge in clinical office Other Names: PRP

Arm

Intervention/Treatment

Active Comparator: Steroid

A 6mL injection at the initial visit of triamcinolone 40 mg/1 mL (Kenalog) with 5 mL of 1% lidocaine

Drug: Triamcinolone Acetonide 40 mg/ml Inj, Susp

Prepared in clinic by physician or medical staff

Other Names:

Corticosteroid injection

Experimental: Platelet-rich Plasma

An injection at the initial visit of approximately 4-6 mL of PRP

Biological: Platelet-rich plasma Inj

Produced from participant's whole blood venous draw of approximately 15 mL. Prepared by centrifuge in clinical office

Other Names:

PRP

Outcome Measures

Primary Outcome Measures

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]
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]
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 Outcome Measures

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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
Correlating the change of specific biomarker concentrations with the change of patient-reported outcome scores [12 months]
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 [12 months]
Low of 0, high of 10. Higher score means more pain and worse outcome
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 [12 months]
Low of 0, high of 10. Higher score means better knee function
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 [12 months]
Multiple questions determining knee stiffness, daily functioning with knee involved activities, and knee pain.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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