PRP-HA Versus HA in Knee Osteoarthritis

Randomized Controlled Trial Comparing Cellular Matrix Combination of Platelet Rich Plasma With Hyaluronic Acid (CM-PRP-HA) Versus Hyaluronic Acid in Knee Osteoarthritis

Osteoarthritis (OA) is a prevalent chronic condition which most commonly affects the knee. The pathogenesis of OA involves initial mechanical stress resulting in cartilage lesions, leading to inflammatory processes causing joint degradation. Numerous pharmacological and non-pharmacological therapies have been employed, including hyaluronic acid (HA) supplementations to alleviate the joint damage from mechanical load by acting as a shock absorber which provides lubrication, and intra-articular corticosteroid injections to reduce inflammation. However, HA is unable to facilitate cartilage regeneration and corticosteroids has numerous undesirable side effects which render them unsustainable treatment options.

Recently, many studies worldwide have demonstrated that platelet-rich-plasma (PRP) stimulates cartilage repair by actively secreting growth factors which activate cell proliferation and differentiation thereby promoting tissue regeneration. However, there has been varying results across various RCTs due to the heterogeneity of studies, with inconclusive recommendations on the treatment regimen for PRP-HA. Currently, PRP treatment is also not formally recognized as a treatment modality for knee OA in many countries, including Singapore.

This randomised controlled trial aims to compare the efficacy of Cellular Matrix (CM) PRP-HA versus HA (Synolis VA) intra-articular injections in knee OA through quantifying the improvement in long-term treatment outcomes such as pain, stiffness, and functional impairment, potentially improving the quality of life for many patients with knee OA.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Biological: Hyaluronic acid (Synolis VA); Biological: Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA)

Detailed Description

In vitro experimentations have also established the efficacy of PRP, where chondrocytes stimulated with PRP has shown to increase proteoglycan and collagen synthesis which bears similar biochemical qualities to that of hyaline cartilage. PRP has also shown to provide more critical growth factors (including PDGF, TGF-beta, IGF, EGF, VEGF, FGF) than conventional culture media, increasing the synthesis of major cellular proteins and collagen in the extracellular component of intervertebral disc cells, potentially enhancing the functional properties of joint cartilages.

Presently, cellular matrix (CM) remains as the only device which allows for the combination of PRP and HA to be delivered to patients within a single intra-articular injection. However, there are insufficient large-scale studies to reliably evaluate the efficacy of PRP-HA on knee OA and formulate a universal recommendation on its treatment regimen. There are also no RCTs conducted on our local population to explore the effects of CM-PRP-HA on knee OA.

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Kenon Chua, MBBS, MRCSEd, FRCSEd; Phone Number: +65 6222 3322; Email: kenonchua@icloud.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of age 30 years and above
• Radiographical diagnosis of knee OA - ie narrowing of joint space, presence of osteophytes, possible sclerosis and subchondral cysts
• History of chronic pain in knee or knee swelling for at least 3 months
• Ability of patients to provide informed consent

Exclusion Criteria:

• Concurrent complementary and alternative medicine (CAM) treatments e.g. acupuncture
• Inflammatory diseases / infection / fracture / trauma
• Malignancies
• Pregnant or lactating females
• Consistent use of NSAIDs within 48 hours of procedure
• Corticosteroid injection at treatment site within 1 month
• Systemic use of corticosteroids within 2 weeks
• Tobacco use
• (For patients receiving PRP-HA injection only): Hemoglobin <10 g/dL and platelets <150,000/mm3

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HA; Patients will receive 2 intra-articular injections of 2mL Synolis VA (20 mg/mL HA and 40 mg/mL sorbitol), with an interval of 1 month between both injections.	Biological: Hyaluronic acid (Synolis VA); Synolis VA harbours the following characteristics: NaHA (Sodium hyaluronate): 20mg/mL, biofermantative and pharmaceutical grade origin.; Sorbitol: 40mg/mL; Molecular weight of 2MDa, sterilized in moist heat
Experimental: PRP-HA; Patients will receive 2 intra-articular injections of 5mL CM-PRP-HA combination (3mL of autologous PRP, 2mL of 16mg/mL HA), with an interval of 1 month between both injections.	Biological: Cellular Matrix platelet-rich-plasma with hyaluronic acid (CM PRP-HA); The CM-PRP-HA tube is under vacuum containing the following: 2mL of hyaluronic acid gel in phosphate buffer (Sodium chloride, Dipotassium hydrogenphosphate, Potassium dihydrogenphosphate, Potassium chloride and water for injection). Not crosslinked Hyaluronic Acid (40mg per tube) is obtained from fermentation; 3g of inert cell-selector gel; 0.6mL of anticoagulant (sodium citrate 4%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score	WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes	Baseline
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 1 month	WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes	1 month after last injection
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 3 months	WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes	3 months after last injection
Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline at 6 months	WOMAC score comprises pain score, stiffness score and functional impairment score. Pain scores range from 0 to 20, stiffness scores range from 0 to 8, functional impairment scores range from 0 to 68. Total WOMAC score, which is an addition of the above 3 components, range from 0 to 96. Higher scores indicate worse outcomes	6 months after last injection

Collaborators and Investigators

• Sponsor: Singapore General Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: October 1, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Hyaluronic acid; Platelet-rich plasma
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: in progress (Kaul Pediatric Research Institute of the Alabama Children's Hospital Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Aggregate data will be made available

Drug and device information, study documents

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