The Synergistic Effects of Intra-articular Hyaluronic Acid and Platelet-rich Plasma Injections on Knee Osteoarthritis (HAPRP)

Although intra-articular knee injection with platelet-rich plasma (PRP) may have better outcomes than using hyaluronic acid (HA) for people with knee osteoarthritis (OA), it is expensive to use PRP. Programs with a combination of PRP and HA (PRP+HA) showed good results in vitro and animal studies. This 2-year study aims to clarify the short- and long-term effectiveness of the PRP+HA program for knee OA.

The study will recruit 60 persons aged between 50 and 80 years who have experienced symptomatic knee OA for 6 months or more and have a radiographic picture of knee OA of grades 1-3, based on the Kellegren-Lawrence scale. Those who have diabetes, fever, anemia (Hb <10 g/dl), thrombocytopenia (platelet count <150000/ml), a blood-clotting disease, knee deformity (genu valgum/varum >20 degrees), impaired leg mobility secondary to neuromuscular diseases or a bony fracture, impaired mental function, severe cardiopulmonary impairment, taking anticoagulants long-term, a history of intra-articular steroid injection in the prior 1 year, a history of knee injury involving ligaments and menisci, and a history of malignancy are excluded.

All participants will be randomly divided into group A and group B. At the beginning of the study (T0), group A will receive one course of PRP+HA program and group B will receive one HA course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3 HA injections and a single PRP injection (Arthrex double syringe system). In the 6th month, alternately, group B will receive one PRP+HA program and group A will receive one HA course. The study has 3 outcome assessment tools including a self-administered Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, measurement of quadriceps strength with a digital handheld dynamometer, and measurement of femoral condylar cartilage thickness with musculoskeletal ultrasound. The investigators will conduct those assessments in the beginning (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), and 9th (T4) months.

In the 18th month following the beginning of the study, both groups will receive a booster course of PRP+HA program. During the first week of the program, group A will receive a HA injection before the PRP injection and group B will receive the HA injection after the PRP injection. The investigators will conduct the long-term assessments in the 12th (T5), 15th (T6), 18th (T7), and 21st (T8) months since the beginning of the study.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis Knees Both
• Intervention / Treatment: Combination product: A platelet-rich plasma (PRP)+ hyaluronic acid (HA) program

Detailed Description

People aged >65 years are over 14% in Taiwan since the year 2018. Knee osteoarthritis (OA) is prevalent among elderly people. People with knee OA often have knee pain and stiffness as well as compromised their walking performance and quality of daily life. Although intra-articular knee injection with platelet-rich plasma (PRP) may have better outcomes than using hyaluronic acid (HA), it is expensive to use PRP. Programs with a combination of PRP and HA (PRP+HA) showed good results in vitro and animal studies. This 2-year study aims to clarify the short- and long-term effectiveness of the PRP+HA program for knee OA. The study will also assess the effectiveness of a booster course of PRP+HA program in the second year.

The study will recruit 60 persons aged between 50 and 80 years who have experienced symptomatic knee OA for 6 months or more and have a radiographic picture of knee OA of grades 1-3, based on the Kellegren-Lawrence scale. Those who have diabetes, fever, anemia (Hb <10 g/dl), thrombocytopenia (platelet count <150000/ml), a blood-clotting disease, knee deformity (genu valgum/varum >20 degrees), impaired leg mobility secondary to neuromuscular diseases or a bony fracture, impaired mental function who have difficulty in completing outcome assessments, severe cardiopulmonary impairment, taking anticoagulants long-term, a history of intra-articular steroid injection in the prior 1 year, a history of knee injury involving ligaments and menisci, and a history of malignancy are excluded.

All participants will be randomly divided into group A and group B. At the beginning of the study (T0), group A will receive one course of PRP+HA program and group B will receive one HA course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3 HA injections and a single PRP injection (Arthrex double syringe system). In the 6th month, alternately, group B will receive one PRP+HA program and group A will receive one HA course. The study has 3 outcome assessment tools including a self-administered Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, measurement of quadriceps strength with a digital handheld dynamometer, and measurement of femoral condylar cartilage thickness with musculoskeletal ultrasound. The investigators will conduct those assessments in the beginning (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), and 9th (T4) months.

In the 18th month following the beginning of the study, both groups will receive a booster course of PRP+HA program. During the first week of the program, group A will receive a HA injection before the PRP injection and group B will receive the HA injection after the PRP injection. The investigators will conduct the long-term assessments in the 12th (T5), 15th (T6), 18th (T7), and 21st (T8) months since the beginning of the study.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The study will recruit persons aged between 50 and 80 years who have experienced symptomatic knee OA for 6 months or more. They have a radiographic picture of knee OA of grades 1-3, based on the Kellegren-Lawrence scale.

Exclusion Criteria:

• Those who have diabetes, fever, anemia (Hb <10 g/dl), thrombocytopenia (platelet count <150000/ml), a blood-clotting disease, knee deformity (genu valgum/varum >20 degrees), impaired leg mobility secondary to neuromuscular diseases or a bony fracture, impaired mental function who have difficulty in completing outcome assessments, severe cardiopulmonary impairment, taking anticoagulants long-term, a history of intra-articular steroid injection in the prior 1 year, a history of knee injury involving ligaments and menisci, and a history of malignancy are excluded.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; At the beginning of the study (T0), group A will receive one course of PRP+HA program and group B will receive one HA course (a single HA injection (Hyajoint) weekly for 3 weeks). The PRP+HA program includes 3 HA injections and a single PRP injection (Arthrex double syringe system).	Combination product: A platelet-rich plasma (PRP)+ hyaluronic acid (HA) program; a combination of intra-articular knee injection with platelet-rich plasma (PRP) and hyaluronic acid (HA); Other Names: A hyaluronic acid (HA) course (a single HA injection (Hyajoint) weekly for 3 weeks)
Active Comparator: Group B; In the 6th month, alternately, group B will receive one PRP+HA program and group A will receive one HA course.	Combination product: A platelet-rich plasma (PRP)+ hyaluronic acid (HA) program; a combination of intra-articular knee injection with platelet-rich plasma (PRP) and hyaluronic acid (HA); Other Names: A hyaluronic acid (HA) course (a single HA injection (Hyajoint) weekly for 3 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in WOMAC index	a self-administered Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index	in the beginning (T0) of the study and the following 1st (T1), 3rd (T2), 6th (T3), 9th (T4), 12th (T5), 15th (T6), 18th (T7), and 21st (T8) months.
changes in quadriceps strength	measurement of quadriceps strength with a digital handheld dynamometer	in the beginning (T0) of the study and the following 1st (T1), 6th (T3), 12th (T5), 18th (T7), and 21st (T8) months.
changes in cartilage thickness	measurement of femoral condylar cartilage thickness with musculoskeletal ultrasound	in the beginning (T0) of the study and the following 1st (T1), 6th (T3), 12th (T5), 18th (T7), and 21st (T8) months.

Collaborators and Investigators

• Sponsor: Taipei Medical University WanFang Hospital
• Investigators: Principal Investigator: Kwang-Hwa Chang, MD, Prof.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 22, 2020
• First Posted (Actual): June 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 23, 2020
• Last Update Submitted That Met QC Criteria: June 22, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• 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: N202002101

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: Yes
• product manufactured in and exported from the U.S.: Yes