Skip to main content
OpenTrials
Completed

NCT Number: NCT07819955

Comparison of the Pain and Functional Improvement of Combined Extracorporeal Shockwave Therapy With or Without Intra-articular Hyaluronic Acid and Platelet-rich Plasma Injection on Advanced Osteoarthritis of the Knees.

This was a single group, double-blind, randomized clinical trial that enrolled 48 patients with Kellgren-Lawrence grade II to IV osteoarthritis of the knee. Patients were randomly assigned to three groups: Saline + ESWT (S+E group), High Platelet-Rich Plasma (PRP + ESWT (P+E group), and Hyaluronic Acid + ESWT (HA + ESWT (H+E group). All patients were followed for one year. Assessments included the Visual Analogue Scale (VAS), serum enzyme-linked immunosorbent assay (ELISA), knee X-ray and ultrasound examinations, and functional scores (WOMAC, KOOS, and IKDC).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Osteoarthritis (OA) Arthritis Joint Diseases Musculoskeletal Diseases Osteoarthritis Rheumatic Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Kaohsiung, 833401, Taiwan

About this study

This is a double-blind trial. The first year's work primarily involves patient enrollment, treatment, and evaluation. We anticipate enrollment will take one year; therefore, patients meeting the inclusion criteria will be gradually enrolled during the first year. Upon enrollment, each patient will undergo blood tests, functional assessments, X-rays, and ultrasound examinations as pre-treatment data. After treatment (depending on their assigned group), functional assessments will be performed every three months, and X-rays and ultrasound examinations will be conducted six months later. The entire treatment period for each patient is one year (6 months of treatment + 6 months of follow-up).

Extracorporeal shock wave therapy (ESWT) is a single high-amplitude sound wave generated by a high-voltage capacitor spark discharge explosion and then focused on the area we want to treat through an elliptical reflector.

Hyaluronic acid is a long-chain polymer composed of disaccharide molecules of D-glucuronic acid and N-acetylglucosamine. It is a major component of the extracellular matrix and is widely present in human body fluids and tissues, including the vitreous humor of the eye and synovial fluid of joints. During osteoarthritis, the concentration and molecular weight of endogenous hyaluronic acid decrease significantly, leading to a decline in its effectiveness in lubricating joints and dispersing intra-articular pressure . Exogenous hyaluronic acid supplementation is effective in anti-inflammatory effects, stimulating the regeneration of endogenous hyaluronic acid, and relieving pain. Current literature confirms that intra-articular injection of hyaluronic acid can be considered as a treatment option to relieve osteoarthritis when other conservative treatments are ineffective .

On the other hand, platelet-rich plasma (PRP) is an emerging treatment option for osteoarthritis of the knee (9). PRP is plasma rich in platelets that can be separated from the patient's own blood using centrifugation. Platelets are organelles in the human body that readily obtain growth factors; therefore, high-concentration platelet plasma also contains many growth factors, including platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF). These high concentrations of growth factors can be used to achieve tissue repair and regeneration. Previous literature has also confirmed that PRP can effectively reduce pain and improve function in patients with osteoarthritis. However, the effects of these two treatment methods on cartilage tissue improvement remain inconclusive.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients aged 20 years and older with phase II, III, or IV osteoarthritis of the knee. The phase of osteoarthritis of the knee is defined according to the Kellgren-Lawrence classification; phase II: Only slight narrowing of the joint cavity, with visible bone spurs.

phase III: Numerous bone spurs, significant narrowing of the joint cavity, and subchondral cysts visible in the subchondral bone.

phase IV: Larger and more prominent bone spurs, severe narrowing of the joint cavity, sclerosis of the subchondral bone, and even joint deformities.

Exclusion criteria

  • Pregnant or breastfeeding women.
  • Patients with arrhythmia or those with pacemakers.
  • Patients with tumors.
  • Individuals with coagulation disorders.
  • Patients with chronic renal failure (glomerular filtration rate < 60).
  • Patients with known allergies to hyaluronic acid, or those with infections or skin diseases.

Treatment and study plan

Extracorporeal Shock Wave Therapy

Device

Extracorporeal Shock Wave Therapy (ESWT) is a non-invasive, injection-free, and radiation-free treatment method commonly used to treat musculoskeletal disorders. Compared to conventional instrument-based treatments, it can reach deeper tissues. Shock waves can cause microscopic damage to injured or poorly healed tissues, promoting tissue repair, angiogenesis, and pain relief.

Using a Storz Medical shockwave therapy machine at an energy of 0.25 mJ/mm², 4000 shocks were administered each time, followed by three treatments at two-week intervals.

normal saline

Drug

Physiological saline solution is a mixture of sodium chloride (salt) and water, with a concentration of 0.9%, and its osmotic pressure is equal to that of human body fluids. Because sterile physiological saline solution has a simple composition and its osmotic pressure is similar to that of the human body and it has no pharmacological activity, it is often used as a sham treatment control group.

Hyaluronic Acid (HA)

Drug

Hyaluronic acid (also known as hyaluronic acid) is a biological polysaccharide with high water absorption and viscoelasticity. It is a component of the articular cartilage matrix and one of the main components of joint lubricating fluid. Hyaluronic acid in the joint cavity can help joints move smoothly, cushion impacts, and reduce wear and tear between articular cartilage.

Platelet-Rich Plasma

Biological

PRP therapy mainly involves drawing the patient's own blood, centrifuging it at high speed through a special extraction tube to separate platelets, and then injecting the concentrated platelets into the joint cavity. Utilizing the repair and regeneration capabilities of the growth factors abundant in the platelet vesicles, it repairs the worn-out meniscus cartilage, promotes tissue regeneration, and relieves the pain of degenerative knee osteoarthritis.

Primary outcomes

  1. VAS（Visual Analogue Scale）

    Time frame: Functional assessments were performed at months 0, 3, 6, 9, and 12 of the treatment course.

    VAS（Visual Analogue Scale）：Ask the patient to mark the degree of their pain on a 10 cm line, from "no pain" on the far left to "unbearable pain" on the far right. The "Numerical Rating Scale" uses a numerical concept of 0-10 points to express the degree of pain, from no pain (0 points) to very painful (10 points).

  2. WOMAC(Western Ontario and McMaster Universities Arthritis Index)

    Time frame: Functional assessments were performed at months 0, 3, 6, 9, and 12 of the treatment course.

    WOMAC is a standardized questionnaire specifically designed to assess the symptoms and functional status of osteoarthritis (degenerative joint disease) of the knee and hip. WOMAC contains 24 items, divided into three categories. Pain (5 items): Assess the degree of pain when walking, climbing stairs, lying down, sitting, or standing. Score range: 0 to 20. Stiffness (2 items): Assess the feeling of stiffness in the joints upon waking in the morning and after resting during the day. Score range: 0 to 8. Physical Function (17 items): Assess the difficulty of performing daily activities such as climbing stairs, getting up, bending over, walking, putting on socks, and doing housework. Score range: 0 to 68.The Likert scale was used for scoring：0 for none, 1 for mild, 2 for moderate, 3 for severe, and 4 for very severe. Total score: The sum of the three scores ranges from 0 to 96. A higher score indicates more severe arthritis symptoms and greater functional impairment.

  3. KOOS scale (Knee Injury and Osteoarthritis Outcome Score)

    Time frame: Functional assessments were performed at months 0, 3, 6, 9, and 12 of the treatment course.

    The KOOS scaleis a standardized questionnaire used to assess the subjective symptoms and quality of life of patients with knee injuries and osteoarthritis. KOOS contains 42 items, independently assessing the following five subscales: 1. Pain: Assessing the frequency and severity of knee pain. 2. Other symptoms: Including swelling, clicking, limited extension or flexion, etc. 3. Daily Living Functions : Ease of performing everyday actions such as going down stairs, sitting down, and putting on socks. 4. Sport/Rec: Performance in activities such as running, jumping, kneeling, or squatting.5. Quality of Life : The psychological impact and distress caused by knee condition on daily life. Scoring Method: Each item is scored on a Likert scale from 0 to 4. Score Range: Each of the five categories is calculated independently and converted to a percentage scale from 0 to 100. Score Meaning: 0 represents the worst knee condition, extremely severe; 100 represents no symptoms and excellent knee

  4. IKDC (International Knee Documentation Committee Subjective Knee Form)

    Time frame: Functional assessments were performed at months 0, 3, 6, 9, and 12 of the treatment course.

    IKDC is suitable for patients with various knee joint conditions (such as ligament injuries, meniscus tears, cartilage problems, or osteoarthritis), and is particularly commonly used for sports injuries and post-operative follow-up. It covers three main categories: symptoms (pain, stiffness, swelling, locking, or weakness. Assess three core symptom categories: assess frequency and severity of pain, stiffness, swelling, joint locking, or knee displacement. Assess sports and activities: assess limitations in daily activities (such as climbing stairs, standing up from a chair, squatting) and during movement or jumping. Assess current overall knee function: the patient's rating of their current knee condition compared to before the injury.

    Scoring and Interpretation: Score range: 0 to 100. Meaning: Higher scores indicate better function and fewer symptoms; 100 points indicates no symptoms and no limitations in daily life or sports.

Secondary outcomes

  1. Enzyme-Linked Immunosorbent Assay

    Time frame: Functional assessments were performed at months 0, 6, and 12 of the treatment course.

    The serum levels of inflammatory factors cytokine IL-6, metabolic inflammatory factor Leptin, cartilage factor COMP (cartilage oligometric protein), osteoinhibitory protein DKK-1 (Dickkopf-1), and cartilage-degrading enzyme MMP-3 (Matrix Metalloproteinase-3) were analyzed.

Other outcomes

  1. Ultrasound Assessment: Joint Effusion

    Time frame: Functional assessments are performed at months 0, 6, and 12 of treatment.

    Measurement of joint effusion in the knee joint using ultrasound examination.Unit of Measure:millimeter (mm)

  2. Ultrasound Assessment: Medial Meniscus (MM) Extrusions Width at Full Extension

    Time frame: Functional assessments were performed at months 0, 6, and 12 of the treatment course.

    Measurement of medial meniscus extrusion width at full extension using ultrasound examination.Unit of Measure: millimeter(mm)

  3. Ultrasound Assessment: Medial Meniscus (MM) Extrusion Width at Standing Weight-Bearing

    Time frame: Functional assessments were performed at months 0, 6, and 12 of the treatment course.

    Measurement of medial meniscus extrusion width during standing weight-bearing using ultrasound examination.Unit of Measure: millimeter(mm)

  4. Ultrasound Assessment: Medial Collateral Ligament (MCL) Thickness at Full Extension

    Time frame: Functional assessments were performed at months 0, 6, and 12 of the treatment course.

    Measurement of medial collateral ligament thickness at full extension using ultrasound examination.Unit of Measure: millimeter(mm)

  5. Ultrasound Assessment: Medial Collateral Ligament (MCL) Thickness at Standing Weight-Bearing

    Time frame: Functional assessments were performed at months 0, 6, and 12 of the treatment course.

    Measurement of medial collateral ligament thickness during standing weight-bearing using ultrasound examination.Unit of Measure: millimeter(mm)

  6. Ultrasound Assessment: Doppler Signal at Medial Meniscus (MM) Body

    Time frame: Functional assessments were performed at months 0, 6, and 12 of the treatment course.

    Assessment of vascularization and inflammation via Doppler ultrasound signal at the medial meniscus body.Unit of Measure: ( Semi-quantitative scale, 0-3)

Sponsors and collaborators

Lead sponsor

Chang Gung Memorial Hospital

Other

Registry information

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Sep 15, 2026
Registry last updated
Sep 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.