Osteoarthritis, Knee
Conditions
Keywords
osteoarthritis, Hyaluronic-acid, injection, safety, feasibility
Brief summary
The goal of this clinical trial is to directly compare two hyaluronic acid injection protocols in adults with knee osteoarthritis: a single intra-articular injection of Innoryos 2.5% (Single-Shot) and a three-week injection series of Innoryos 2.2% (Triple-Shot). The study aims to determine whether the single injection provides comparable safety, pain relief, and improvement in knee function to the triple-injection protocol. The main questions are: * How do the single-shot and triple-shot protocols compare in terms of pain reduction and functional improvement? * How do their safety and tolerability profiles compare? * What medical problems occur with each protocol? Participants (n = 46) will receive either the single 4.8 ml injection or three weekly 2 ml injections. They will attend clinic visits at baseline, Week 6, Week 12, and Week 24 for assessments including WOMAC score, 7-day pain diary, functional and strength tests, and MRI scans of the knee. This single-center, partially blinded, randomized study will provide a direct comparison of the two HA injection protocols, assessing whether the single-shot approach is as safe and effective as the triple-shot regimen, while potentially offering a more convenient, patient-friendly treatment.
Detailed description
Background: Knee osteoarthritis (gonarthrosis) is a prevalent degenerative joint disease characterized by cartilage loss, joint pain, stiffness, and functional impairment, which significantly affects mobility and quality of life. Intra-articular injections of hyaluronic acid (HA) are a well-established conservative therapy to reduce pain, improve function, and potentially delay surgical interventions. Various HA formulations and injection protocols exist, differing in molecular weight, concentration, and dosing schedules. Optimizing treatment in terms of efficacy, safety, patient convenience, and cost-effectiveness remains a key clinical goal. Objective: This study aims to compare the safety, tolerability, and efficacy of a single intra-articular injection of Innoryos 2.5% (Single-Shot) with a standard three-week injection regimen of Innoryos 2.2% (Triple-Shot) in adults with moderate to severe knee osteoarthritis. The primary focus is on safety and pain reduction, with secondary outcomes including functional improvement, leg muscle strength, and structural assessment of the knee joint via MRI. Study Design: This is a single-center, randomized, partially blinded, parallel-group clinical intervention study including 46 participants. Patients are randomized using block randomization stratified by baseline WOMAC total score to ensure balanced distribution of baseline pain and functional impairment. Patients and treating physicians are aware of treatment allocation, while all personnel performing functional tests, MRI assessments, data entry, and statistical analyses are blinded to minimize bias. Participants: Adults aged 40-70 years with radiographically confirmed moderate to severe knee osteoarthritis, experiencing knee pain for at least three months and on at least 50% of days in the prior month. Key exclusion criteria include grade 4 osteoarthritis, non-osteoarthritic knee pain, other rheumatic diseases, recent HA or corticosteroid injections, recent trauma or surgery, coagulopathies, autoimmune disorders, pregnancy or lactation, and contraindications for MRI. Interventions: * Single-Shot Group: One intra-articular injection of Innoryos 2.5% (4.8 ml) * Triple-Shot Group: Three intra-articular injections of Innoryos 2.2% (2 ml each) at weekly intervals Outcomes: The primary outcome is total WOMAC score. Secondary outcomes include WOMAC subscales, VAS pain diary, functional performance, leg muscle strength, MRI-detected structural changes, and safety/tolerability parameters. Assessments: Participants are assessed at baseline, Week 6, Week 12, and Week 24. * WOMAC questionnaire (baseline, Week 6, Week 12, and Week 24): Pain, stiffness, and functional limitation * Pain diary (VAS) (baseline, Week 6, Week 12, and Week 24): Daily for 7 days at each assessment (\ 1 min/day) * Functional and strength tests (baseline, Week 6, Week 12): Chair Stand Test, Timed Up and Go Test, isokinetic leg press (\ 30 min per session) * MRI (baseline, Week 6, Week 12): Baseline and Week 12 for structural assessment (\ 90 min including functional tests) * Safety monitoring: Adverse events, medication use, compliance, drop-outs Significance: This study provides high-quality evidence for the direct comparison of single-shot versus triple-shot HA injection protocols in knee osteoarthritis. By using stratified randomization based on baseline WOMAC total score and blinded assessment of outcomes, the trial ensures unbiased evaluation. Demonstration of comparable safety and efficacy of the single-shot regimen could offer a more convenient, patient-friendly, and potentially safer therapeutic option, optimizing conservative management for patients with knee osteoarthritis. intra-articular injection of Innoryos 2.5% (Single-Shot) with a standard three-week injection regimen of Innoryos 2.2% (Triple-Shot) in adults with moderate to severe knee osteoarthritis. The primary focus is on safety and pain reduction, with secondary outcomes including functional improvement, leg muscle strength, and structural assessment of the knee joint via MRI. Study Design: This is a single-center, randomized, partially blinded, parallel-group clinical intervention study including 46 participants. Patients are randomized using block randomization stratified by baseline WOMAC total score to ensure balanced distribution of baseline pain and functional impairment. Patients and treating physicians are aware of treatment allocation, while all personnel performing functional tests, MRI assessments, data entry, and statistical analyses are blinded to minimize bias. Participants: Adults aged 40-70 years with radiographically confirmed moderate to severe knee osteoarthritis, experiencing knee pain for at least three months and on at least 50% of days in the prior month. Key exclusion criteria include grade 4 osteoarthritis, non-osteoarthritic knee pain, other rheumatic diseases, recent HA or corticosteroid injections, recent trauma or surgery, coagulopathies, autoimmune disorders, pregnancy or lactation, and contraindications for MRI.
Interventions
DRUGThree intra-articular hyaluronic acid (HA) injections
Therapy with intra-articular injections of hyaluronic acid (HA). Three intra-articular injections of Innoryos 2.2% (2 ml per injection) administered into the affected knee joint at weekly intervals.
DRUGOne intra-articular hyaluronic acid (HA) injection
Therapy with a single intra-articular injection of hyaluronic acid (HA). One intra-articular injection of Innoryos 2.5% (4.8 ml per injection) administered into the affected knee joint at weekly intervals.
Sponsors
University of Erlangen-Nürnberg Medical School
Friedrich-Alexander-Universität Erlangen-Nürnberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 40-70 years * Radiographically confirmed moderate to severe knee osteoarthritis * Knee pain for ≥3 months * Pain on ≥50% of days in past 30 days * Able to provide informed consent
Exclusion criteria
* Grade 4 osteoarthritis (full-thickness cartilage loss) * Non-osteoarthritic knee pain * Other rheumatic diseases (e.g., rheumatoid arthritis, fibromyalgia) * HA injection \<6 months or corticosteroid injection \<3 months in target knee * Recent trauma or surgery of affected knee (\<6 months) * Coagulopathy or bleeding disorder * Autoimmune or relevant systemic disease * Dermatologic infection at injection site * Pregnancy or lactation * Opioid or oral corticosteroid use * Contraindications to MRI (pacemaker, intracorporeal metal, claustrophobia) * Expected absence during study period or noncompliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC questionnaire total score | At baseline, at 6 weeks, at 12 weeks, at 24 weeks | Total score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), assessing overall pain, stiffness, and physical function of the knee joint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC questionnaire pain subscore | At baseline, at 6 weeks, at 12 weeks, at 24 weeks | Pain subscore of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), assessing pain of the knee joint |
| WOMAC questionnaire stiffness subscore | At baseline, at 6 weeks, at 12 weeks, at 24 weeks | Stiffness subscore of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), assessing stiffness of the knee joint |
| WOMAC questionnaire physical function subscore | At baseline, at 6 weeks, at 12 weeks, at 24 weeks | Physical function subscore of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), assessing pain of the knee joint |
| 7-day pain assessment using visual analog scale (VAS) | At baseline, at 6 weeks, at 12 weeks, at 24 weeks | Participants will record their knee pain daily using a Visual Analog Scale (VAS) as part of a 7-day pain diary at each assessment period. The VAS is a straight 100 mm line, anchored by "no pain" at 0 mm and "worst imaginable pain" at 100 mm. Participants indicate their current knee pain intensity each day by marking a point on the line that best represents their pain. The diary is completed for seven consecutive days to capture fluctuations in pain intensity during daily activities. The daily VAS scores are recorded and later averaged to calculate a weekly mean pain score. |
| Maximum isokinetic leg extension strength | At baseline, at 6 weeks, at 12 weeks, at 24 weeks | Participants' leg muscle strength and functional performance are assessed using an isokinetic leg press (Physiomed, Laipersdorf, Germany). Before testing, participants complete a 5-minute warm-up on a cross-trainer to prepare the muscles and reduce injury risk. Following the warm-up, two maximal test sessions are conducted, each consisting of 6 repetitions at a velocity of 0.6 meters per second (m/s). During each attempt, participants perform the leg press extension movement with maximal effort. The highest peak force achieved during the extension in each session is recorded and used for analysis. |
| 30-Second Chair Stand Test (30s CST) - Assessment of Lower Limb Function: | At baseline, at 6 weeks, at 12 weeks, at 24 weeks | The 30-Second Chair Stand Test measures lower body strength, endurance, and functional mobility. Participants sit on a standard chair with arms crossed over the chest. When instructed, they stand up fully and sit back down repeatedly for 30 seconds. The total number of full stands completed within 30 seconds is recorded. A higher number of repetitions indicates better lower limb strength and functional performance. |
| Knee MRI and T2 Mapping - Assessment of Joint Structures | At baseline, at 12 weeks, at 24 weeks | Magnetic Resonance Imaging (MRI) is used to assess structural changes in the knee joint and evaluate the integrity of cartilage and other joint tissues. Participants undergo a non-invasive, radiation-free MRI scan of the affected knee at baseline and 12 weeks after treatment. The MRI protocol includes high-resolution imaging of joint structures, such as cartilage, menisci, ligaments, and subchondral bone. Additionally, T2 mapping is performed to quantify the T2 relaxation time of articular cartilage, which reflects the water content and collagen organization. Areas of increased T2 values indicate cartilage degeneration or changes in cartilage composition, while decreases or stabilization suggest maintenance or improvement of cartilage health. |
Countries
Germany
Contacts
PRINCIPAL_INVESTIGATORSimon von Stengel, PhD
Institute of Radiology, University Hospital Erlangen, Germany
Outcome results
None listed