Single vs Triple Hyaluronic Acid in Knee Osteoarthritis

NCT07352540 | Not Yet Recruiting Phase 2

• 1 other identifier: 25-275_1-Bm
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Osteoarthritis, Knee

Keywords

osteoarthritis; Hyaluronic-acid; injection; safety; feasibility

Outcome Measures

Primary Outcomes (1)

• WOMAC questionnaire total score

  Total score of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), assessing overall pain, stiffness, and physical function of the knee joint

  At baseline, at 6 weeks, at 12 weeks, at 24 weeks

Secondary Outcomes (7)

• WOMAC questionnaire pain subscore

  At baseline, at 6 weeks, at 12 weeks, at 24 weeks

• WOMAC questionnaire stiffness subscore

  At baseline, at 6 weeks, at 12 weeks, at 24 weeks

• WOMAC questionnaire physical function subscore

  At baseline, at 6 weeks, at 12 weeks, at 24 weeks

• 7-day pain assessment using visual analog scale (VAS)

  At baseline, at 6 weeks, at 12 weeks, at 24 weeks

• Maximum isokinetic leg extension strength

  At baseline, at 6 weeks, at 12 weeks, at 24 weeks

Other Outcomes (3)

• Compliance and Drop-Out

  up to 24 weeks

• Medication Use - Analgesic Tracking

  Up to 24 weeks

• Adverse Effects - Safety Endpoint

  Up to 24 weeks

Study Arms (2)

Three intra-articular HA injections

ACTIVE COMPARATOR

Three intra-articular injections of Innoryos 2.2% (2 ml each) in the knee joint at weekly intervals

Drug: Three intra-articular hyaluronic acid (HA) injections

One intra-articular HA injection

EXPERIMENTAL

One intra-articular injection of Innoryos 2.5% (4.8 ml) in the knee joint

Drug: One intra-articular hyaluronic acid (HA) injection

Interventions

Three intra-articular hyaluronic acid (HA) injections DRUG

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.

Three intra-articular HA injections

One intra-articular hyaluronic acid (HA) injection DRUG

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.

One intra-articular HA injection

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Friedrich-Alexander-Universität Erlangen-Nürnberg: collaborator
• University of Erlangen-Nürnberg Medical School: lead

Related Publications (3)

• Kast S, Kemmler W, Roemer FW, Kohl M, Culvenor AG, Mobasheri A, Uder M, von Stengel S. Effectiveness of whole-body electromyostimulation on knee pain and physical function in knee osteoarthritis: a randomized controlled trial. Sci Rep. 2024 Sep 6;14(1):20804. doi: 10.1038/s41598-024-71552-7.

  PMID: 39242729 BACKGROUND

• Roemer FW, Kast S, Kemmler W, Collins JE, Engelke K, Guermazi A, Uder M, von Stengel S. Structural effects of whole body electromyostimulation on knee osteoarthritis: the EMSOAT Study. Skeletal Radiol. 2025 Nov;54(11):2579-2588. doi: 10.1007/s00256-025-04984-5. Epub 2025 Jul 22.

  PMID: 40694090 BACKGROUND

• Hofweber, L., von Stengel, S., Nürnberger, J., & Kemmler, W. (2024). Effectiveness and safety of the hyaluronic acid INNORYOS 2.2% in patients with early to advanced knee osteoarthritis. A prospective non-interventional randomized clinical trial.

  BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Injections

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Simon von Stengel, PhD

CONTACT

004991318523999; simon.von.stengel@fau.de

Wolfgang Kemmler, PhD

CONTACT

004991318523999; wolfgang.kemmler@fau.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2026
• First Posted: January 20, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share