Etodolac Nanogel as an Adjunct to Physiotherapy for Knee Osteoarthritis

Effect of Etodolac-Loaded Solid Lipid Nanoparticle Gel as an Adjunct to Physiotherapy in Knee Osteoarthritis: A Randomized Clinical Tria

Brief Summary:

Knee osteoarthritis (OA) is a common, disabling condition affecting the weight-bearing knee joint, leading to pain, reduced function, and muscle weakness, particularly of the quadriceps. Strengthening exercises are recommended to improve joint stability, physical function, and slow disease progression. Etodolac, a selective NSAID approved for osteoarthritis, has proven analgesic and anti-inflammatory effects. This study investigates the adjunctive effect of a topical Etodolac-loaded solid lipid nanoparticle gel combined with traditional physiotherapy in patients with knee OA. Thirty patients with mild to moderate unilateral tibiofemoral OA will be randomized into two groups: traditional physiotherapy alone or physiotherapy plus Etodolac gel. Outcomes including pain, knee function, functional performance, quadriceps strength, and proprioception will be assessed at baseline and after four weeks. The study aims to determine whether adding topical Etodolac enhances the benefits of standard physiotherapy in managing knee OA.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Combination product: Etodolac-Loaded Solid Lipid Nanoparticle Gel

Detailed Description

This randomized clinical trial investigates the effect of adding a topical Etodolac-loaded solid lipid nanoparticle gel to traditional physiotherapy in patients with mild to moderate unilateral knee osteoarthritis (OA). Thirty patients aged 45-60 years will be randomly assigned to either physiotherapy alone (control) or physiotherapy plus Etodolac nanogel (experimental) for 4 weeks. Outcomes include pain (VAS), knee function (WOMAC), functional performance (TUG, 2MWT), quadriceps strength, and proprioception. The study aims to determine whether the combination therapy provides superior pain relief, improved joint function, and enhanced muscle performance compared with physiotherapy alone, while potentially reducing systemic NSAID exposure

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ola elgohary, lecturer; Phone Number: 01227191398; Email: ola.elgohary@pua.edu.eg
• Study Contact Backup: Name: Yosra Elnagar, proffesor; Phone Number: 01277629944; Email: yosra.elnaggar@pua.edu.eg

Study Locations

• Egypt
  • Alexandria, Egypt, 21614
    • Pharos University-Faculty of Physical Therapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age between 45 and 60 years.

Mild to moderate unilateral knee osteoarthritis (Kellgren-Lawrence grades II-III).

Ability to walk independently without assistive devices.

Body Mass Index (BMI) < 30 kg/m².

No participation in resistance training in the 3 months prior to enrollment.

Referred by an orthopedic surgeon and diagnosed based on clinical and radiological examination.

Exclusion Criteria:

• Severe or bilateral knee osteoarthritis (Kellgren-Lawrence grade IV).

Congenital or acquired inflammatory, rheumatic, or neurological disorders affecting the knee.

Repeated treatment with steroids or secondary knee OA.

History of joint replacement surgery in the knee or hip.

Cardiovascular or neuromuscular disorders.

Diabetes mellitus.

Psychiatric disorders.

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
Experimental: Traditional Physiotherapy + Etodolac-Loaded Nanoparticle Gel; Participants will receive the same structured physiotherapy program as the control group, in addition to topical application of Etodolac-loaded solid lipid nanoparticle gel on the affected knee. Physiotherapy components: Quadriceps strengthening exercises Lower limb muscle conditioning Aerobic walking program Functional mobility exercises Etodolac nanogel application: Applied topically according to the study protocol to provide localized analgesic and anti-inflammatory effects. Duration: 4 weeks, with standardized physiotherapy sessions and daily topical gel application. Purpose: To evaluate whether adding Etodolac-loaded nanoparticle gel enhances pain relief, knee function, functional performance, quadriceps strength, and proprioception compared with physiotherapy alone	Combination product: Etodolac-Loaded Solid Lipid Nanoparticle Gel; Physiotherapy program includes: Quadriceps strengthening exercises Lower limb muscle conditioning Aerobic walking program Functional mobility exercises; Other Names: Traditional Aerobic Training
Active Comparator: Traditional Physiotherapy Exercises; Participants will receive a structured physiotherapy program for knee osteoarthritis, which includes: Quadriceps strengthening exercises Lower limb muscle conditioning Aerobic walking program Functional mobility exercises Duration: 4 weeks, following standardized procedures for all participants. Purpose: To serve as the control group for comparison with the experimental group receiving additional Etodolac-loaded nanoparticle gel	Combination product: Etodolac-Loaded Solid Lipid Nanoparticle Gel; Physiotherapy program includes: Quadriceps strengthening exercises Lower limb muscle conditioning Aerobic walking program Functional mobility exercises; Other Names: Traditional Aerobic Training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Severity	Pain severity in patients with knee osteoarthritis measured using the Visual Analog Scale (VAS)Units on a 0-10 scale	Baseline, 4 weeks, 8 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Improvement	Improvement in knee function assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale-Units on a 0-68 scale	Baseline, 4 weeks, 8 weeks
Patient Global Assessment of Disease Activity	Patient's overall assessment of their osteoarthritis symptoms measured using a 0-100 scaleوUnits on a 0-100 scale	Baseline, 4 weeks, 8 weeks
Physician's Global Assessmen	Physician's assessment of the patient's overall osteoarthritis status using a standardized scale-Units on a 0-100 scale	Baseline, 4 weeks, 8 weeks

Collaborators and Investigators

• Sponsor: Pharos University in Alexandria

Publications and helpful links

General Publications

• Trojian, T. H., Concoff, A. L., Joy, S. M., Hatzenbuehler, J. R., Saulsberry, W. J., & Coleman, C. I. (2016). AMSSM scientific statement concerning viscosupplementation injections for knee osteoarthritis: importance for individual patient outcomes. British journal of sports medicine, 50(2), 84-92. 2 Murphy, L., Schwartz, T. A., Helmick, C. G., Renner, J. B., Tudor, G., Koch, G., ... & Jordan, J. M. (2008). Lifetime risk of symptomatic knee osteoarthritis. Arthritis Care & Research, 59(9), 1207-1213. 3 Altman, R., Lim, S., Steen, R. G., & Dasa, V. (2015). Hyaluronic Acid Injections Are Associated with Delay of Total Knee Replacement Surgery in Patients with Knee Osteoarthritis: Evidence from a Large US Health Claims Database. PloS one, 10(12). 4 Jegu AG, Pereira B, Andant N, and Coudeyre E. (2014). Effect of eccentric isokinetic strengthening in the rehabilitation of patients with knee osteoarthritis: Isogo, a randomized trial. Trials; 15(1): 106. 5 Segal, N. A., Williams, G. N., Davis, M. C., Wallace, R. B., & Mikesky, A. E. (2015). Efficacy of Blood Flow-Restricted, Low-Load Resistance Training in Women with Risk Factors for Symptomatic Knee Osteoarthritis. PM&R, 7(4), 376-384

Study record dates

Study Major Dates

• Study Start (Estimated): January 8, 2026
• Primary Completion (Estimated): February 7, 2026
• Study Completion (Estimated): March 7, 2026

Study Registration Dates

• First Submitted: December 7, 2025
• First Submitted That Met QC Criteria: December 19, 2025
• First Posted (Actual): December 29, 2025

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: osteoarthritis-Etodolac
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: PUA-PT-ETO-KOA-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Reason: Data contains sensitive patient information and will be used only for the purposes of this study under confidentiality agreements.

Access: Data may be available upon reasonable request to the principal investigator for approved research purposes, following ethical and institutional approvals

Drug and device information, study documents

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