Dose-Response Effect of Intra-Articular Ozone in Knee Osteoarthritis

NCT07678996 | Recruiting

• 1 other identifier: Kayseri-GETAT-2025-102
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the clinical efficacy of different doses of intra-articular ozone injections combined with exercise in patients aged 40-75 diagnosed with Grade 2-3 knee osteoarthritis. The main questions it aims to answer are:

• Which intra-articular ozone doses (10 µg/mL, 15 µg/mL, or 20 µg/mL) is most effective in improving pain and physical function in knee osteoarthritis?
• Do combined ozone and exercise therapies provide superior clinical outcomes compared to exercise therapy alone? Researchers will compare four groups (Ozone 10 µg/mL + Exercise, Ozone 15 µg/mL + Exercise, Ozone 20 µg/mL + Exercise and Exercise Alone) to see the dose-dependent effects of ozone therapy. Participants will:
• Complete a structured home exercise program for the duration of the study.
• Receive 3 sessions of intra-articular ozone injections (for patients allocated to the ozone groups).
• Participate follow-up visits for clinical and functional assessments at baseline (before the procedure), immediately after the 3rd injection session, at 1 month after the last ozone injection, and at 3 months after the last ozone injection.

Conditions

Knee Osteoarthritis

Keywords

osteoarthritis; ozone; knee

Outcome Measures

Primary Outcomes (1)

• Numerical Rating Scale at Third Month after the last ozone injection

  The Numerical Rating Scale is an 11-point segment scale used to evaluate the severity of knee joint pain. Scores range from 0 to 10, where 0 indicates "no pain" and 10 indicates "the worst possible pain."

  Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.

Secondary Outcomes (5)

• Knee-specific symptoms and physical function-WOMAC

  Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.

• Osteoarthritis severity and physical disability- Lequesne Algofunctional Index

  Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.

• Overall health-related quality of life- EuroQol 5-Dimension (EQ-5D) questionnaire

  Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.

• 6-Minute Walk Test (6MWT)

  Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.

• Timed Up and Go (TUG) Test

  Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.

Study Arms (4)

10 µg Ozone + Exercise

EXPERIMENTAL

10 mL of ozone injection at a concentration of 10 µg/mL + Home exercise program

Other: ozone injection; Behavioral: Exercise

15 µg Ozone + Exercise

EXPERIMENTAL

10 mL of ozone injection at a concentration of 15 µg/mL + Home exercise program

Other: ozone injection; Behavioral: Exercise

20 µg Ozone + Exercise

EXPERIMENTAL

10 mL of ozone injection at a concentration of 20 µg/mL + Home exercise program

Other: ozone injection; Behavioral: Exercise

Exercise Alone

ACTIVE COMPARATOR

Home exercise program alone

Behavioral: Exercise

Interventions

ozone injection OTHER

All patients allocated to the ozone intervention groups will receive a total of 3 sessions of intra-articular ozone injections, administered once a week for three consecutive weeks. For all three treatment groups, the injection volume will be 10 mL per session, while the ozone concentrations will vary according to the assigned group as Ozone 10 µg/mL + Exercise, Ozone 15 µg/mL + Exercise, and Ozone 20 µg/mL + Exercise.

Also known as: Intra-articular Ozone Injection

10 µg Ozone + Exercise; 15 µg Ozone + Exercise; 20 µg Ozone + Exercise

Exercise BEHAVIORAL

All participants across all four groups will be prescribed a structured home exercise program. This program includes joint range of motion (ROM) exercises; strengthening exercises (including quadriceps strengthening, hamstring strengthening, hip abductor strengthening, and seated calf raises); and flexibility exercises (including hamstring stretching, gastrocnemius-soleus stretching, and quadriceps stretching). The home program will be performed for 30 minutes per day, 5 days a week, throughout the 3-month study period. To improve patient adherence to exercise, patients will be provided with an exercise diary.

10 µg Ozone + Exercise; 15 µg Ozone + Exercise; 20 µg Ozone + Exercise; Exercise Alone

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 40-75 years diagnosed with knee osteoarthritis according to the American College of Rheumatology 2019 criteria
• Grade 2 or 3 knee osteoarthritis based on the Kellgren-Lawrence radiological classification system.
• Presence of chronic knee pain lasting for more than 6 months.
• Numerical Rating Scale score of 3 or higher during knee-loading activities

You may not qualify if:

• Presence or history of acute knee infection, major knee trauma, or inflammatory arthritis
• History of knee fracture or surgical intervention involving the affected knee joint within the last 6 months.
• History of intra-articular injections (e.g., corticosteroids, hyaluronic acid, PRP) into the affected knee joint within the last 6 months.
• History of physical therapy or rehabilitation in the knee region within the last 6 months
• Presence of osteomyelitis adjacent to the knee joint, bacteremia, or hemarthrosis.
• History of malignancy involving the lower extremity.
• Known hypersensitivity or allergy to medical ozone.
• Severe anemia, thrombocytopenia, active bleeding disorders, or ongoing anticoagulant therapy.
• Pregnancy or lactation
• Active infection
• Severe systemic diseases (e.g., advanced cardiopulmonary disease, uncontrolled diabetes mellitus).
• Hyperthyroidism or progressive neuromuscular disorders.
• Cognitive impairment or inability to cooperate with the assessment tools and study protocol.

Sponsors & Collaborators

• Kayseri City Hospital: lead

Study Sites (1)

Kayseri City Hospital

Kayseri, 38080, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Ozone; Exercise

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Oxygen; Gases; Inorganic Chemicals; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Serhat Efdal Ozbek, MD

CONTACT

+905072387257; serhatefdal60@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This study is designed as a single-blind trial. All intra-articular injections will be performed by an physiatrist. All physical and functional assessments (NRS, WOMAC, Lequesne, EQ-5D, 6MWT, and TUG) will be performed by a second, independent physiatrist who is completely blinded to the treatment groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Department of Physical Medicine and Rehabilitation

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: July 1, 2026
• Study Start: November 19, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: July 1, 2026

Record last verified: 2026-06

Locations

TU (1)