Knee OsteoarthritisNCT07678996
Dose-Response Effect of Intra-Articular Ozone in Knee Osteoarthritis
A study testing ozone injection and Exercise in people with Knee Osteoarthritis, run by Kayseri City Hospital at 1 site in Turkey (Türkiye).
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- ozone injection and Exercise
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 19 Nov 2025to 30 Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Kayseri City Hospital
Kayseri, 38080
Serhat Efdal Ozbek, MD, +905072387257, serhatefdal60@gmail.com
Serhat Efdal Ozbek, MD
About this study
Official title: Dose-Response Effect of Intra-Articular Ozone in Knee Osteoarthritis: A Randomized Controlled Single-Blind Clinical Study
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:
Read more
- 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.
Read the detailed description
This clinical trial is designed as a prospective, randomized, controlled study to investigate the dose-dependent therapeutic effects of intra-articular ozone therapy in patients with Grade 2-3 knee osteoarthritis.
Eligible participants aged 40-75 with a confirmed diagnosis of knee osteoarthritis (Kellgren-Lawrence Grade 2 or 3) will be recruited. Participants will be allocated into one of four parallel groups by computerized randomization.
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 at 10 mL per session, while the ozone concentrations will vary according to the assigned group as follows:
Ozone 10 µg + Exercise: 10 mL of ozone injection at a concentration of 10 µg/mL + Home exercise program.
Ozone 15 µg + Exercise: 10 mL of ozone injection at a concentration of 15 µg/mL + Home exercise program.
Ozone 20 µg + Exercise: 10 mL of ozone injection at a concentration of 20 µg/mL + Home exercise program.
Exercise Alone (Control): Home exercise program alone.
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 and flexibility exercises.
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 and also an analgesic diary to track analgesic use.
Clinical and functional evaluations will be performed at four distinct time points: baseline (pre-treatment), immediately after the 3rd injection session (post-treatment), 1 month after the last ozone injection, and 3 months after the last ozone injection. The clinical and functional status of the participants will be evaluated using the Numerical Rating Scale (NRS) for pain severity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for knee-specific symptoms and physical function, the Lequesne Algofunctional Index for osteoarthritis severity and physical disability, and the EuroQol 5-Dimension (EQ-5D) questionnaire for overall health-related quality of life. Additionally, objective functional capacity, dynamic balance, and mobility will be assessed using the 6-Minute Walk Test (6MWT) and the Timed Up and Go (TUG) test.
- Conditions
- Knee Osteoarthritis
- Being tested
- ozone injection, Exercise
- Keywords
- osteoarthritis, ozone, knee
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ozone injectionOther
Also called Intra-articular Ozone Injection
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.
ExerciseBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 10 µg Ozone + Exercise | Experimental | 10 mL of ozone injection at a concentration of 10 µg/mL + Home exercise program Receives: 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 Receives: 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 Receives: Other: ozone injection; Behavioral: Exercise |
| Exercise Alone | Active comparator | Home exercise program alone Receives: Behavioral: Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
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."
Measured: 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
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a self-administered questionnaire specific to knee osteoarthritis, consisting of 24 items divided into 3 subscales: Pain (5 items), Stiffness (2 items), and Physical Function (17 items). Total scores range from 0 to 96, with higher scores indicating worse symptoms and greater physical limitation. Lower scores represent better functional improvement.
Measured: 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
The Lequesne Index is used to assess the severity of knee osteoarthritis and the level of physical disability. It includes questions regarding pain, maximum walking distance, and daily living activities. The total score ranges from 0 to 24. Higher scores indicate more severe osteoarthritis.
Measured: 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
The EQ-5D questionnaire evaluates general health-related quality of life across 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scores are converted into an index score ranging from less than 0 to 1. Higher scores indicate a better quality of life.
Measured: 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)
The 6MWT is an objective clinical test used to assess functional capacity and dynamic mobility. Patients are instructed to walk as far as possible along a straight corridor in 6 minutes. The total distance covered is measured in meters. An increase in the walking distance indicates an improvement in functional mobility.
Measured: 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
The TUG test is used to evaluate dynamic balance, mobility, and fall risk. Patients are timed as they rise from a standard chair, walk 3 meters, turn around, walk back to the chair, and sit down. The outcome is recorded in seconds. Shorter completion times represent better balance and mobility.
Measured: Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2026
- Study start19 Nov 2025
- Primary completion30 Nov 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kayseri City Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Fatma Gül Ülkü Demir, Kayseri City Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07678996
- Sponsor's protocol ID
- Kayseri-GETAT-2025-102
- Status last verified
- Jun 2026
- First submitted
- 16 Jun 2026
- Last updated
- 1 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-Response Effect of Intra-Articular Ozone in Knee Osteoarthritis: A Randomized Controlled Single-Blind Clinical Study
- ClinicalTrials.gov ID
- NCT07678996
- Acronym / sponsor ID
- Kayseri-GETAT-2025-102
- Conditions
- Knee Osteoarthritis
- Keywords
- osteoarthritis, ozone, knee
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Kayseri City HospitalOther government
- Study start
- 19 Nov 2025 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 1 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This clinical trial is designed as a prospective, randomized, controlled study to investigate the dose-dependent therapeutic effects of intra-articular ozone therapy in patients with Grade 2-3 knee osteoarthritis.
Eligible participants aged 40-75 with a confirmed diagnosis of knee osteoarthritis (Kellgren-Lawrence Grade 2 or 3) will be recruited. Participants will be allocated into one of four parallel groups by computerized randomization.
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 at 10 mL per session, while the ozone concentrations will vary according to the assigned group as follows:
Ozone 10 µg + Exercise: 10 mL of ozone injection at a concentration of 10 µg/mL + Home exercise program.
Ozone 15 µg + Exercise: 10 mL of ozone injection at a concentration of 15 µg/mL + Home exercise program.
Ozone 20 µg + Exercise: 10 mL of ozone injection at a concentration of 20 µg/mL + Home exercise program.
Exercise Alone (Control): Home exercise program alone.
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 and flexibility exercises.
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 and also an analgesic diary to track analgesic use.
Clinical and functional evaluations will be performed at four distinct time points: baseline (pre-treatment), immediately after the 3rd injection session (post-treatment), 1 month after the last ozone injection, and 3 months after the last ozone injection. The clinical and functional status of the participants will be evaluated using the Numerical Rating Scale (NRS) for pain severity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for knee-specific symptoms and physical function, the Lequesne Algofunctional Index for osteoarthritis severity and physical disability, and the EuroQol 5-Dimension (EQ-5D) questionnaire for overall health-related quality of life. Additionally, objective functional capacity, dynamic balance, and mobility will be assessed using the 6-Minute Walk Test (6MWT) and the Timed Up and Go (TUG) test.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 10 µg Ozone + Exercise | Experimental | Other: ozone injection, Behavioral: Exercise10 mL of ozone injection at a concentration of 10 µg/mL + Home exercise program |
| 15 µg Ozone + Exercise | Experimental | Other: ozone injection, Behavioral: Exercise10 mL of ozone injection at a concentration of 15 µg/mL + Home exercise program |
| 20 µg Ozone + Exercise | Experimental | Other: ozone injection, Behavioral: Exercise10 mL of ozone injection at a concentration of 20 µg/mL + Home exercise program |
| Exercise Alone | Active comparator | Behavioral: ExerciseHome exercise program alone |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ozone injectionAlso: Intra-articular Ozone InjectionAll 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. | Other | 10 µg Ozone + Exercise, 15 µg Ozone + Exercise, 20 µg Ozone + Exercise |
| ExerciseAll 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. | Behavioural | 10 µg Ozone + Exercise, 15 µg Ozone + Exercise, 20 µg Ozone + Exercise, Exercise Alone |
Primary outcome
Numerical Rating Scale at Third Month after the last ozone injection
Time frame: Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months 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."
5 secondary outcomes
Knee-specific symptoms and physical function-WOMAC
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ozone injection and Exercise in people with Knee Osteoarthritis, run by Kayseri City Hospital at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Serhat Efdal Ozbek, MD (+905072387257, serhatefdal60@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Numerical Rating Scale at Third Month after the last ozone injection (time frame: Baseline, Week 2 (immediately after the 3rd injection session), 1 month after the last ozone injection, and 3 months after the last ozone injection.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.