Mulligan’s mobilisation with movement and topical diclofenac, alone or in combination, for the management of knee osteoarthritis: a randomised controlled clinical trial
| ISRCTN | ISRCTN11296490 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11296490 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | Protocol No. 10098/11-03-2021 (University General Hospital of Alexandroupolis Scientific Council approval) |
| Sponsor | Democritus University of Thrace |
| Funder | Investigator initiated and funded |
- Submission date
- 27/10/2025
- Registration date
- 17/11/2025
- Last edited
- 17/11/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Knee osteoarthritis is a common condition that causes pain, stiffness, and difficulty moving, which can make everyday activities harder and affect quality of life. Exercise is known to help and is usually the first treatment recommended. Other treatments, like a hands-on technique called the Mulligan Concept and anti-inflammatory gels such as diclofenac (Pennsaid), are also used to ease pain and improve movement.
This study looked at whether combining all three treatments—exercise, Mulligan’s technique, and diclofenac gel—would work better than using just one or two of them.
Who can participate?
Adults (45 - 75 years) diagnosed with knee osteoarthritis were invited to take part in the study.
What does the study involve?
Participants were randomly placed into one of four groups:
-One group did exercise only
-One group did exercise and received Mulligan’s technique
-One group did exercise and used diclofenac gel
-One group did all three: exercise, Mulligan’s technique, and diclofenac gel
They were assessed before treatment, two days after starting, and again at three and six months. Researchers measured pain levels, how well the knee could move, muscle strength, and overall quality of life.
What are the possible benefits and risks of participating?
Participants may experience reduced pain, better movement, and improved quality of life. Risks are expected to be low, but some people may experience mild side effects from the gel or temporary discomfort from the manual therapy.
Where is the study run from?
Democritus University of Thrace (Greece)
When is the study starting and how long is it expected to run for?
December 2020 to March 2025
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Eleni Varsamidou, elenabarsamidou@gmail.com
Contact information
Public, Scientific, Principal investigator
Sintagmatos Kriton 5-7
Komotini
69100
Greece
 ORCID ID |
0009-0009-9446-4546 |
|---|---|
| Phone | +30 6936850210 |
| elvarsam@med.duth.gr |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional prospective randomized controlled four-arm parallel group trial |
| Secondary study design | Randomised parallel trial |
| Scientific title | A prospective, randomized, controlled clinical study investigating the comparative and combined effects of Mulligan’s Mobilisation with Movement (MWM), topical diclofenac (Pennsaid), and their combination, alongside a standardized therapeutic exercise program, on pain, function, and quality of life in patients with knee osteoarthritis. |
| Study acronym | KOA–MWM–NSAID |
| Study objectives | The combined application of Mulligan’s MWM technique and topical diclofenac (Pennsaid), performed in addition to a standardized therapeutic exercise program, will produce superior improvements in pain, range of motion, muscle strength, and quality of life compared with either intervention alone or exercise only in patients with mild-to-moderate knee osteoarthritis. |
| Ethics approval(s) |
Approved 26/03/2021, Scientific Council of the University General Hospital of Alexandroupolis, Greece (6th km Alexandroupolis- Makris, Dragana, Alexandroupoli, 68100, Greece; +30 2551030921; secr@med.duth.gr), ref: Protocol No. 10098/11-03-2021 |
| Health condition(s) or problem(s) studied | Osteoarthritis of the knee |
| Intervention | Randomisation was conducted using sealed, opaque, sequentially numbered envelopes. The allocation sequence was generated by an independent researcher with no involvement in participant assessment or treatment. Block randomisation was applied to ensure balanced allocation across the four groups. Group 1 (Control): Standardised therapeutic exercise programme only (strengthening, stretching, ROM and functional activities), based on EULAR, OARSI, APTA and NICE guidelines. Group 2 (MWM): Mulligan’s Mobilisation with Movement (pain-free tibiofemoral glides combined with active motion) + same exercise programme. 10 sessions (30 min), 3 sessions per week for 4 weeks. Group 3 (Topical NSAID): Topical diclofenac solution (Pennsaid) applied to the affected knee (40 drops, four times daily for 28 days) + same exercise programme. Group 4 (Combined): Mulligan’s MWM + topical diclofenac (Pennsaid) + same exercise programme. |
| Intervention type | Other |
| Primary outcome measure(s) |
Pain intensity (Visual Analogue Scale, VAS) at baseline, 2 days post-intervention, 3 months, and 6 months |
| Key secondary outcome measure(s) |
1. Range of motion (digital goniometer) at baseline, 2 days post-intervention, 3 months, and 6 months |
| Completion date | 03/09/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 45 Years |
| Upper age limit | 75 Years |
| Sex | All |
| Target sample size at registration | 180 |
| Total final enrolment | 250 |
| Key inclusion criteria | 1. Diagnosed primary knee osteoarthritis (ARA/ACR criteria) 2. Kellgren–Lawrence grade ≤ 3 3. Independent ambulation (with/without aids) 4. Written informed consent |
| Key exclusion criteria | 1. Knee pain due to neoplasm or spine pathology 2. Psychiatric or neurological disorders 3. History of lower limb or spinal surgery 4. Intra-articular corticosteroid or hyaluronic acid injections within 6 months 5. Use of systemic corticosteroids in past 4 weeks 6. Contraindications to topical NSAIDs or manual therapy |
| Date of first enrolment | 02/04/2021 |
| Date of final enrolment | 03/03/2025 |
Locations
Countries of recruitment
- Greece
Study participating centre
Alexandroupolis
68100
Greece
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 17/11/2025 | No | No | ||
| Statistical Analysis Plan | 17/11/2025 | No | No |
Additional files
- 48294 Statistical Analysis Plan.pdf
- Statistical Analysis Plan
- 48294 SPIRIT_FULL_PROTOCOL.pdf
- Protocol file
Editorial Notes
28/10/2025: Trial's existence confirmed by Scientific Council of the University General Hospital of Alexandroupolis, Greece.
