Degenerative Joint Disease of KneeNCT07680101
Intra-Articular Adelmidrol 2%/Hyaluronic Acid 1% With or Without m/umPEA, in Knee Pain Due to Joint Degeneration.
A study testing Adelmidrol 2% / Hyaluronic Acid 1% and micronized Palmitoylethanolamide (mPEA) 300mg + ultramicronized Palmitoylethanolamide (umPEA) 600mg in people with Degenerative Joint Disease of Knee and Rheumatoid Arthritis, run by Universita di Verona at 1 site in Italy.
Trial summary
Degenerative knee joint diseases are characterized by chronic pain, inflammation, and functional impairment. In these conditions, mast cell density in the synovial membrane is increased, resulting in an excessive release of biological mediators involved in key mechanisms of neuroinflammation and in hyaluronic acid… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Degenerative Joint Disease of Knee, Rheumatoid Arthritis
- What is being tested?
- Adelmidrol 2% / Hyaluronic Acid 1% and micronized Palmitoylethanolamide (mPEA) 300mg + ultramicronized Palmitoylethanolamide (umPEA) 600mg
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2026to Jun 2027
- Phase
- Interventional
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 40 years
- Male or female
- Diagnosis of unilateral or bilateral knee joint degeneration due to osteoarthritis or rheumatoid arthritis, Kellgren-Lawrence grade II-III
- Duration of knee pain ≥ 6 months
- Baseline WOMAC score ≥ 20
- Drug therapy stabilized for at least 3 months in the case of patients with rheumatoid arthritis
- Naïve to palmitoylethanolamide treatment
- Signed informed consent
Who cannot join
- Severe progressive systemic diseases
- Contraindications to intra-articular knee injections
- Intra-articular knee injections within 3 months prior to enrollment
- Knee surgery within 6 months prior to enrollment
- Systemic treatment with chondroprotectors within 1 month prior to enrollment
- Systemic corticosteroid treatment within 1 month prior to enrollment
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- Chronic Non-Steroidal Anti-Inflammatory Drugs (NSAID) therapy
- Pregnancy or breastfeeding
- Known hypersensitivity to study treatments
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Azienda Ospedaliera Universitaria Integrata Verona
Verona
Enrico Polati, enrico.polati@aovr.veneto.it
About this study
Official title: Efficacy of Intra-articular Treatment With Adelmidrol 2% / Hyaluronic Acid 1%, With or Without m/umPEA, in Knee Pain Due to Joint Degeneration: a Bicentric, Prospective, Randomized Study.
Degenerative knee joint diseases are characterized by chronic pain, inflammation, and functional impairment. In these conditions, mast cell density in the synovial membrane is increased, resulting in an excessive release of biological mediators involved in key mechanisms of neuroinflammation and in hyaluronic acid depolymerisation. Adelmidrol acts as a preventive antioxidant due to its radical scavenging activity, thus protecting hyaluronic acid from oxidative degradation and reducing mast cell degranulation. Furthermore, a reduction in endogenous Palmitoylethanolamide (PEA) levels also contributes to joint neuroinflammation and disease progression; therefore, its exogenous supplementation may represent a valuable supportive strategy.
The objective of this clinical investigation is to compare the efficacy of intra-articular adelmidrol/hyaluronic acid treatment alone versus the same intra-articular treatment combined with oral micronized /ultramicronized PEA in patients with knee joint degeneration due to osteoarthritis or rheumatoid arthritis.
- Being tested
- Adelmidrol 2% / Hyaluronic Acid 1%, micronized Palmitoylethanolamide (mPEA) 300mg + ultramicronized Palmitoylethanolamide (umPEA) 600mg
- Keywords
- Neuroinflammation, Palmitoylethanolamide, Adelmidrol, Hyaluronic Acid, Intra-Articular Injection, Knee Pain, Arthritis, Rheumatoid, Osteoarthritis, Knee
- Medical subject headings
- Osteoarthritis, Knee, Arthritis, Rheumatoid, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adelmidrol 2% / Hyaluronic Acid 1%Device
Also called Hyadrol®
Ultrasound-guided intra-articular knee injection, 2 mL per injection, administered once weekly for three weeks.
micronized Palmitoylethanolamide (mPEA) 300mg + ultramicronized Palmitoylethanolamide (umPEA) 600mgDietary supplement
Also called Normast® MPS
Oral administration of m-/um-PEA, one sachet twice daily for 6 weeks, followed by 1 sachet daily for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Group A (Hyadrol®) | Active comparator | Participants receive intra-articular injections of adelmidrol 2% / hyaluronic acid 1% (Hyadrol®) administered once weekly for three consecutive weeks. Receives: Device: Adelmidrol 2% / Hyaluronic Acid 1% |
| Group B (Hyadrol® + m-/um-PEA) | Experimental | Participants receive intra-articular injections of adelmidrol 2% / hyaluronic acid 1% (Hyadrol®) administered once weekly for three consecutive weeks, combined with oral micronized/ultramicronized palmitoylethanolamide (m-/um-PEA) (Normast® MPS), one sachet twice daily for 6 weeks, followed by 1 sachet daily for 8 weeks. Receives: Device: Adelmidrol 2% / Hyaluronic Acid 1%; Dietary Supplement: micronized Palmitoylethanolamide (mPEA) 300mg + ultramicronized Palmitoylethanolamide (umPEA) 600mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in joint symptoms and function
Evaluation of degenerative joint disease symptoms and function assessed by Western Ontario and McMaster Universities (WOMAC) scale, a self-report questionnaire consisting of 24 questions divided in pain (5 items), joint stiffness (2 items) and functional limitations (17 items). Each question has 5 possible answers, evaluated on a Likert scale, from 0 (none) to 4 (extreme):
- pain: score from 0 to 20;
- joint stiffness: score from 0 to 8;
- functional limitations: score from 0 to 68.
The sum of the individual scores results in an overall score from 0 to 96 (96 indicates severe disability).
Measured: Baseline (T0) and 1 month after treatment (T3)
Secondary outcomes (6)
Change in WOMAC score
Evaluation of degenerative joint disease symptoms and function assessed by Western Ontario and McMaster Universities (WOMAC) scale, a self-report questionnaire consisting of 24 questions divided in pain (5 items), joint stiffness (2 items) and functional limitations (17 items).
Measured: Baseline (T0), 1 week (T1), 2 weeks (T2), 3 months after treatment (T4) and 6 months after treatment (T5)
Change in pain intensity
Evaluation of pain intensity assessed by the Visual Analogue Scale (VAS) scored from 0 mm to 100 mm, where 0 indicates 'no pain' and 100 corresponds to 'the worst pain ever possible'. The higher the score, the more severe the pain.
Measured: Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5)
Change in patients' quality of life
Quality of Life evaluated by the 12-Item Short Form Health Survey (SF-12). The SF-12 is a self-reported health questionnaire. The score produces two summary measures: a mental (MCS-12) and a physical component score (PCS-12). The PCS-12 score is derived from the subdimensions of general health, physical functioning, role physical, and bodily pain, while the MCS-12 score is derived from the subdimensions of social functioning, role emotional, mental health, and energy. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.
Measured: Baseline (T0), 1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5)
Incidence of Treatment-Related Adverse Events (Safety and Tolerability)
Treatment safety is assessed by monitoring the incidence and severity of adverse events immediately after injections and throughout the study.
Measured: From first treatment administration up to 6 months after treatment
Change in analgesic consumption
Analgesic consumption is evaluated by the Cumulative Analgesic Consumption Score (CACS), an index that quantifies the overall use of analgesic medications, taking into account the type, dosage, and frequency of the different analgesics administered.
Measured: Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5)
Change of patients' self-assessed health status
The patient's global health status is evaluated through the Likert Patient Global Impression of Change (PGIC) scored in 7 points (from 1, very much improved to 7, very much worse).
Measured: 1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2026
- Study startJun 2026 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Degenerative Joint Disease of KneeStudies 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
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universita di Verona
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliera Universitaria Integrata Verona
- Responsible party
- Sponsor
- Investigators
- Enrico Polati, Principal investigator, Università di Verona, Dipartimento di Scienze Chirurgiche Odontostomatologiche e Materno-Infantili
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07680101
- Sponsor's protocol ID
- KneeGrease
- Status last verified
- Jun 2026
- First submitted
- 25 Jun 2026
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Guida F, Rocco M, Luongo L, Persiani P, Vulpiani MC, Nusca SM, Maione S, Coluzzi F. Targeting Neuroinflammation in Osteoarthritis with Intra-Articular Adelmidrol. Biomolecules. 2022 Oct 11;12(10):1453. doi: 10.3390/biom12101453.
PubMed 36291664