Degenerative Joint Disease of Knee, Rheumatoid Arthritis
Conditions
Keywords
Neuroinflammation, Palmitoylethanolamide, Adelmidrol, Hyaluronic Acid, Intra-Articular Injection, Knee Pain, Arthritis, Rheumatoid, Osteoarthritis, Knee
Brief 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 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.
Interventions
DEVICEAdelmidrol 2% / Hyaluronic Acid 1%
Ultrasound-guided intra-articular knee injection, 2 mL per injection, administered once weekly for three weeks.
DIETARY_SUPPLEMENTmicronized Palmitoylethanolamide (mPEA) 300mg + ultramicronized Palmitoylethanolamide (umPEA) 600mg
Oral administration of m-/um-PEA, one sachet twice daily for 6 weeks, followed by 1 sachet daily for 8 weeks.
Sponsors
Universita di Verona
Azienda Ospedaliera Universitaria Integrata Verona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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 * Chronic Non-Steroidal Anti-Inflammatory Drugs (NSAID) therapy * Pregnancy or breastfeeding * Known hypersensitivity to study treatments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in joint symptoms and function | Baseline (T0) and 1 month after treatment (T3) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC score | Baseline (T0), 1 week (T1), 2 weeks (T2), 3 months after treatment (T4) and 6 months after treatment (T5) | 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). |
| Change in pain intensity | Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5) | 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. |
| Change in patients' quality of life | Baseline (T0), 1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5) | 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. |
| Incidence of Treatment-Related Adverse Events (Safety and Tolerability) | From first treatment administration up to 6 months after treatment | Treatment safety is assessed by monitoring the incidence and severity of adverse events immediately after injections and throughout the study. |
| Change in analgesic consumption | Baseline (T0), 1 week (T1), 2 weeks (T2), 1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5) | 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. |
| Change of patients' self-assessed health status | 1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5) | 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). |
Countries
Italy
Contacts
CONTACTEnrico Polati
PRINCIPAL_INVESTIGATOREnrico Polati
Università di Verona, Dipartimento di Scienze Chirurgiche Odontostomatologiche e Materno-Infantili
Outcome results
None listed