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NCT Number: NCT07680101

Intra-Articular Adelmidrol 2%/Hyaluronic Acid 1% With or Without m/umPEA, in Knee Pain Due to Joint Degeneration.

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.

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Key information

Conditions

Degenerative Joint Disease of Knee Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Inflammation Joint Diseases Musculoskeletal Diseases Nervous System Diseases Neuroinflammatory Diseases Osteoarthritis Osteoarthritis, Knee Pathologic Processes Pathological Conditions, Signs and Symptoms Rheumatic Diseases Rheumatoid Arthritis Skin and Connective Tissue Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Azienda Ospedaliera Universitaria Integrata Verona

Verona, Italy

Location contact

Enrico Polati

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Adelmidrol 2% / Hyaluronic Acid 1%

Device

Ultrasound-guided intra-articular knee injection, 2 mL per injection, administered once weekly for three weeks.

Other names: Hyadrol®

micronized Palmitoylethanolamide (mPEA) 300mg + ultramicronized Palmitoylethanolamide (umPEA) 600mg

Dietary Supplement

Oral administration of m-/um-PEA, one sachet twice daily for 6 weeks, followed by 1 sachet daily for 8 weeks.

Other names: Normast® MPS

Primary outcomes

  1. Change in joint symptoms and function

    Time frame: 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 outcomes

  1. Change in WOMAC score

    Time frame: 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).

  2. Change in pain intensity

    Time frame: 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.

  3. Change in patients' quality of life

    Time frame: 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.

  4. Incidence of Treatment-Related Adverse Events (Safety and Tolerability)

    Time frame: 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.

  5. Change in analgesic consumption

    Time frame: 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.

  6. Change of patients' self-assessed health status

    Time frame: 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).

Study contacts

Contact information is provided by the study sponsor or research team.

Enrico Polati

CONTACT

[email protected]

+39 045 812 6076

Sponsors and collaborators

Lead sponsor

Universita di Verona

Other

Collaborators

  • Azienda Ospedaliera Universitaria Integrata Verona

Registry information

Official study 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.

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Jul 2, 2026
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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