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

June 25, 2026 updated by: Universita di Verona

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group A (Hyadrol®)
Participants receive intra-articular injections of adelmidrol 2% / hyaluronic acid 1% (Hyadrol®) administered once weekly for three consecutive weeks.
Device: Adelmidrol 2% / Hyaluronic Acid 1%
Ultrasound-guided intra-articular knee injection, 2 mL per injection, administered once weekly for three weeks.
Other Names:
  • Hyadrol®
Experimental: Group B (Hyadrol® + m-/um-PEA)
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.
Device: Adelmidrol 2% / Hyaluronic Acid 1%
Ultrasound-guided intra-articular knee injection, 2 mL per injection, administered once weekly for three weeks.
Other Names:
  • Hyadrol®
Dietary supplement: micronized 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.
Other Names:
  • Normast® MPS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline (T0) and 1 month after treatment (T3)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline (T0), 1 week (T1), 2 weeks (T2), 3 months after treatment (T4) and 6 months after treatment (T5)
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.
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
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.
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)
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.
From first treatment administration up to 6 months after treatment
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.
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
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).
1 month after treatment (T3), 3 months after treatment (T4) and 6 months after treatment (T5)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universita di Verona

Collaborators

Azienda Ospedaliera Universitaria Integrata Verona

Investigators

  • Principal Investigator: Enrico Polati, Università di Verona, Dipartimento di Scienze Chirurgiche Odontostomatologiche e Materno-Infantili

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

June 25, 2026

First Submitted That Met QC Criteria

June 25, 2026

First Posted (Actual)

July 2, 2026

Study Record Updates

Last Update Posted (Actual)

July 2, 2026

Last Update Submitted That Met QC Criteria

June 25, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KneeGrease

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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