Study to Investigate the Mechanism of Action of an Oral Enzyme Treatment With Bromelain, Trypsin and Rutoside Versus Placebo in Subjects With OsTeoarthritis

NCT05038410 | Completed

• 1 other identifier: 2020CLI
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the pharmacodynamic profile of an oral enzyme treatment with Bromelain, Trypsin and Rutoside in subjects with osteoarthritis.

Conditions

Osteoarthritis

Outcome Measures

Primary Outcomes (4)

• Effects on cartilage biomarkers

  Change in sera biomarkers sColl2-1, sColl2-1NO2, sCOMP, sPIIANP and urine biomarker uCTXII between visit 0 and visit 5 measured using immunoassays (Enzyme-linked Immunosorbent assay, ELISA)

  20 weeks

• Effects on markers of innate immune response

  Change in the expression of M1/M2 Polarization specific membrane markers on fresh blood macrophage, between visit 0 and visit 5 using flow cytometry

  20 weeks

• Effects on systemic inflammatory markers

  Change in sera biomarkers NLRP 3 Inflammasome, α-2-macroglobulin, IL-1β, TNFα, IL-6, IL-10, IL-4 between visit 0 and visit 5 measured using immunoassays (Enzyme-linked Immunosorbent assay, ELISA)

  20 weeks

• Effects on cellular pathways

  Change in plasma proteomic profile using liquid chromatography-tandem mass spectrometry (LC-MS/MS) between visit 0 and visit 5.

  20 weeks

Secondary Outcomes (19)

• Vital signs and anthropomorphic measurements

  40 weeks

• Vital signs and anthropomorphic measurements

  40 weeks

• Vital signs and anthropomorphic measurements

  40 weeks

• Vital signs and anthropomorphic measurements

  40 weeks

• Knee Pain

  36 weeks

Study Arms (2)

Wobenzym®

ACTIVE COMPARATOR

Medicinal product Wobenzym® containing Bromelain (67.5-76.5 mg) adjusted to 450 FIP units, Trypsin (32-48mg) adjusted to 24 µkat and Rutoside trihydrate (100mg).

Drug: Wobenzym®

PLACEBO

PLACEBO COMPARATOR

No active ingredients. The active ingredients will be substituted by microcrystalline cellulose.

Other: Placebo

Interventions

Wobenzym® DRUG

Wobenzym®

Wobenzym®

Placebo OTHER

Microcrystalline cellulose

PLACEBO

Eligibility Criteria

• Age: 40 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 40 years of age and with BMI ≤ 35 kg/m2;
• Uni- or bilateral femorotibial knee OA :
• Responding to clinical and radiological criteria of American College of Rheumatology (ACR);
• Symptomatic for more than 6 months in the index knee;
• Radiological Kellgren \& Lawrence (K\&L) grade II-III in standing x-rays from less than 12 months.
• Mild-to-Moderate mean knee pain score at rest or at walking over the last 24 hours on the index knee evaluated on VAS (0-100) ≥ 40 at baseline;
• Able to follow the instructions of the study;
• Having signed an informed consent.

You may not qualify if:

• Related to knee:
• Recent macro-trauma of the knee responsible of the symptomatic knee left to the Investigator's discretion;
• Concurrent articular disease interfering with the evaluation of pain left to the Investigator's discretion;
• Prosthesis in the target knee;
• Knee swelling requiring corticosteroids local injection.
• Related to treatments:
• Corticosteroids injection in the target knee in the last 3 months;
• Hyaluronan injection in the target knee in the last 6 months;
• Arthroscopy in the last 6 months;
• Oral corticotherapy ≥ 5mg/day (in Prednisolone equivalent) in the last 3 months;
• Symptomatic slow-acting drugs for osteoarthritis (SYSADOA) or dietary supplement, i.e., curcuma extract, chondroitin, glucosamine, diacerein or avocado-soya unsaponifiables in the last 3 months;
• An anticipated need for any forbidden treatments during the trial;
• Contraindications to the product :
• severe hepatic and renal impairment
• congenital or acquired coagulation disorders, e.g. haemophilia

Sponsors & Collaborators

• Mucos Pharma GmbH & Co. KG: lead
• Société des Produits Nestlé (SPN): collaborator
• Artialis: collaborator

Study Sites (5)

Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim

Antwerp, 2020, Belgium

Location

Centre Hospitalier Universitaire (CHU) Brugmann

Brussels, 1020, Belgium

Location

Cliniques Universitaires Saint Luc UCL

Brussels, 1200, Belgium

Location

UZ Brussel

Jette, 1090, Belgium

Location

Centre Hospitalier Régional de la Citadelle

Liège, 4000, Belgium

Location

Related Publications (1)

• Henrotin Y, Pap T, Lieten S, Badot V, Dubuc JE, Urbin-Choffray D, von Eynatten M, Johansen OE, Rau S, Brabants K. Oral enzyme combination therapy reduces systemic inflammation, urinary CTXII and pain in knee osteoarthritis: a proof-of-mechanism, randomised, crossover, double-blind, placebo-controlled trial. RMD Open. 2025 Aug 12;11(3):e005433. doi: 10.1136/rmdopen-2025-005433.

  PMID: 40803821 DERIVED

MeSH Terms

Conditions

Osteoarthritis

Interventions

Wobenzym

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Valerie Badot

  Centre Hospitalier Universitaire (CHU) Brugmann

  PRINCIPAL INVESTIGATOR

• Didier Urbin-Choffray

  Centre Hospitalier Regional de la Citadelle

  PRINCIPAL INVESTIGATOR

• Karl Brabants

  Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim

  PRINCIPAL INVESTIGATOR

• Jean-Emile Dubuc

  Cliniques Universitaires Saint Luc UCL

  PRINCIPAL INVESTIGATOR

• Siddhartha Lieten

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: September 9, 2021
• Study Start: April 30, 2021
• Primary Completion: October 5, 2022
• Study Completion: October 5, 2022
• Last Updated: November 22, 2024

Record last verified: 2022-10

Locations

BE (5)