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

NCT ID: NCT05038410

Last Updated: 2024-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-30
• Study Completion Date: 2022-10-05

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.

Detailed Description

This study is a randomised, placebo controlled, two parallel arms, cross over, and multicentric trial in 40 male and female subjects suffering from osteoarthritis. While is it well established that Wobenzyme is safe and have proven efficacy in painful conditions, inflammation and osteoarthritis, little is known about its clear mechanism of action underlying its clinical efficacy. This study hypothesises that oral enzyme combination therapy with Wobenzyme will lead to systemic pharmacodynamic effects which will be documented by a holistic assessment of the inflammasome, innate immune system, cartilage turnover, systemic inflammatory markers, as well as potential cellular pathways.

Conditions

Osteoarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Wobenzym®

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).

Group Type: ACTIVE_COMPARATOR

Wobenzym®

Intervention Type: DRUG

Wobenzym®

PLACEBO

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Microcrystalline cellulose

Interventions

Wobenzym®

Wobenzym®

Intervention Type: DRUG

Placebo

Microcrystalline cellulose

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Male or female ≥ 40 years of age and with BMI ≤ 35 kg/m2;

2. Uni- or bilateral femorotibial knee OA :

1. Responding to clinical and radiological criteria of American College of Rheumatology (ACR);

2. Symptomatic for more than 6 months in the index knee;

3. Radiological Kellgren & Lawrence (K&L) grade II-III in standing x-rays from less than 12 months.

3. 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;

4. Able to follow the instructions of the study;

5. Having signed an informed consent.

Exclusion Criteria

Related to knee:

1. Recent macro-trauma of the knee responsible of the symptomatic knee left to the Investigator's discretion;

2. Concurrent articular disease interfering with the evaluation of pain left to the Investigator's discretion;

3. Prosthesis in the target knee;

4. Knee swelling requiring corticosteroids local injection.

Related to treatments:

5. Analgesics to manage knee pain 24 hours before inclusion visit;

6. Corticosteroids injection in the target knee in the last 3 months;

7. Hyaluronan injection in the target knee in the last 6 months;

8. Arthroscopy in the last 6 months;

9. Oral corticotherapy ≥ 5mg/day (in Prednisolone equivalent) in the last 3 months;

10. 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;

11. An anticipated need for any forbidden treatments during the trial;

12. Contraindications to the product :

1. severe hepatic and renal impairment

2. congenital or acquired coagulation disorders, e.g. haemophilia

3. severe liver and/or kidney damage

4. hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

13. Hypersensitivity or allergy to the product components, and pineapple;

14. Treatments based on strontium ranelate, bisphosphonates, selective estrogen-receptor modulator (SERM) and parathormone (PTH) in the last 12 months;

15. Treatment based on zoledronate in the last 2 years;

16. Treatment based on denosumab in the last 6 months;

17. Treatment with anticoagulants and/or anti-platelet agents

Related to associated diseases:

18. Any severe, uncontrolled and limiting disease left to the Investigator's discretion;

19. Patient with widespread pain/depression (e.g. fibromyalgia);

20. Lower or upper extremity surgery or fracture in the last 6 months;

21. Anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the target knee;

22. Severe alteration of mobility enabling functional evaluation.

Related to subjects

23. Close collaborators to the investigational team, the study coordinator (ARTIALIS) or to the Sponsor;

24. Currently participating or having participated in another therapeutic clinical trial in the three previous months;

25. Having made a blood donation in the past month;

26. Under guardianship or judicial protection;

27. Pregnancy, breastfeeding, planned conception, or premenopausal women without effective contraception (tablet, patch, ring, diaphragm, implant and intrauterine device, tubal ligation or hysterectomy);

28. Counter-indication to an MRI examination.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Société des Produits Nestlé (SPN)

INDUSTRY

Sponsor Role: collaborator

Artialis

INDUSTRY

Sponsor Role: collaborator

Mucos Pharma GmbH & Co. KG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valerie Badot

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire (CHU) Brugmann

Didier Urbin-Choffray

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Regional de la Citadelle

Karl Brabants

Role: PRINCIPAL_INVESTIGATOR

Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim

Jean-Emile Dubuc

Role: PRINCIPAL_INVESTIGATOR

Cliniques Universitaires Saint Luc UCL

Siddhartha Lieten

Role: PRINCIPAL_INVESTIGATOR

Universitair Ziekenhuis Brussel

Locations

Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim

Antwerp, , Belgium

Centre Hospitalier Universitaire (CHU) Brugmann

Brussels, , Belgium

Cliniques Universitaires Saint Luc UCL

Brussels, , Belgium

UZ Brussel

Jette, , Belgium

Centre Hospitalier Régional de la Citadelle

Liège, , Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 40803821 (View on PubMed)

Other Identifiers

2020CLI

Identifier Type: -

Identifier Source: org_study_id