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

Mucos Pharma GmbH & Co. KG40 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Osteoarthritis

Interventions

Wobenzym®DRUG

Wobenzym®

PlaceboOTHER

Microcrystalline cellulose

Eligibility

Sex: ALLMin age: 40 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Locations (5)

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

Outcomes

Primary Outcomes

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)

Time frame: 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

Time frame: 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)

Time frame: 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.

Time frame: 20 weeks

Secondary Outcomes

Vital signs and anthropomorphic measurements

Changes in systolic and diastolic Blood pressure (BP) in mmHg between visit -1 and visit 6

Time frame: 40 weeks

Vital signs and anthropomorphic measurements

Changes in Heart Rate (HR) measured in beats per minute between visit -1 and visit 6

Time frame: 40 weeks

Vital signs and anthropomorphic measurements

Changes in Temperature measured in degrees Celsius between visit -1 and visit 6

Data from ClinicalTrials.gov

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