Clinical trial NCT05038410: Study to Investigate the Mechanism of Action of an Oral Enzyme Treatment With Bromelain, Trypsin and Rutoside Versus Placebo in Subjects With OsTeoarthritis
Official title: Randomized, Double-blind, Placebo-controlled, Crossover Study to Investigate the Mechanism of Action of an Oral Enzyme Treatment With Bromelain, Trypsin and Rutoside Versus Placebo in Subjects With OsTeoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis
Lead sponsor: Mucos Pharma GmbH & Co. KG
Sponsor class: INDUSTRY
Collaborators: name: Société des Produits Nestlé (SPN)
name: Artialis
First posted: 2021-09-09
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Effects on cartilage biomarkers
timeFrame: 20 weeks
measure: Effects on markers of innate immune response
timeFrame: 20 weeks
measure: Effects on systemic inflammatory markers
timeFrame: 20 weeks
measure: Effects on cellular pathways
timeFrame: 20 weeks
Secondary outcomes:
measure: Vital signs and anthropomorphic measurements
timeFrame: 40 weeks
measure: Vital signs and anthropomorphic measurements
timeFrame: 40 weeks
measure: Vital signs and anthropomorphic measurements
timeFrame: 40 weeks
measure: Vital signs and anthropomorphic measurements
timeFrame: 40 weeks
measure: Knee Pain
timeFrame: 36 weeks
measure: Knee Function
timeFrame: 36 weeks
measure: Patient global assessment of disease activity (PGADA)
timeFrame: 36 weeks
measure: Patient physical activity
timeFrame: 36 weeks
measure: Patient physical activity
timeFrame: 36 weeks
measure: Patient physical activity
timeFrame: 36 weeks
measure: Patient physical activity
timeFrame: 36 weeks
measure: Patient physical activity
timeFrame: 36 weeks
measure: Body metabolism
timeFrame: 20 weeks
measure: Clinical chemistry
timeFrame: 20 weeks
measure: Joint structure modification
timeFrame: 36 weeks
measure: Volume of joint effusion
timeFrame: 36 weeks
measure: Tolerance
timeFrame: 40 weeks
measure: Compliance
timeFrame: 36 weeks
measure: Responder rate to treatment
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim
city: Bruxelles
country: Belgium
facility: Centre Hospitalier Universitaire (CHU) Brugmann
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc UCL
city: Jette
country: Belgium
facility: UZ Brussel
city: Liège
country: Belgium
facility: Centre Hospitalier Régional de la Citadelle
Study officials:
affiliation: Centre Hospitalier Universitaire (CHU) Brugmann
name: Valerie Badot
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Regional de la Citadelle
name: Didier Urbin-Choffray
role: PRINCIPAL_INVESTIGATOR
affiliation: Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim
name: Karl Brabants
role: PRINCIPAL_INVESTIGATOR
affiliation: Cliniques Universitaires Saint Luc UCL
name: Jean-Emile Dubuc
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitair Ziekenhuis Brussel
name: Siddhartha Lieten
role: PRINCIPAL_INVESTIGATOR
References: