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Trial record 1 of 1 for:    NCT05038410
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Study to Investigate the Mechanism of Action of an Oral Enzyme Treatment With Bromelain, Trypsin and Rutoside Versus Placebo in Subjects With OsTeoarthritis (WobeSmart)

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ClinicalTrials.gov Identifier: NCT05038410
Recruitment Status : Active, not recruiting
First Posted : September 9, 2021
Last Update Posted : May 2, 2022
Sponsor:
Collaborators:
Nestlé
Artialis
Information provided by (Responsible Party):
Mucos Pharma GmbH & Co. KG

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.

Condition or disease Intervention/treatment Phase
Osteoarthritis Drug: Wobenzym® Other: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 30, 2021
Estimated Primary Completion Date : July 30, 2022
Estimated Study Completion Date : July 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Active Comparator: 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).
Drug: Wobenzym®
Wobenzym®

Placebo Comparator: PLACEBO
No active ingredients. The active ingredients will be substituted by microcrystalline cellulose.
Other: Placebo
Microcrystalline cellulose




Primary Outcome Measures :
  1. Effects on cartilage biomarkers [ Time Frame: 20 weeks ]
    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)

  2. Effects on markers of innate immune response [ Time Frame: 20 weeks ]
    Change in the expression of M1/M2 Polarization specific membrane markers on fresh blood macrophage, between visit 0 and visit 5 using flow cytometry

  3. Effects on systemic inflammatory markers [ Time Frame: 20 weeks ]
    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)

  4. Effects on cellular pathways [ Time Frame: 20 weeks ]
    Change in plasma proteomic profile using liquid chromatography-tandem mass spectrometry (LC-MS/MS) between visit 0 and visit 5.


Secondary Outcome Measures :
  1. Vital signs and anthropomorphic measurements [ Time Frame: 40 weeks ]
    Changes in systolic and diastolic Blood pressure (BP) in mmHg between visit -1 and visit 6

  2. Vital signs and anthropomorphic measurements [ Time Frame: 40 weeks ]
    Changes in Heart Rate (HR) measured in beats per minute between visit -1 and visit 6

  3. Vital signs and anthropomorphic measurements [ Time Frame: 40 weeks ]
    Changes in Temperature measured in degrees Celsius between visit -1 and visit 6

  4. Vital signs and anthropomorphic measurements [ Time Frame: 40 weeks ]
    Changes in weight measured in kilograms, height measured in centimeters and BMI (weight and height will be combined to calculate BMI in kg/m2 between visit -1 and visit 6

  5. Knee Pain [ Time Frame: 36 weeks ]
    Changes in knee pain at rest and while walking using a Visual Analogue Scale (1 to 100 mm scale where a higher score indicates greater pain intensity) between visit 0 and visit 6

  6. Knee Function [ Time Frame: 36 weeks ]
    Changes in knee function using Knee injury and Osteoarthristis Outcome Score (KOOS). KOOS is a self-administrated questionnaire comprising 5 subscales: pains, symptoms, activities of daily living, sports and recreation function, and quality of life (0 to 100 scale where 100 indicates the best result) between visit 0 and visit 6

  7. Patient global assessment of disease activity (PGADA) [ Time Frame: 36 weeks ]
    Changes in PGADA using a Visual Analogue Scale (1 to 100 mm scale where a higher score indicates a higher level of disease activity /a worse global health) between visit 0 and visit 6

  8. Patient physical activity [ Time Frame: 36 weeks ]
    Effects on subject mobility using a connected device to record heart rate (beats/min between visit 0 and visit 6

  9. Patient physical activity [ Time Frame: 36 weeks ]
    Effects on subject mobility using a connected device to record number of steps/day taken between visit 0 and visit 6

  10. Patient physical activity [ Time Frame: 36 weeks ]
    Effects on subject mobility using a connected device to record number of climbed stairs/day between visit 0 and visit 6

  11. Patient physical activity [ Time Frame: 36 weeks ]
    Effects on subject mobility using a connected device to record intensive exercise minutes/day between visit 0 and visit 6

  12. Patient physical activity [ Time Frame: 36 weeks ]
    Effects on subject mobility using a connected device to record calories burned/day between visit 0 and visit 6minutes/day between visit 0 and visit 6

  13. Body metabolism [ Time Frame: 20 weeks ]
    Effects on body metabolism marker TGF-β1, TGF β 2, TGF-β 3 using immunoassays (Enzyme-linked Immunosorbent assay, ELISA) between visit 0 and visit 5

  14. Clinical chemistry [ Time Frame: 20 weeks ]
    Number of participants with changes in clinical chemistry measurements (concentration of myostatin, hemoglobin, hematocrit, erythrocyte count, TG, TC, LDL, HDL, glucose, hsCRP, uric acid, coagulation markers and key hepatic enzymes) using immunoassays between visit 0 and visit 5

  15. Joint structure modification [ Time Frame: 36 weeks ]
    Effects on joint structure using either MRI Osteoarthritis Knee Score (MOAKS - a semi quantitative scoring tool. Fourteen subregions are defined for scoring of articular cartilage and bone marrow lesions from grade 0 to grade 3. The more the grade increases, the more important the pathology) or Whole-Organ Magnetic Resonance Imaging Score (WORMS - a semi quantitative scoring tool that examines a spectrum of OA-related structural abnormalities including soft tissue, cartilage and bone in the knee at various anatomical subregion locations. The more the score increases, the more important the pathology) between visit 0 and visit 6

  16. Volume of joint effusion [ Time Frame: 36 weeks ]
    Volume of joint effusion by MRI using volumetric segmentation method between visit 0 and visit 6

  17. Tolerance [ Time Frame: 40 weeks ]
    Number of patients with Adverse Events, type of reported adverse events and subject drop out between visit -1 and visit 6

  18. Compliance [ Time Frame: 36 weeks ]
    Tablet count of investigational product between visit 0 and visit 6

  19. Responder rate to treatment [ Time Frame: 36 weeks ]
    Responder rate to treatment defined as changes in knee pain and/or knee function and/or patients disease activity using Pain and/or PGADA and/or KOOS according to recommendations of OMERACT OARSI (Osteoarthritis Research Society International (OARSI) Standing Committee for Clinical Trials Response Criteria Initiative and the Outcome Measures in Rheumatology (OMERACT), defined by either a high improvement in pain or in function >50% and absolute change >20 or an improvement in at least 2 of the 3 following: pain >20% and absolute change >10, function >20% and absolute change >10, patient's global assessment >20% and absolute change >10 (between visit 0 and visit 6



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05038410


Locations
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Belgium
Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim
Antwerpen, Belgium, 2020
Centre Hospitalier Universitaire (CHU) Brugmann
Bruxelles, Belgium, 1020
Cliniques Universitaires Saint Luc UCL
Bruxelles, Belgium, 1200
UZ Brussel
Jette, Belgium, 1090
Centre Hospitalier Régional de la Citadelle
Liège, Belgium, 4000
Sponsors and Collaborators
Mucos Pharma GmbH & Co. KG
Nestlé
Artialis
Investigators
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Principal Investigator: 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
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Responsible Party: Mucos Pharma GmbH & Co. KG
ClinicalTrials.gov Identifier: NCT05038410    
Other Study ID Numbers: 2020CLI
First Posted: September 9, 2021    Key Record Dates
Last Update Posted: May 2, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Wobenzym
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs