OsteoarthritisWobeSmartNCT05038410
Study to Investigate the Mechanism of Action of an Oral Enzyme Treatment With Bromelain, Trypsin and Rutoside Versus Placebo in Subjects With OsTeoarthritis
A study testing Wobenzym® in people with Osteoarthritis, run by Mucos Pharma GmbH & Co. KG at 5 sites in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 100 years
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- Wobenzym®
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 5 sitesBelgium
- Study dates
- 30 Apr 2021to 5 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 36Show fewer
- Analgesics to manage knee pain 24 hours before inclusion visit;
- 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
- severe liver and/or kidney damage
- hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- Hypersensitivity or allergy to the product components, and pineapple;
- Treatments based on strontium ranelate, bisphosphonates, selective estrogen-receptor modulator (SERM) and parathormone (PTH) in the last 12 months;
- Treatment based on zoledronate in the last 2 years;
- Treatment based on denosumab in the last 6 months;
- Treatment with anticoagulants and/or anti-platelet agents
- Related to associated diseases:
- Any severe, uncontrolled and limiting disease left to the Investigator's discretion;
- Patient with widespread pain/depression (e.g. fibromyalgia);
- Lower or upper extremity surgery or fracture in the last 6 months;
- Anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the target knee;
- Severe alteration of mobility enabling functional evaluation.
- Related to subjects
- Close collaborators to the investigational team, the study coordinator (ARTIALIS) or to the Sponsor;
- Currently participating or having participated in another therapeutic clinical trial in the three previous months;
- Having made a blood donation in the past month;
- Under guardianship or judicial protection;
- Pregnancy, breastfeeding, planned conception, or premenopausal women without effective contraception (tablet, patch, ring, diaphragm, implant and intrauterine device, tubal ligation or hysterectomy);
- Counter-indication to an MRI examination.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Belgium5 sites
Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim
Antwerp, 2020
Centre Hospitalier Universitaire (CHU) Brugmann
Brussels, 1020
Cliniques Universitaires Saint Luc UCL
Brussels, 1200
UZ Brussel
Jette, 1090
Centre Hospitalier Régional de la Citadelle
Liège, 4000
About this study
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
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.
Read the 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
- Being tested
- Wobenzym®, Placebo
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Wobenzym®Drug
Wobenzym®
PlaceboOther
Microcrystalline cellulose
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Wobenzym® |
| PLACEBO | Placebo comparator | No active ingredients. The active ingredients will be substituted by microcrystalline cellulose. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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)
Measured: 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.
Measured: 20 weeks
Secondary outcomes (19)
Vital signs and anthropomorphic measurements
Changes in systolic and diastolic Blood pressure (BP) in mmHg between visit -1 and visit 6
Measured: 40 weeks
Vital signs and anthropomorphic measurements
Changes in Heart Rate (HR) measured in beats per minute between visit -1 and visit 6
Measured: 40 weeks
Vital signs and anthropomorphic measurements
Changes in Temperature measured in degrees Celsius between visit -1 and visit 6
Measured: 40 weeks
Vital signs and anthropomorphic measurements
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
Measured: 40 weeks
Knee Pain
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
Measured: 36 weeks
Knee Function
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
Measured: 36 weeks
Patient global assessment of disease activity (PGADA)
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
Measured: 36 weeks
Patient physical activity
Effects on subject mobility using a connected device to record heart rate (beats/min between visit 0 and visit 6
Measured: 36 weeks
Patient physical activity
Effects on subject mobility using a connected device to record number of steps/day taken between visit 0 and visit 6
Measured: 36 weeks
Patient physical activity
Effects on subject mobility using a connected device to record number of climbed stairs/day between visit 0 and visit 6
Measured: 36 weeks
Patient physical activity
Effects on subject mobility using a connected device to record intensive exercise minutes/day between visit 0 and visit 6
Measured: 36 weeks
Patient physical activity
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
Measured: 36 weeks
Body metabolism
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
Measured: 20 weeks
Clinical chemistry
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
Measured: 20 weeks
Joint structure modification
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
Measured: 36 weeks
Volume of joint effusion
Volume of joint effusion by MRI using volumetric segmentation method between visit 0 and visit 6
Measured: 36 weeks
Tolerance
Number of patients with Adverse Events, type of reported adverse events and subject drop out between visit -1 and visit 6
Measured: 40 weeks
Compliance
Tablet count of investigational product between visit 0 and visit 6
Measured: 36 weeks
Responder rate to treatment
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
Measured: 36 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2021
- Study start30 Apr 2021
- Primary completion5 Oct 2022
- Study completion5 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mucos Pharma GmbH & Co. KG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Société des Produits Nestlé (SPN), Artialis
- Responsible party
- Sponsor
- Investigators
- Valerie Badot, Principal investigator, Centre Hospitalier Universitaire (CHU) BrugmannDidier Urbin-Choffray, Principal investigator, Centre Hospitalier Régional de la CitadelleKarl Brabants, Principal investigator, Ziekenhuis Netwerk Antwerpen (ZNA) MiddelheimJean-Emile Dubuc, Principal investigator, Cliniques Universitaires Saint Luc UCLSiddhartha Lieten, Principal investigator, Universitair Ziekenhuis Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05038410
- Sponsor's protocol ID
- 2020CLI
- Acronym
- WobeSmart
- Status last verified
- Oct 2022
- First submitted
- 25 May 2021
- Last updated
- 22 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 40803821
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05038410
- Acronym / sponsor ID
- WobeSmart / 2020CLI
- Conditions
- Osteoarthritis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Mucos Pharma GmbH & Co. KGIndustry (pharma, biotech, devices)
- Collaborators
- Société des Produits Nestlé (SPN), Artialis
- Study start
- 30 Apr 2021 (actual)
- Primary completion
- 5 Oct 2022 (actual)
- Study completion
- 5 Oct 2022 (actual)
- First posted
- 9 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Wobenzym® | Active comparator | Drug: 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). |
| PLACEBO | Placebo comparator | Other: PlaceboNo active ingredients. The active ingredients will be substituted by microcrystalline cellulose. |
Who may qualify
- Ages
- 40 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female ≥ 40 years of age and with BMI ≤ 35 kg/m2;
- Uni- or bilateral femorotibial knee OA :
- 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.
Key exclusion criteria (36 listed)
- 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.
- Analgesics to manage knee pain 24 hours before inclusion visit;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Wobenzym®Wobenzym® | Drug | Wobenzym® |
| PlaceboMicrocrystalline cellulose | Other | PLACEBO |
Primary outcome
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)
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
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)
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.
19 secondary outcomes
Vital signs and anthropomorphic measurements
Time frame: 40 weeks
Vital signs and anthropomorphic measurements
Time frame: 40 weeks
Vital signs and anthropomorphic measurements
Time frame: 40 weeks
Vital signs and anthropomorphic measurements
Time frame: 40 weeks
Knee Pain
Time frame: 36 weeks
Knee Function
Time frame: 36 weeks
Patient global assessment of disease activity (PGADA)
Time frame: 36 weeks
Patient physical activity
Time frame: 36 weeks
Patient physical activity
Time frame: 36 weeks
Patient physical activity
Time frame: 36 weeks
Patient physical activity
Time frame: 36 weeks
Patient physical activity
Time frame: 36 weeks
Body metabolism
Time frame: 20 weeks
Clinical chemistry
Time frame: 20 weeks
Joint structure modification
Time frame: 36 weeks
Volume of joint effusion
Time frame: 36 weeks
Tolerance
Time frame: 40 weeks
Compliance
Time frame: 36 weeks
Responder rate to treatment
Time frame: 36 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Derived from this study: PubMed 40803821Henrotin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Valerie Badot principal investigator
Centre Hospitalier Universitaire (CHU) Brugmann
Didier Urbin-Choffray principal investigator
Centre Hospitalier Régional de la Citadelle
Karl Brabants principal investigator
Ziekenhuis Netwerk Antwerpen (ZNA) Middelheim
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Wobenzym® in people with Osteoarthritis, run by Mucos Pharma GmbH & Co. KG at 5 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effects on cartilage biomarkers (time frame: 20 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05038410, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.