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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 5
- 主要终点
- Effects on markers of innate immune response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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:
- •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.
研究组 & 干预措施
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).
干预措施: Wobenzym® (Drug)
PLACEBO
No active ingredients. The active ingredients will be substituted by microcrystalline cellulose.
干预措施: Placebo (Other)
结局指标
主要结局
Effects on markers of innate immune response
时间窗: 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 cellular pathways
时间窗: 20 weeks
Change in plasma proteomic profile using liquid chromatography-tandem mass spectrometry (LC-MS/MS) between visit 0 and visit 5.
Effects on cartilage biomarkers
时间窗: 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 systemic inflammatory markers
时间窗: 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)
次要结局
- Patient physical activity(36 weeks)
- Knee Pain(36 weeks)
- Knee Function(36 weeks)
- Tolerance(40 weeks)
- Vital signs and anthropomorphic measurements(40 weeks)
- Patient global assessment of disease activity (PGADA)(36 weeks)
- Body metabolism(20 weeks)
- Clinical chemistry(20 weeks)
- Compliance(36 weeks)
- Responder rate to treatment(36 weeks)
- Joint structure modification(36 weeks)
- Volume of joint effusion(36 weeks)