Evaluation of FLEXOFYTOL® Versus PLACEBO

Study Overview
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Brief Summary
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This study is a prospective, randomized, double-blind, placebo-controlled with 3 parallel-groups and multicenter trial in patients suffering from knee OA (osteoarthrosis). A first exploratory non comparative study (TILFLEXY002, NCT01909037, Henrotin et al., 2014 BMC Complementary and Alternative Medicine) evaluated the efficacy of FLEXOFYTOL® at the dose of 2x3 caps/day, during a 3-month period, in 22 patients suffering from knee OA, on the serum levels of cartilage-specific and inflammatory biomarkers, on the evaluation of pain and on the global patient assessment of disease activity. This study demonstrated a statistically significant decrease of sColl2-1 cartilage specific biomarker, an early decrease of the ultrasensitive C-reactive protein (CRP), an improvement of the global assessment of the disease by the patient as well as a good tolerance and compliance for the treatment. Results of this exploratory study are encouraging and justify the setup of a randomized, placebo-controlled double blind and dose-ranging trial.

Detailed Description
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150 patients suffering from symptomatic knee OA will be randomized in 3 parallel groups (50 patients per group). Each patient will be enrolled in the study for 6 months including 4 visits: Inclusion visit (T0), follow-up visits after 1 month (T1), 3 months (T3) and 6 months (T6). A. Primary objective - Evaluate the efficacy of two different dosages of FLEXOFYTOL® versus PLACEBO on arthritis related biomarker coll2-1 and on patient assessment of disease activity in patients suffering from knee OA after a 3 months treatment B. Secondary objectives Evaluate the efficacy of two different dosages of FLEXOFYTOL® versus PLACEBO on arthritis-related and inflammatory biomarkers. Evaluate the efficacy of two different dosages of FL EXOFYTOL® versus PLACEBO on pain and function. Evaluate the tolerance, the compliance and the patients' satisfaction. Evaluate the use of rescue treatments i.e. Paracetamol and oral non-steroidal antiinflammatory drugs (NSAIDs) during the study.

Official Title
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Evaluation of Efficacy, Tolerance, and Dose Effects of a Curcuma Extract (FLEXOFYTOL®) Versus PLACEBO in Patients With Knee osteoARthritis (COPRA)

Conditions
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Osteoarthritis

Intervention / Treatment
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* Dietary Supplement: FLEXOFYTOL®
* Other: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between the age of 45 and 80 Exclusion Criteria: Artialis (study coordinator) or Tilman (Sponsor) 's employees Participation to a therapeutic clinical trial in the last 3 months Under guardianship or judicial protection

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Group A: FLEXOFYTOL® high dosage | Dietary Supplement: FLEXOFYTOL®<br>* The product FLEXOFYTOL® is bio-optimized curcumin.<br>* Other names: curcuma extract;|
| Active Comparator: Group B<br>Group B: FLEXOFYTOL® low dosage | Dietary Supplement: FLEXOFYTOL®<br>* The product FLEXOFYTOL® is bio-optimized curcumin.<br>* Other names: curcuma extract;|
| Placebo Comparator: Group C<br>Group C: PLACEBO | Other: PLACEBO<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of serum levels of sColl2-1 biomarker between T0 and T3 by specific immunoassays (Enzyme-linked Immunosorbent assay, ELISA). |  | 3 months (between T0 and T3 visit) | 
| Variation of Global assessment of disease activity by the patient using a Visual analogue scale (VAS) between T0 and T3. |  | 3 months (between T0 and T3 visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of serum levels of sColl2-1 (type II collagen degradation) and ultrasensitive CRP (C-reactive protein) biomarkers by specific immunoassays (Enzyme-linked Immunosorbent assay, ELISA). |  | 6 months (between T0 and T6 visit) | 
| Mean knee pain over the last 24 hours using a visual analogue scale (VAS). |  | 6 months (between T0 and T6 visit) | 
| Global assessment of disease activity using a visual analogue scale (VAS). |  | 6 months (between T0 and T6 visit) | 
| Evaluation of Incidence of Emergent Adverse Events (AE), drop-outs and safety issues using blood safety analyses on patients with AE (Tolerance). |  | 6 months (between T0 and T6 visit) | 
| Count the capsules in investigation kits brought back by the patient. |  | 6 months (between T0 and T6 visit) | 
| Dosage by UHPLC-MS/MS and monitoring of curcumin blood level to assess patient compliance. |  | 6 months (between T0 and T6 visit) | 
| Evaluation of Patient's satisfaction by Likert scale. |  | 6 months (between T0 and T6 visit) | 
| Evaluate the use of rescue treatments i.e. Paracetamol and oral non-steroidal anti-inflammatory drugs (NSAIDs) during the study. |  | 6 months (between T0 and T6 visit) | 
| Secondary outcome 8: Knee injury Osteoarthritis Outcome Score (KOOS) index and its subscale scores using a self-administered questionnaire. |  | 6 months (between T0 and T6 visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OsteoArthritis; FLEXOFYTOL®; Curcuma; biomarkers