Background
Methods
Patients and treatment
Patients met all the following criteria | |
---|---|
Inclusion criteria
| • Men or women, age 45–75; |
• Medial femoro-tibial gonarthrosis (in case of bilateral OA, the most painful knee was evaluated); | |
• Responding to ACR criteria (clinical evaluation and radiological); | |
• Symptoms lasting for more than 6 months; | |
• Global knee pain evaluation over the last 24 hours > 40 mm (without NSAID or other analgesic for more than 48 hours); | |
• K&L II to III (Kellgren and Lawrence evaluated within the last 12 months); | |
• Agreed to banish NSAIDs and analgesics for the duration of the study; | |
• Signed informed consent; | |
• Capable of following the study guidelines; | |
• With health insurance. | |
Exclusion criteria
| Patients with AT LEAST ONE of the following criteria were not enrolled in the study |
• OA disease: | |
o Secondary OA due to metabolic arthropathy: chondrocalcinosis previously | |
o Known or defined by a calcium border on at least one tibiofemoral joint space, gout,… | |
o Predominant symptomatic femoropatellar OA; | |
o Chondromatosis or villo-nodular synovitis of the knee; | |
o Paget’s disease; | |
o Ipsilateral coxarthrosis to the known and symptomatic gonarthrosis; | |
o Recent knee trauma (<1 month) responsible for pain; | |
o Pathologies that could interfere with evaluation (inflammatory and metabolic arthropathy, rheumatoid arthritis, lower limb radiculalgia, arteritis,…). | |
o Joint prosthesis (any site) | |
o Flare affecting another joint | |
• Related to anterior and associated treatments: | |
o Corticosteroid infiltration received to any joint in the month prior enrollment; | |
o Infiltration of hyaluronic acid in the evaluated knee within 6 months before enrollment; | |
o Taking NSAIDs or analgesics in the last 48 hours prior to inclusion; | |
o No changes in their slow-acting anti-OA drugs and anti-OA dietary supplements over the last 6 months (e.g. chondroitin sulfate, diacerein, avocado soybean unsaponifiables, oxaceprol, copper, glucosamine , anti-OA herbal therapy and homeopathy, …); | |
o Taking coumarin anticoagulants and heparins; | |
o General corticosteroid; | |
o Contraindication to paracetamol. | |
• About the product: | |
o Contraindication to the product (Flexofytol) | |
• Related to associated pathologies: | |
o Serious associated diseases (severe liver failure, renal failure, uncontrolled cardiovascular diseases, …). | |
• Regarding the patients: | |
o Pregnant or lactating women; | |
o Premenopausal women not using a contraceptive method; | |
o Patient unable to write; | |
o Patient who participated in a clinical research in the previous 3 months; | |
o Legally responsible adults. |
Serum biomarkers
Statistical analysis
Results
Patients and safety
Patients
| |
N | 22 (M: 7-F: 15) |
Age | 64.3 ± 8.4 years |
Pain history | 48.5 ± 48.2 months |
Knee pain
| |
- Left | 4.6% |
- Right | 31.8% |
- Both | 63.6% |
Radiographic knee OA severity score (K&L)
| |
- I | 13.6% |
- II | 50.0% |
- III | 31.8% |
- IV | 4.6% |
Night pain
| |
-Yes | 59.1% |
-No | 40.9% |
Effusion
| |
-Yes | 31.8% |
-No | 68.2% |
Patients | Blood collection | Adverse events | Concomitant treatment | Drop off | |
---|---|---|---|---|---|
V1 | 22 | 22 | - | - | - |
V2 | 22 | 9.1% | 50.0% | ||
(7 days) | |||||
V3 | 22 | 22 | 14.3% | 45.4% | 1 |
(14 days) | |||||
V4 | 21 | 14.3% | 35.0% | 1 | |
(28 days) | |||||
V5 (84 days) | 20 | 20 | 25% | 55.6% |
Primary endpoint: serum levels of biomarkers
Coll2-1 (nmol/L) | Coll2-1NO2(nmol/L) | Fib3-1 (pmol/L) | Fib3-2 (pmol/L) | CRP (mg/L) | Cartilaps (ng/L) | MPO (μg/L) | |
---|---|---|---|---|---|---|---|
V1 | 302.21 ± 53.78 | 0.71 ± 0.18 | 707.05 ± 178.79 | 580.58 ± 103.09 | 10.42 ± 30.27 | 11.81 ± 7.98 | 27.20 ± 29.05 |
V3 | 315.37 ± 62.35 | 0.77 ± 0.20 | 736.05 ± 157.16 | 600.90 ± 86.04 | 3.82 ± 3.29 | 12.12 ± 5.98 | 20.46 ± 13.15 |
V5 | 257.84 ± 52.78 | 0.80 ± 0.24 | 765.20 ± 261.90 | 636.74 ± 119.73 | 3.10 ± 2.40 | 13.17 ± 4.96 | 21.96 ± 14.65 |
P = 0.002*
|
Secondary endpoints: pain over the last 24 hours and global assessment of disease activity
N | Pain (VAS) | P value | Disease activity | P value | |
---|---|---|---|---|---|
V1 | 22 | 49.41 ± 24.94 | ns | 60.00 ± 22.67 | ns |
V2 | 22 | 50.95 ± 23.85 | ns | 58.32 ± 20.37 | ns |
V3 | 21 | 44.52 ± 27.41 | ns | 48.71 ± 27.37 | ns |
V4 | 20 | 42.20 ± 26.33 | ns | 42.70 ± 25.82 | ns |
V5 | 20 | 39.20 ± 28.96 | ns | 38.85 ± 27.66 | 0.0047* |