ABSTRACT
The safety and efficacy of Hyruan ONE (test product), an intra-articular cross-linked sodium hyaluronate injection, to treat mild-to-moderate knee osteoarthritis was compared with that of Durolane (comparator) in a prospective, active-controlled, parallel-group, double-blind (masked-observed), multicenter non-inferiority study. European patients (n = 284) were randomized 1:1 (test product:comparator) and received one injection of cross-linked hyaluronic acid (60 mg/3 mL). In total, 280 patients completed the study. The primary endpoint of mean change in Western Ontario and McMaster University (WOMAC)-Likert Pain sub-scores from baseline at week 13 revealed changes of -5.59 and -5.54 for the test and comparator groups, respectively, demonstrating non-inferiority of the test product (difference, -0.05 [95% confidence interval, -0.838 to 0.729]). Secondary endpoint results, which included changes in WOMAC-Likert Pain sub-score from baseline to 26 weeks post-injection and changes in WOMAC-Likert Total score and Physical Function and Stiffness sub-scores, changes in patients' and investigators' global assessments, use of rescue medication, and responder rates at 13 and 26 weeks post-injection were similar between the groups. Incidence of adverse events was also similar. In both groups, most treatment-emergent adverse events were mild/moderate. Hyruan ONE was non-inferior to the comparator at 13 weeks post-injection in European patients with mild-to-moderate knee osteoarthritis.
ABSTRACT
OBJECTIVE: The aim: In this study, we present a sub-analysis of physical functionality in sufferers of mild knee osteoarthritis (OA) following a clinical assessment of a novel nutraceutical supplement Tregocel® complementary to standard treatment. PATIENTS AND METHODS: Materials and methods: We evaluated the results of a multicenter, open-label, single-arm efficacy and safety evaluation of a polyherbal nutraceutical, performed in subjects with symptomatic, mild knee OA (n = 107, 59.7 ± 10.8 yrs, 68.2% female) over 36 weeks. Physical function was assessed using a standardized walking challenge (6-min walk test), combined with WOMAC indices and leg flexion measurements. Sub-analysis was performed using a linear mixed model that tracked changes in the walking challenge outcomes over time, adjusted for age, gender, and OA duration. RESULTS: Results: Walking distance was significantly improved with the duration of nutraceutical use, increasing by 0.72 m (95% CI: 0.56, 0.88) per week of product administration. Similarly, there were significant decreases in WOMAC indices per week for stiffness (-1.6, 95% CI: -1.8, 1.4), daily functioning (-13.5, 95% CI: 14.9, 11.9) and global outcome (-19.2, 95% CI -21.3 - -17.1). Furthermore, supine heel-to-high flexion distance was improved relative to the duration of nutraceutical use. CONCLUSION: Conclusions: The use of a polyherbal nutraceutical resulted in clinical improvements in several indices of physical functioning in mild knee OA suffers. Trial registration: NCT03636035.
Subject(s)
Osteoarthritis, Knee , Dietary Supplements , Female , Humans , Male , Osteoarthritis, Knee/drug therapy , Range of Motion, Articular , Treatment Outcome , WalkingABSTRACT
Knee osteoarthritis (OA) accounts for approximately 85% of the burden of OA worldwide. Knee OA is a whole joint disorder involving structural alterations in the hyaline articular cartilage, subchondral bone, ligaments, capsule, synovium, and periarticular muscles. The complex knee OA pathogenesis includes mechanical, inflammatory, and metabolic factors, eventually leading to the synovial joint's structural destruction and failure. This review aims to present an overview of current knowledge on dietary supplements, such as glucosamine, chondroitin, methylsulfonylmethane, diacerein, avocado-soybean unsaponifiables, curcuminoids, as well as boswellic acids. Results originating from several small studies with natural products in managing knee OA are encouraging. However, additional well-designed placebo-controlled clinical trials are required.
Subject(s)
Osteoarthritis, Knee , Persea , Dietary Supplements , Glucosamine/therapeutic use , Humans , Osteoarthritis, Knee/drug therapy , Plant ExtractsABSTRACT
INTRODUCTION: The objective of this study was to compare a single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) versus placebo in treating moderate-to-severe symptomatic knee osteoarthritis. METHODS: Subjects with primary osteoarthritis knee pain (Kellgren and Lawrence grade 2-3) were randomly assigned to intra-articular HA-HL or placebo in a prospective, double-blind, 24-week study. The primary outcome variable was change from screening to week 24 of a Visual Analogue Scale (VAS) pain score. Secondary outcomes included Lequesne's algofunctional index, EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) response and rescue medication usage. RESULTS: In a total of 692 randomized patients, a rapid decrease was observed in mean VAS pain score from baseline to week 1 (26 ± 24 mm in the HA-HL group vs. 23 ± 23 mm in the placebo group); pain intensity continued to decrease during 24 weeks of follow-up, reaching a mean change from baseline of 35 ± 28 mm vs. 32 ± 27 mm at week 24. Mixed model analysis demonstrated statistically significant differences between groups in favor of the HA-HL group at weeks 1, 6, 12, and 24. HA-HL was also more effective than placebo in improving Lequesne's algofunctional index, OMERACT-OARSI response, and health-related quality of life. The use of rescue medication (paracetamol 500 mg tablets; ≤ 6 per day) was lower in the HA-HL group. Both treatments were similarly well tolerated. CONCLUSIONS: A single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) is effective in providing fast, sustained, and clinically relevant reductions in pain, functional limitation, and health-related quality of life that were apparent at 1 week after the intra-articular injection and maintained throughout the 24-week follow-up in subjects with painful knee osteoarthritis, with a good safety profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03200288.
ABSTRACT
BACKGROUND: This study aimed to provide clinical information on general and joint performance from individuals taking Tregocel® (containing curcuminoid and extracts of the herbs Harpagophytum procumbens, Boswellia serrata, Apium graveolens, and Zingiber officinale) alongside a standard therapy of symptomatic mild knee osteoarthritis (OA). METHODS: This was a multicenter, open-label, prospective, single-arm study, in which Tregocel® was supplemented for 36 weeks. Participants with symptomatic mild knee OA requiring pharmacologic treatment for pain were enrolled. Physical performance (6-minute walk test, WOMAC-pain and functional domain, and heel-thigh distance flexion test), general performance (WOMAC questionnaire), and VAS (Visual Analogue Scale) assessment of knee pain, as well as anti-inflammatory and analgesic medication consumption, were assessed. RESULTS: Between January and April 2019, 107 participants were enrolled and analysed in per protocol population. Mean age was 59.7 (SD 10.8) years, and there were 68.2% women. Mean observation time was 291.1 (SD 7.7) days. Mean increase in 6MWT result observed at the end of the study was 26.0 (SD 30.4) m (p < 0.001). Median VAS score decreased from 60.0 (IQR 50-72) mm at the beginning of the study to 21.0 (IQR 14-30) mm after 36 weeks of product administration (p < 0.001). Regular knee OA medications were taken in 99.1% of subjects at baseline decreasing to 55.1% at the end of the Tregocel® supplementation. CONCLUSIONS: During Tregocel® supplementation, participants observed improved functional capacity confirmed in the distance in 6MWT and in the heel-thigh distance flexion test, decreased level of pain, and improved WOMAC scores for all domains.
