INTRODUCTION: Some argued that clinical efficacy of Chondroitin Sulfate (CS) could vary upon the product origin. The objective of this trial is to compare the effect of 2 CS medicinal products from different origin: Structum(®) (avian, 1000mg/day) and Chondrosulf(®) (bovine, 1200mg/day).
METHODS: This was a randomized, double-blind, double placebo, active-controlled, parallel-group study using a non-inferiority design. Symptomatic osteoarthritis of the knee patients, according to American College of Rheumatology criteria, aged 50-80 years received either Structum(®) (500mg BID) or Chondrosulf(®) (400mg TID) during 24 weeks. Inclusion criteria were: global pain in the target knee ≥ 40mm on a Visual Analog Scale (VAS 0-100), a Lequesne's Algofunctional Index (LFI) score ≥ 7 (range: 0-24) and a radiological Kellgren-Lawrence grade 2 or 3. Primary outcome was the mean change over 24 weeks of pain VAS and LFI score. Secondary outcomes were patient's and physician's global assessments, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International responders rate, analgesics intake and Medical Outcomes Survey Short-Form 12 (SF-12). Safety was assessed by recording adverse events. A non-inferiority test was performed on the Structum(®)-Chondrosulf(®) difference for VAS and LFI score changes. Predefined non inferiority limit was settled as the lower limit of the 95% CI above -5mm and -1pt for pain VAS and LFI score respectively.
RESULTS: 837 patients were randomized: 817 available for the full analysis dataset (FAS), 692 for the per protocol (PP) analysis. No statistical and clinical differences were observed for demographics and disease characteristics between the 2 groups. PP analysis showed no difference between groups on mean variations of pain VAS or LFI scores over 24 weeks. Mean Pain VAS decreased by 23.9mm (17.5) in Structum(®) group and 23.8mm (17.2) in Chondrosulf(®) group (difference: 0.012 [CI95%: -2.6 ; 2.6]). Mean LFI score decreased by 3.2 (2.4) and 3.1 (2.4) respectively (difference: 0.139 [CI95%: -0.2 ; 0.5]). The lower limits of the 2 CI were above predefined non inferiority margin, which demonstrated the non inferiority of Structum(®) in comparison with Chondrosulf(®). FAS analysis gave similar results. Secondary efficacy outcomes analysis showed the same trends. Responders rate were 76.3% and 73.8% respectively (PP, W24). Treatments were well tolerated: 2.4% in Structum(®) group and 4.5% in Chondrosulf(®) group withdrew from the study for safety reasons.
CONCLUSION: Structum(®) and Chondrosulf(®) were equally effective in reducing functional impairment and relieving pain over 6 months in knee osteoarthritis patients, without any safety concerns.
TRIAL REGISTRATION: http://www.controlled-trials.com Number: ISRCTN04305346.
OBJECTIVE: Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) (equivalence study) and vs placebo (superiority study) during 3 months, in patients with knee osteoarthritis (OA).
DESIGN: Comparative, double-blind, randomized, multicenter study, including 353 patients of both genders over 45 years with knee OA. Minimum inclusion criteria were a Lequesne index (LI) ≥ 7 and pain ≥ 40 mm on a visual analogue scale (VAS). LI and VAS were assessed at baseline and after 1-3 months. Equivalence between CS was tested using the per-protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure.
RESULTS: After 3 months of follow-up, no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400. Patients treated with CS 1200 or CS 3*400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI (<0.001) and VAS (P < 0.01). No significant difference in terms of security and tolerability was observed between the three groups.
CONCLUSION: This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo, and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient.
BACKGROUND: Oral glucosamine and chondroitin sulfate, alone and in combination, have been used worldwide for the treatment of osteoarthritis (OA), but their efficacy is controversial. This clinical study was aimed at investigating the potential of a dietary supplement containing glucosamine and chondroitin sulfate in combination with derivatives of quercetin, a naturally occurring flavonoid, (GCQ supplement) for knee OA care.
RESULTS: A randomized, double-blind, placebo-controlled study was conducted in 40 Japanese subjects with symptomatic knee OA. Subjects were randomly assigned to GCQ supplement (1200 mg glucosamine hydrochloride, 60 mg chondroitin sulfate and 45 mg quercetin glycosides per day) or placebo and the treatment and follow-up were continued for 16 weeks. The results of symptomatic efficacy assessment based on Japanese Orthopaedic Association criteria showed that scores for two of the four symptom/function subscales, as well as the aggregate scores, were significantly improved at week 16 or earlier in the GCQ group compared to the placebo group. Moreover, analyses of cartilage metabolism biomarkers showed a trend of improvement in type II collagen synthesis/degradation balance in the GCQ group during follow-up.
CONCLUSION: GCQ supplement was thought to be more effective than placebo in decreasing the intensity of knee OA-associated clinical symptoms.
This pilot study aimed to evaluate the correlation between clinical symptoms and cartilage volume through MRI in patients with knee osteoarthritis after 48 weeks of treatment with Structum®. Multicenter, double-blind, placebo-controlled, parallel-group study. Symptomatic knee osteoarthritis patients aged 50-75 years received either Structum® (500 mg twice daily; N = 22) or placebo (N = 21) during 48 weeks. Inclusion criteria were global pain in the target knee ≥30 mm (VAS 0-100) and radiological Kellgren-Lawrence grade 2 or 3. Clinical assessments included Lequesne index and VAS for pain on motion, at baseline, 24 and 48 weeks, and MRI at baseline and at 24 and 48 weeks. Global and compartments cartilage volume, joint cartilage abnormalities, meniscal lesions, ligaments abnormalities, synovitis, synovial effusion, osteophytes, subchondral cysts, popliteal cysts and subchondral oedema were quantified. The quantitative and qualitative reproducibility of MRI was tested by the Spearman correlation coefficient and kappa coefficients, respectively. Treatments were compared by an analysis of covariance with baseline value as covariate. Groups were comparable at baseline for demographics, disease characteristics, and cartilage volumes. A significant inter-readers correlation was seen for the assessment of cartilage volumes, number of cysts, and osteophytes (correlation coefficients from 0.951 to 0.980 within investigator and from 0.714 to 0.957). After 48 weeks, symptoms improved in both groups. The total cartilage volume increased in the Structum® group (+180 mm(3) + SD) which opposed to a loss in the placebo (-46 mm(3) + SD; NS). No statistically significant differences between groups were observed for the other MRI parameters. No correlations were evidenced between key MRI parameters changes and symptoms. The difference in the evolution of cartilage volume between the two groups could reflect a structure modifying effect of Structum®. This pilot study confirms the usefulness of quantitative and qualitative MRI as a sensitive tool to assess a structure modifying drugs in knee osteoarthritis.
OBJECTIVE: To determine the effect of chondroitin sulphate (CS) treatment on cartilage volume loss, subchondral bone marrow lesions (BML), synovitis and disease symptoms in patients with knee osteoarthritis (OA).
METHODS: In this pilot multicentre, randomised, double-blind, controlled trial in primary knee OA, 69 patients with clinical signs of synovitis were randomised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily. Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months; synovial membrane thickness was assessed at baseline and at 6 months.
RESULTS: The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee (p=0.030), lateral compartment (p=0.015) and tibial plateaus (p=0.002), with significance persisting at 12 months. Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment (p=0.035) and the lateral femoral condyle (p=0.044). Disease symptoms were similar between the two groups.
CONCLUSION: CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment, and BML at 12 months. These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA.
In the present study, we aimed to investigate the potential effect of a glucosamine (1,200 mg/day)-based dietary supplement combined with chondroitin sulfate and three antioxidant micronutrients, namely methylsulfonylmethane, guava leaf extract, and vitamin D (test supplement) on osteoarthritis (OA) of the knee. A 16-week, randomized, double-blinded, placebo-controlled trial was conducted involving 32 subjects with symptomatic knee OA. Clinical outcomes were measured using the Japanese Knee Osteoarthritis Measure (JKOM) for symptoms and a study diary-based visual analog scale (diary VAS) for pain at baseline and at weeks 4, 8, 12 and 16 during the 16-week intervention period. Furthermore, biomarkers for cartilage type II collagen degradation (C2C) and synovitis hyaluronan (HA) were measured. As compared with the baseline, the JKOM pain subscale was significantly improved at all of the four assessment time points in the test group, but was not at any time point in the placebo group. On the other hand, all of the four symptom subscales and the aggregated total symptoms were significantly improved in the two groups at one or more time points. However, all of these clinical improvements were greater in extent in the test group than in the placebo group, and there were significant differences between groups in the magnitude of changes from baseline for one subscale 'general activities' and the aggregated total symptoms at week 8 (P<0.05). The results of efficacy assessments with the diary VAS showed that all of the three pain subscales were significantly improved only in the test group at almost all the time points. Moreover, serum levels of C2C and HA were decreased by 10 and 25%, respectively, at week 16 in the test group, albeit not statistically significant, without any detectable changes in the placebo group. In conclusion, although the results obtained in this study were not conclusive, the tested glucosamine-based combination supplement is likely to have a beneficial effect on pain and other symptoms associated with knee OA.
BACKGROUND: The purpose of this study was to determine whether sedentary obese women with knee OA initiating an exercise and weight loss program may experience more beneficial changes in body composition, functional capacity, and/or markers of health following a higher protein diet compared to a higher carbohydrate diet with or without GCM supplementation.
METHODS: Thirty sedentary women (54 ± 9 yrs, 163 ± 6 cm, 88.6 ± 13 kg, 46.1 ± 3% fat, 33.3 ± 5 kg/m2) with clinically diagnosed knee OA participated in a 14-week exercise and weight loss program. Participants followed an isoenergenic low fat higher carbohydrate (HC) or higher protein (HP) diet while participating in a supervised 30-minute circuit resistance-training program three times per week for 14-weeks. In a randomized and double blind manner, participants ingested supplements containing 1,500 mg/d of glucosamine (as d-glucosamine HCL), 1,200 mg/d of chondroitin sulfate (from chondroitin sulfate sodium), and 900 mg/d of methylsulfonylmethane or a placebo. At 0, 10, and 14-weeks, participants completed a battery of assessments. Data were analyzed by MANOVA with repeated measures.
RESULTS: Participants in both groups experienced significant reductions in body mass (-2.4 ± 3%), fat mass (-6.0 ± 6%), and body fat (-3.5 ± 4%) with no significant changes in fat free mass or resting energy expenditure. Perception of knee pain (-49 ± 39%) and knee stiffness (-42 ± 37%) was decreased while maximal strength (12%), muscular endurance (20%), balance indices (7% to 20%), lipid levels (-8% to -12%), homeostasis model assessment for estimating insulin resistance (-17%), leptin (-30%), and measures of physical functioning (59%), vitality (120%), and social function (66%) were improved in both groups with no differences among groups. Functional aerobic capacity was increased to a greater degree for those in the HP and GCM groups while there were some trends suggesting that supplementation affected perceptions of knee pain (p < 0.08).
CONCLUSIONS: Circuit style resistance-training and weight loss improved functional capacity in women with knee OA. The type of diet and dietary supplementation of GCM provided marginal additive benefits.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT01271218.
OBJECTIVE: To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate (CS) therapy in patients with osteoarthritis (OA) of the hand.
METHODS: This investigator-initiated, single-center, randomized, double-blind, placebo-controlled clinical trial included 162 symptomatic patients with radiographic evidence of hand OA (American College of Rheumatology criteria). Inclusion criteria included patient's assessment of global spontaneous hand pain of at least 40 mm on a 0-100-mm visual analog scale (VAS) and functional impairment of at least 6 (0-30 scale) on the Functional Index for Hand OA (FIHOA) in the most symptomatic hand. Patients received either 800 mg of CS (n = 80 patients) or placebo (n = 82 patients) once daily for 6 months and were analyzed in an intent-to-treat approach. The two primary outcomes were the change in the patient's assessment of global spontaneous hand pain and in hand function (by FIHOA score) from baseline to month 6. Secondary outcomes were improvement in grip strength, duration of morning stiffness, acetaminophen consumption, and the investigator's global impression of treatment efficacy.
RESULTS: There was a significantly more pronounced decrease in the patient's global assessment of hand pain in the CS group than in the placebo group (difference VAS scores -8.7 mm; P = 0.016). Hand function improved significantly more in the CS group than in the placebo group (difference in FIHOA scores -2.14; P = 0.008). There was a statistically significant between-group difference in favor of CS for the duration of morning stiffness and for the investigator's global impression of treatment efficacy. Changes in grip strength, acetaminophen consumption, and safety end points were not significantly different between the two groups.
CONCLUSION: This study demonstrates that CS improves hand pain and function in patients with symptomatic OA of the hand and shows a good safety profile.
