IMPORTANCE: Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory.
OBJECTIVE: To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels.
DESIGN, SETTING, AND PARTICIPANTS: A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013.
INTERVENTIONS: Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years.
MAIN OUTCOMES AND MEASURES: Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI).
RESULTS: Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text].
CONCLUSIONS AND RELEVANCE: Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01176344; anzctr.org.au Identifier: ACTRN12610000495022.
PURPOSE: The aim of this study was to investigate the efficacy and tolerability of GCSB-5, a mixture of 6 purified herbal extracts, in treating hand osteoarthritis (OA).
METHODS: A randomized, double-blind, placebo-controlled trial enrolled 220 patients with hand OA who had baseline a visual analog scale joint pain score of >30 of 100 mm at 3 hospitals between September 2013 and November 2014. After randomization, patients were allocated to receive oral GCSB-5 600 mg or placebo, bid for 12 weeks. The primary end point was the change in the Australian/Canadian OA Hand Index (AUSCAN)-defined pain score at 4 weeks relative to baseline. Secondary end points included the frequency Outcome Measures in Rheumatology-OA Research Society International (OMERACT-OARSI)-defined response at 4, 8, 12, and 16 weeks after randomization.
FINDINGS: The allocated treatment was received by 109 and 106 patients in the GCSB-5 and placebo groups, respectively. At 4 weeks, the median (interquartile range) change in AUSCAN pain score relative to baseline was significantly greater in the GCSB-5 group than in the placebo group (-9.0 [-23.8 to -0.4] vs -2.2 [-16.7 to 6.0]; P = 0.014), with sustained improvement at 8, 12, and 16 weeks (P = 0.039). The GCSB-5 group also had a significantly greater OMERACT-OARSI-defined response rate than did the placebo group at 4 weeks (44.0% vs 30.2%), 8 weeks (51.4% vs 35.9%), 12 weeks (56.9% vs 40.6%), and 16 weeks (50.5% vs 37.7%) (P = 0.0074). The 2 treatments exhibited comparable safety profiles.
IMPLICATIONS: GCSB-5 was associated with improved symptoms of hand OA, with good tolerability, in these patients. GCSB-5 may be a well-tolerated alternative of, or addition to, the treatment of hand OA. ClinicalTrials.gov identifier: NCT01910116.
BACKGROUND: Tong Luo Hua Shi (TLHS) is a new formulation of the traditional Tibetan medicine Wu-wei-gan-lu that has been used for the treatment of rheumatoid arthritis (RA) for hundreds of years in China. This study aimed to evaluate the efficacy and safety of TLHS in patients with RA.
METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding study performed in patients with active RA from five medical centers. Patients received three doses (4.8, 3.6, or 2.4 g/day po) of TLHS or placebo (tid po) for 8 weeks. Blood sampling, physical examination, and assessment of the American College of Rheumatology (ACR) 20 % improvement (ACR20) criteria were performed before and every 2 weeks after starting treatment. The primary endpoint was the ACR20. The secondary endpoints included safety.
RESULTS: A total of 240 participants were screened and 236 patients were randomized (n = 59/group); 20 dropped out. After 8 weeks, ACR20 improvements in the TLHS 4.8 g and 3.6 g groups were significantly higher than in the placebo group (P < 0.01 and P < 0.05, respectively). ACR50 improvement in the TLHS 4.8 g group was significantly higher compared with the placebo group (P < 0.01). Symptoms of RA were significantly relieved in the TLHS groups. In the TLHS groups, insomnia (n = 1), gastroenteric reactions (n = 2), arrhythmia (n = 1), and minor hepatic lesion (n = 1) were reported; in the placebo group, hepatic dysfunction (n = 1) was reported (P = 0.878).
CONCLUSIONS: TLHS improved the symptoms of patients with RA according to the ACR20. Moreover, TLHS was safe.
TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-12003871 . Registered on 1 January 2012.
OBJECTIVE: Vitamin D has an important immunomodulatory effect, but there are no trials that directly address the boosting of serum levels of 25-hydroxyvitamin D (25[OH]D) in juvenile-onset systemic lupus erythematosus (SLE). The aim of this study was to evaluate the effect of vitamin D supplementation on disease activity and fatigue in juvenile-onset SLE.
METHODS: This study was a randomized, double-blind, placebo-controlled, 24-week trial. Forty juvenile-onset SLE patients were randomized (1:1) to receive oral cholecalciferol 50,000 IU/week (juvenile-onset SLE-VitD) or placebo (juvenile-onset SLE-PL). Medications remained stable throughout the study. Serum levels of 25(OH)D were measured using radioimmunoassay. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measurement (ECLAM). Fatigue was assessed using the Kids Fatigue Severity Scale (K-FSS).
RESULTS: At baseline, groups were similar regarding age, body mass index, organ involvement, glucocorticoid dose, use of immunosuppressive drugs, SLEDAI, ECLAM, K-FSS, and levels of 25(OH)D. After 24 weeks, the mean level of 25(OH)D was higher in the juvenile-onset SLE-VitD group than in the juvenile-onset SLE-PL group (P < 0.001). At the end of the intervention, a significant improvement in SLEDAI (P = 0.010) and in ECLAM (P = 0.006) was observed in the juvenile-onset SLE-VitD group compared to the juvenile-onset SLE-PL group. Regarding fatigue evaluation, a reduction of fatigue related to social life score was found in the juvenile-onset SLE-VitD group compared to the juvenile-onset SLE-PL group (P = 0.008). Cholecalciferol was well tolerated with no serious adverse events.
CONCLUSION: This study suggests that cholecalciferol supplementation for 24 weeks is effective in decreasing disease activity and improving fatigue in juvenile-onset SLE patients.
OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA.
MATERIALS AND METHODS: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention.
RESULTS: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05).
CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.
OBJECTIVE: Nigella sativa is a medicinal plant that has long been used in traditional medicine for treating various conditions. Numerous animal studies provided evidences that the seed may elicit a broad anti-inflammatory/anti-oxidant activity. The aim of the present clinical trial was to evaluate anti-inflammatory and antioxidant properties of Nigella sativa oil in patients with rheumatoid arthritis (RA).
MATERIALS AND METHODS: Forty-two patients with RA were assigned into two groups in this randomized, double blind, placebo-controlled clinical trial. Subjects in intervention group received two capsules, 500 mg each, of Nigella sativa oil, each day for 8 weeks. The other group consumed two capsules as placebo per day for the same period of time. Serum TNF-α, IL-10, and whole blood levels of oxidative stress parameters were measured at baseline and end of the trial.
RESULTS: The serum level of IL-10 was increased in the Nigella sativa group (p<0.01). Moreover, treatment with Nigella sativa led to significant reduction of serum MDA and NO compared with baseline (p<0.05). There were no significant differences in the TNF-α, SOD, catalase, and TAS values between or within the groups, before and after the intervention (p>0.05).
CONCLUSION: This study indicates that Nigella sativa could improve inflammation and reduce oxidative stress in patients with RA. It is suggested that Nigella sativa may be a beneficial adjunct therapy in this population of patients.
BACKGROUND: To evaluate the clinical outcomes of a group of patients affected by knee osteoarthritis (OA) treated with MD-Knee (Guna S.p.a., Milan, Italy) versus a group of patients treated with sodium hyaluronate.
METHOD: This non-inferiority prospective randomized controlled trial involved 60 patients affected by knee OA, grade 2-3 of Kellgren-Lawrence scale. The MD-Knee Group, Group A (n = 29) was administered five intra-articular injections at 1 week interval; the sodium hyaluronate Group, Group B (n = 31), was administered five doses of intra-articular injection of sodium hyaluronate at 1 week interval. All patients were prospectively evaluated before and at 3 and 6 months after the treatment by the Lequesne Knee Index (LKI) as primary endpoint and the Visual Analogue Scale (VAS), Pain Killer consumption and SF-36 questionnaires as secondary endpoints.
RESULTS: At the 3- and 6 month follow-up, LKI and VAS improved significantly in both groups compared to baseline and no statistically significant differences were observed between Group A and Group B. There was no statistically significant difference in the SF36 questionnaire score and pain killer consumption between two groups at any time point.
CONCLUSIONS: This study shows that both preparations exert similar clinical effects as assessed through multiple outcome measures. MD-Knee is effective on knee OA symptoms over 6 months after a 5-weekly injection course, and it is equally effective as the reference sodium hyaluronate.
TRIAL REGISTRATION:
TRIAL REGISTRATION NUMBER: ISRCTN93862496 . Registration date: January 18th, 2016.
Tripterygium wilfordii Hook F. (TwHF) based therapy has been proved as effective in treating rheumatoid arthritis (RA), yet the predictors to its response remains unclear. A two-stage trial was designed to identify and verify the baseline symptomatic predictors of this therapy. 167 patients with active RA were enrolled with a 24-week TwHF based therapy treatment and the symptomatic predictors were identified in an open trial; then in a randomized clinical trial (RCT) for verification, 218 RA patients were enrolled and classified into predictor positive (P+) and predictor negative (P-) group, and were randomly assigned to accept the TwHF based therapy and Methotrexate and Sulfasalazine combination therapy (M) for 24 weeks, respectively. Five predictors were identified (diuresis, excessive sweating, night sweats for positive; and yellow tongue-coating, thermalgia in the joints for negative). In the RCT, The ACR 20 responses were 82.61% in TwHF/P+ group, significantly higher than that in TwHF/P- group (P = 0.0001) and in M&S/P+ group (P < 0.05), but not higher than in M&S/P- group. Similar results were yielded in ACR 50 yet not in ACR 70 response. No significant differences were detected in safety profiles among groups. The identified predictors enable the TwHF based therapy more efficiently in treating RA subpopulations.
OBJECTIVE: To examine the efficacy and safety of Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine (TCM), in patients with knee osteoarthritis (OA).
DESIGN: A multi-site, randomized, double-blind, placebo-controlled phase II dose-escalation clinical trial was conducted. Eligible patients who fulfilled American College of Rheumatology criteria were randomized to receive either HLXL or placebo. Clinical assessments included measurement of knee pain and function with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), patient global assessment (PGA), and knee pain scores every 2 weeks. A Data and Safety Monitoring Board (DSMB) was established to review the data for ensuring the quality of the trial.
RESULTS: In the first stage, 28 participants were randomized to receive either low-dose HLXL-Dan (2400 mg/day) or placebo for 6 weeks. The results showed no statistical difference between the two groups. The study was then re-designed following the recommendation of DSMB. Ninety-two patients were enrolled in the second stage and were randomized to receive either high-dose HLXL-Dan (4000 mg/day for week 1-2, and 5600 mg/day for week 3-8) or placebo for 8 weeks. All outcome assessments showed significant improvements for both groups after 8 weeks but no significant between-group differences. The change (mean ± SD) of WOMAC pain and WOMAC function scores of HLXL and placebo group after 8 weeks were -1.2 ± 1.7 vs -1.4 ± 1.5, and -1.1 ± 1.6 vs -1.3 ± 1.5 respectively. No serious adverse events were reported.
CONCLUSION: Although safe to use, an 8-week treatment of HLXL-Dan was not superior to placebo for reduction in pain or functional improvement in patients with knee OA.
CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT00755326).
PURPOSE: To compare effects of kinesio taping with sham taping at the end of 3 consecutive taping periods in knee osteoarthritis.
METHODS: 41 patients diagnosed with knee osteoarthritis according to American College of Rheumatology were randomized to receive either KT or sham taping. Baseline evaluations included a visual analog scale (VAS) for activity and nocturnal pain, Lequesne index for functional assessment and Nottingham Health Profile (NHP) for the quality of life. Taping was applied every four days, three times, and all of the assessments were repeated at the end of the treatment period.
RESULTS: In both groups VAS for activity pain, VAS for nocturnal pain, Lequesne index score, NHP score decreased significantly. NHP energy scores were different significantly between the groups in favor of sham taping at the end of the 12-day period.
CONCLUSION: Our findings indicate inconclusive evidence of a beneficial effect of kinesio taping over sham taping in knee osteoarthritis.
Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory.
OBJECTIVE:
To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels.
DESIGN, SETTING, AND PARTICIPANTS:
A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013.
INTERVENTIONS:
Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years.
MAIN OUTCOMES AND MEASURES:
Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI).
RESULTS:
Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text].
CONCLUSIONS AND RELEVANCE:
Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis.
