scholarly journals CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial

2010 ◽  
Vol 69 (11) ◽  
pp. 2013-2016 ◽  
Author(s):  
Arno W R van Kuijk ◽  
Clarissa E Vergunst ◽  
Danielle M Gerlag ◽  
Barry Bresnihan ◽  
Juan J Gomez-Reino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chemokine Receptor ◽  
Controlled Trial ◽  
Active Treatment Group ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Before And After ◽  
Trial Treatment ◽  
Ccr5 Blockade

ObjectiveC-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects of a CCR5 antagonist in collagen-induced arthritis in rhesus monkeys. The effects of CCR5 blockade in patients with active RA were explored.MethodsIn this phase Ib randomised, placebo-controlled trial, treatment with an oral CCR5 inhibitor (SCH351125) in patients with active RA was evaluated. Clinical efficacy was assessed using European League Against Rheumatism and American College of Rheumatology response criteria. ST biopsies were taken before and after 28 days of treatment, and analysed for CCR5+ cells. In a subset of patients, MRIs of an inflamed joint were obtained before and after treatment.ResultsIn all, 32 patients were included; 20 received SCH351125 and 12 placebo. Three patients who received SCH351125 did not complete the study due to adverse events; none of these were serious. No improvement was observed in the active treatment group compared to placebo. Results were consistent for clinical evaluation, ST analysis and MRI.ConclusionThis proof of concept study does not support the use of CCR5 blockade as a therapeutic strategy in patients with active RA.

scholarly journals Plasma MicroRNA Profiles in Patients with Early Rheumatoid Arthritis Responding to Adalimumab plus Methotrexate vs Methotrexate Alone: A Placebo-controlled Clinical Trial

2017 ◽  
Vol 45 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Jacob Sode ◽  
Sophine B. Krintel ◽  
Anting Liu Carlsen ◽  
Merete L. Hetland ◽  
Julia S. Johansen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Multiple Testing ◽  
Controlled Trial ◽  
Roc Curves ◽  
Predictive Biomarker ◽  
Controlled Clinical Trial ◽  
Operating Characteristics ◽  
American College Of Rheumatology ◽  
Plasma Microrna

Objective.The aim was to identify plasma (i.e., cell-free) microRNA (miRNA) predicting antitumor necrosis and/or methotrexate (MTX) treatment response in patients enrolled in an investigator-initiated, prospective, double-blinded, placebo-controlled trial (The OPERA study,NCT00660647).Methods.We included 180 disease-modifying antirheumatic drug–naive patients with early rheumatoid arthritis (RA) randomized to adalimumab (ADA; n = 89) or placebo (n = 91) in combination with MTX. Plasma samples before and 3 months after treatment initiation were analyzed for 91 specific miRNA by quantitative reverse transcriptase-polymerase chain reaction on microfluidic dynamic arrays. A linear mixed-effects model was used to test for associations between pretreatment miRNA and changes in miRNA expression and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean (28 joints) remission at 3 and 12 months, applying false discovery rate correction for multiple testing. Using leave-one-out cross validation, we built predictive multivariate miRNA models and estimated classification performances using receiver-operating characteristics (ROC) curves.Results.In the ADA group, a higher pretreatment level of miR-27a-3p was significantly associated with remission at 12 months. The level decreased in remitting patients between pretreatment and 3 months, and increased in nonremitting patients. No associations were found in the placebo group receiving only MTX. Two multivariate miRNA models were able to predict response to ADA treatment after 3 and 12 months, with 63% and 82% area under the ROC curves, respectively.Conclusion.We identified miR-27a-3p as a potential predictive biomarker of ACR/EULAR remission in patients with early RA treated with ADA in combination with MTX. We conclude that pretreatment plasma-miRNA profiles may be of predictive value, but the results need confirmation in independent cohorts.

scholarly journals A multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of Huang Qi Gui Zhi Wu Wu Tang granules in patients with rheumatoid arthritis

2018 ◽  
Author(s):  
Yang Liu ◽  
Yi-Ru Wang ◽  
Zhi-jie Xi ◽  
Yang Yu ◽  
Li Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Decision Making ◽  
Controlled Trial ◽  
Rate Of Change ◽  
Secondary Outcome ◽  
Controlled Clinical Trial ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Multicenter Randomized Controlled Trial

Abstract Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by swelling, pain, and synovial damage. Effective methods lack in the treatment of RA. A traditional prescription in use for thousands of years in China, Huang Qi Gui Zhi Wu Wu Tang (HQGZWWT) granule is still chosen to relive pain and prevent joint malformation in RA patients. However, no evidence-based medical research has been organized to assess the effectiveness and safety of HQGZWWT granules for RA. Methods/design: We will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial to determine whether HQGZWWT granules can relieve pain and protect joints. We will randomly divide 120 patients with active arthritis for 3 months. Main measurements include ratio of 50 of ACR (American College of Rheumatology), change of DAS (28) from baseline to 3 months, and SHARP scores of van der Heijde from baseline to 12 months. SecondarymeasurementsincludeACR20, ACR70, Health Assessment Questionnaire-Disability Index (HAQ-DI), arthritis pain score, and Patient Global Assessment of Arthritis. The time points are set as baseline, 2 weeks, 1 month, 2 months, 3 months, 6 months and 12 months. In addition, the rate of change (score) in the ACR50 and DAS28 from the baseline to 2-week, 1-month, 2-month, 6-month, and 12-month follow-up are also the secondary outcome measures. Discussion: The findings of this research will elucidate the efficacy and safety of HQGZWWT granules and provide an alternative treatment for RA. In addition, our data will benefit the clinical decision-making on active RA and possibly be incorporated into future guidelines. Trial registration: ClinicalTrials.gov ID: NCT03593837. Keywords: Traditional Chinese medicine, Huang Qi Gui Zhi wu wu granules, placebo, active rheumatoid arthritis, multicenter, randomized controlled trial.

scholarly journals Fosdagrocorat (PF-04171327) versus prednisone or placebo in rheumatoid arthritis: a randomised, double-blind, multicentre, phase IIb study

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000889 ◽  
Author(s):  
Frank Buttgereit ◽  
Vibeke Strand ◽  
Eun Bong Lee ◽  
Abraham Simon-Campos ◽  
Dorothy McCabe ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Controlled Trial ◽  
Double Blind ◽  
Multicentre Phase ◽  
Procollagen Type ◽  
Mediated Effects ◽  
American College Of Rheumatology ◽  
Primary Endpoints ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesGlucocorticoids have anti-inflammatory, transrepression-mediated effects, although adverse events (AEs; transactivation-mediated effects) limit long-term use in patients with rheumatoid arthritis (RA). We evaluated the efficacy and safety of fosdagrocorat (PF-04171327), a dissociated agonist of the glucocorticoid receptor, versus prednisone or placebo.MethodsIn this 12-week, phase II, randomised controlled trial, 323 patients with moderate to severe RA were randomised 1:1:1:1:1:1:1 to fosdagrocorat (1 mg, 5 mg, 10 mg or 15 mg), prednisone (5 mg or 10 mg) or placebo, once daily. The primary endpoints (week 8) were American College of Rheumatology 20% improvement criteria (ACR20) responses, and percentage changes from baseline in biomarkers of bone formation (procollagen type 1 N-terminal peptide [P1NP]) and resorption (urinary N-telopeptide to urinary creatinine ratio [uNTx:uCr]). Safety was assessed.ResultsACR20 responses with fosdagrocorat 10 mg and 15 mg were superior to placebo, and fosdagrocorat 15 mg was non-inferior to prednisone 10 mg (week 8 model-predicted ACR20 responses: 47%, 61%, 69% and 73% vs 51%, 71% and 37% with fosdagrocorat 1 mg, 5 mg, 10 mg and 15 mg vs prednisone 5 mg, 10 mg and placebo, respectively). Percentage changes from baseline in P1NP with fosdagrocorat 1 mg, 5 mg and 10 mg met non-inferiority criteria to prednisone 5 mg. Corresponding changes in uNTx:uCr varied considerably. All fosdagrocorat doses reduced glycosylated haemoglobin levels. AEs were similar between groups; 63 (19.5%) patients reported treatment-related AEs; 9 (2.8%) patients reported serious AEs. No patients had adrenal insufficiency, treatment-related significant infections or laboratory abnormalities. No deaths were reported.ConclusionIn patients with RA, fosdagrocorat 10 mg and 15 mg demonstrated efficacy similar to prednisone 10 mg and safety similar to prednisone 5 mg.Trial registration numberNCT01393639

scholarly journals Therapeutic Efficacy of Urtica dioica and Evening Primrose in Patients with Rheumatoid Arthritis: A Randomized Double-Blind, Placebo-Controlled Clinical Trial

2021 ◽  
Author(s):  
Bahareh Abd-Nikfarjam ◽  
Mahnaz Abbasi ◽  
Mohammadreza Memarzadeh ◽  
Seyed-Amir Farzam ◽  
Azam Jamshidian ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Placebo Group ◽  
Controlled Trial ◽  
Urtica Dioica ◽  
Inflammatory Factors ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Evening Primrose ◽  
Anti Oxidant

Abstract Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease. The pharmacological therapy of RA is often symptomatic to mitigate pain and inability with analgesics and drugs with defined side effects and risks. Complementary medicines might decrease the signs of RA and reduce the need for these medicines. In the present study, we investigated the anti-rheumatic, anti-inflammatory and anti-oxidant effects of Urtica dioica and Evening Primrose Ogil (EPO), in patients with RA. Methods: This randomized, double‐blind, controlled trial involved 90 RA patients, and randomly assigned them into EPO, Urtica dioica, and placebo groups. The potential effect of these herbal medicines on Disease Activity Score (DAS) 28, Visual Analogue Scale (VAS), Total Anti-oxidant Capacity (TAC), IL-17, Rheumatoid Factor (RF), anti-cyclic citrullinated peptide antibodies (Anti-CCP), C Reactive Protein (CRP), and Erythrocyte Sedimentation Rate (ESR) before and after clinical trial were evaluated. The trial registration number is IRCT20201001048897N1.Results: After a three month follow up, the mean values of DAS28, IL-17, TAC, RF, and CRP in EPO and Urtica dioica groups were significantly different from the placebo group. However, the VAS, Anti-CCP, and ESR at baseline and at the end of the study were not significantly different between the three groups. After the intervention, the within-group DAS28 in the EPO and Urtica dioica groups, and placebo group reduced significantly compared to the baseline.Conclusion: Medicinal plants EPO and Urtica dioica were appeared to decrease inflammatory factors, and can improve the symptoms of RA. Thus, EPO and Urtica dioica have great potential as a complementary therapy in RA patients.

Vitamin D3 reduces risk of cardiovascular and liver diseases by lowering homocysteine levels: double-blinded, randomised, placebo-controlled trial

2020 ◽  
Vol 125 (2) ◽  
pp. 139-146
Author(s):  
N. Al-Bayyari ◽  
R. Hailat ◽  
H. Subih ◽  
H. Alkhalidy ◽  
A. Eaton
Keyword(s):  
Vitamin D ◽  
Kidney Function ◽  
Liver Diseases ◽  
Controlled Trial ◽  
Liver Function Tests ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Overweight Women ◽  
Function Tests ◽  
Before And After

AbstractThe objective of this study was to evaluate the effect of vitamin D3 on total homocysteine (tHcy) and C-reactive protein (CRP) levels and liver and kidney function tests in overweight women with vitamin D deficiency. Therefore, a randomised, double-blind placebo, controlled clinical trial was conducted on 100 eligible women. Subjects were randomly divided into two groups: the placebo (n 50) and the vitamin D (n 50) which received 1250 µg vitamin D3 per week for 2 months. The participants’ 25-hydroxyvitamin D (25(OH)D), tHcy, CRP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and estimated glomerular filtration rate (eGFR) were measured and compared before and after treatment. Results showed that the tHcy, CRP, AST, ALT and eGFR levels after the 2nd month of vitamin D3 intervention were significantly (P < 0·001) decreased and the 25(OH)D, urea and creatinine levels were significantly (P < 0·001) increased in the treatment group. In the placebo group, no significant changes were identified throughout the follow-up period. In conclusion, vitamin D3 intervention with a treatment dose of 1250 µg/week for at least 2 months may help in lowering Hcy and CRP levels and may improve liver function tests, which in turn might help in minimising the risk of CVD and liver diseases among overweight women but negatively affect kidney function.

Frühgeborene unter maschineller Beatmung: Immunmodulatorischer Effekt der präventiven Gabe von Azithromycin

2020 ◽  
pp. 1-3
Author(s):  
Maximilian Jorczyk
Keyword(s):  
Very Low Birth Weight ◽  
Controlled Trial ◽  
Preterm Neonates ◽  
Double Blind ◽  
Mechanically Ventilated ◽  
Before And After ◽  
Anti Inflammatory ◽  
To Receive ◽  
Therapeutic Possibilities ◽  
Inflammatory Effect

<b>Introduction:</b> Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. <b>Objective:</b> The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. <b>Methods:</b> This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for <i>Ureaplasma</i>. Patients were followed up throughout the hospital stay for the outcomes of death and bronchopulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). <b>Results:</b> Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O<sub>2</sub> dependency at 28 days/death in azithromycin-treated patients regardless of the detection of <i>Ureaplasma</i> in blood. <b>Conclusions:</b> Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O<sub>2</sub> dependency at 28 days/death in mechanically ventilated preterm neonates.

scholarly journals Atorvastatin is unlikely to prevent rheumatoid arthritis in high risk individuals: results from the prematurely stopped STAtins to Prevent Rheumatoid Arthritis (STAPRA) trial

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001591
Author(s):  
Laurette van Boheemen ◽  
Samina Turk ◽  
Marian van Beers-Tas ◽  
Wouter Bos ◽  
Diane Marsman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Risk ◽  
Cox Regression ◽  
Controlled Trial ◽  
Pharmacological Intervention ◽  
Trial Participation ◽  
Double Blind ◽  
Cox Regression Analysis ◽  
Atorvastatin Group ◽  
Clinical Arthritis

ObjectivesPersons at high risk of rheumatoid arthritis (RA) might benefit from a low-risk pharmacological intervention aimed at primary prevention. Previous studies demonstrated disease-modifying effects of statins in patients with RA as well as an association between statin use and a decreased risk of RA development. A randomised, double-blind, placebo-controlled trial investigated whether atorvastatin could prevent arthritis development in high-risk individuals.MethodsArthralgia patients with anticitrullinated protein antibody (ACPA) >3 xULN or ACPA and rheumatoid factor, without (a history of) arthritis, were randomised to receive atorvastatin 40 mg daily or placebo for 3 years. The calculated sample size was 220 participants. The primary endpoint was clinical arthritis. Cox regression analysis was used to determine the effect of atorvastatin on arthritis development.ResultsDue to a low inclusion rate, mainly because of an unwillingness to participate, the trial was prematurely stopped. Data of the 62 randomised individuals were analysed. Median follow-up was 14 (inner quartiles 6–35) months. Fifteen individuals (24%) developed arthritis: 9/31 (29%) in the atorvastatin group; 6/31 (19%) in the placebo group: HR 1.40, 95% CI 0.50 to 3.95.ConclusionsIn this small set of randomised high-risk individuals, we did not demonstrate a protective effect of atorvastatin on arthritis development. The main reason for the low inclusion was unwillingness to participate; this may also impede other RA prevention trials. Further research to investigate and solve barriers for prevention trial participation is needed.

scholarly journals Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aziza Ajlan ◽  
Hassan Aleid ◽  
Tariq Zulfiquar Ali ◽  
Hala Joharji ◽  
Khalid Almeshari ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Controlled Trial ◽  
Controlled Clinical Trial ◽  
First Year ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Double Blind ◽  
Donor Specific Antibodies

Abstract Background Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. Aims To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. Methods Prospective, randomized, double blind, non-inferiority, controlled clinical trial Expected outcomes 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. Secondary outcomes: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) Trial registration The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.

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