Articles: p38-mitogen-activated-protein-kinases.
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Randomized Controlled Trial Multicenter Study Comparative Study
The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: a multicenter FDG-PET trial.
This study evaluated the effect of p38 mitogen-activated protein kinase (p38MAPK) inhibitor, BMS-582949, on atherosclerotic plaque inflammation, using (18)FDG-PET imaging. p38MAPK is an important element of inflammatory pathways in atherothrombosis and its inhibition may lead to reduced inflammation within atherosclerotic plaques. ⋯ The findings of this study demonstrates that in stable atherosclerosis, 12 weeks of treatment with BMS-582949 did not reduce arterial inflammation or hs-CRP compared to placebo, whereas intensification of statin therapy significantly decreased arterial inflammation.
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American heart journal · May 2015
Randomized Controlled Trial Multicenter Study Comparative StudyRationale and design of the LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic target and moDify outcomes after an acute coronary syndromE trial.
p38 mitogen-activated protein kinase (MAPK) mediates cytokine production and amplification of the inflammatory cascade. Through inhibition of p38 MAPK, losmapimod appears to attenuate the inflammatory response in the vascular wall and thus may help stabilize plaques. ⋯ The LATITUDE-TIMI 60 trial will determine the efficacy and safety of short-term p38 MAPK inhibition with losmapimod in acute MI. The trial design adopts a stepwise approach to decision making and collection of data.
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American heart journal · May 2015
Randomized Controlled Trial Multicenter Study Comparative StudyRationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo.
Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. ⋯ ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk.
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Randomized Controlled Trial Multicenter Study
Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised phase 2 trial.
p38 MAPK inhibition has potential myocardial protective effects. We assessed losmapimod, a potent oral p38 MAPK inhibitor, in patients with non-ST-segment elevation myocardial infarction (NSTEMI) in a double-blind, randomised, placebo-controlled trial. ⋯ GlaxoSmithKline.
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J. Psychopharmacol. (Oxford) · Jun 2014
Randomized Controlled Trial Multicenter StudyEvaluation of antidepressant properties of the p38 MAP kinase inhibitor losmapimod (GW856553) in Major Depressive Disorder: Results from two randomised, placebo-controlled, double-blind, multicentre studies using a Bayesian approach.
Pro-inflammatory cytokines (PICs) may play important pathophysiological roles in some forms of Major Depressive Disorder (MDD). The p38 MAPK inhibitor losmapimod (GW856553) attenuates the pro-inflammatory response in humans by reducing PIC production. Losmapimod (7.5 mg BD) was administered for 6 weeks in two randomised, placebo-controlled trials in subjects with MDD enriched with symptoms of loss of energy/interest and psychomotor retardation (Studies 574 and 009). ⋯ A subsequent study, Study 009 (n=128), designed using a Bayesian approach based on a prior derived from Study 574, showed no advantage for losmapimod (Bech, 6 weeks: endpoint drug vs. placebo difference = 1.11; 95% credible interval, -0.22, 2.50). Biomarker data showed no significant changes. In conclusion 7.5 mg BID losmapimod was not effective in MDD.