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Large-scale Clinical Trials (large-scale + clinical_trials)
Selected AbstractsMetabolic memory in diabetes,focus on insulinDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005Derek LeRoith Abstract Large-scale clinical trials have demonstrated that metabolic control achieved early in the course of diabetes substantially reduces development and progression of diabetes and the associated microvascular complications. Additionally, prospective observational studies have demonstrated that atherogenic and inflammatory mediators are elevated even prior to the onset of diabetes and significantly contribute to subsequent development of macrovascular complications. Collectively, these data suggest that metabolic memories are stored early in the course of diabetes. We believe that insulin suppresses inflammation and also suppresses glucotoxicity and lipotoxicity (and the consequences thereof, such as the formation of advanced glycation end products and epigenetic phenomena), and thus has a pivotal and beneficial role. Comprehensive metabolic control, especially when instituted early, may alter the natural history of diabetic complications by affecting this metabolic memory. Thus, our overall goal is to understand in more detail the molecular mechanisms involved in these changes, thereby affording us opportunities to reduce the long-term effects of diabetes. Copyright © 2005 John Wiley & Sons, Ltd. [source] Optimizing Antiplatelet Therapy in Coronary InterventionsCLINICAL CARDIOLOGY, Issue S6 2000S. B. King III M.D. Abstract Percutaneous coronary intervention has had a dramatic impact on the current practice of cardiology. One of its important limitations, however, is the potential for producing unfavorable outcomes such as acute coronary closure following angioplasty or atherectomy or subacute thrombosis following stent implantation. These complications may lead to death, myocardial infarction, or the need for urgent bypass surgery. One mechanism underlying these clinical events is platelet-mediated thrombosis due to arterial trauma. Therapeutically, platelet activation by thromboxane and adenosine diphosphate (ADP), as well as platelet aggregation by glycoprotein IIb/IIIa (GPIIb/IIIa) receptors, has been inhibited with various pharmacologic agents. c7E3 (abciximab), a monoclonal antibody directed against GPIIb/IIIa, has been shown to have potent effects on reducing both acute and subacute complications. Other parenteral GPIIb/IIIa inhibitors, including peptide and small nonpepude molecules, have also been found to be clinically effective. Oral versions of similar drugs are currently being evaluated, but several have resulted in disappointing efficacy and safety profiles and have failed to show advantages over aspirin. With all antiplatelet agents, in particular GPIIb/IIIa receptor inhibitors, bleeding and vascular complications must be addressed. Inhibition of thromboxane-induced platelet activation with aspirin has been standard therapy for angioplasty and in the global management of vascular disease. Newer agents that block ADP-mediated platelet activation, the thienopyridines, have been found to be synergistic to aspirin in their effects on the complications of coronary intervention. Ticlopidine and, more recently, clopidogrel, in conjunction with aspirin, have become standard therapies for preventing subacute thrombosis after stent implantation. Large-scale clinical trials are ongoing to optimize their use in combination with GPIIb/IIIa inhibitors. [source] A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTS,NEUROUROLOGY AND URODYNAMICS, Issue 4 2007Alan D. Edgar Abstract Despite an unremitting increase in the number of patients presenting symptoms of benign prostate hyperplasia (BPH), the viable treatment options remain relatively limited when compared to other disorders of aging. This has spurred an interest in so-called alternative medicines, many of which continue to be used in spite of the more recent emergence of rationally targeted therapies. Nonetheless, in the case of plant extracts, the vast majority of these have not been subjected to the same rigorous pre-clinical pharmacological testing and large-scale clinical trials now required by health authorities. Furthermore, demonstration of their clinical efficacy in BPH has been hindered by trials of limited duration with a high placebo response. Beginning with a preliminary demonstration of in vitro inhibition of growth factor-mediated fibroblast proliferation with Pygeum africanum extract, a detailed series of in vitro and in vivo studies on prostate growth and bladder function were undertaken. These studies, reviewed herein, have permitted the identification of putative molecular targets of Pygeum africanum extract affecting both growth factor-mediated prostate growth as well as specific parameters of bladder function. These results, corroborated in part by short-term clinical efficacy, set the stage for a large-scale clinical trial to investigate the efficacy of Pygeum africanum extract in the treatment of lower urinary tract symptoms. Neurourol. Urodynam. 26:458,463, 2007. © 2007 Wiley-Liss, Inc. [source] Using Cochrane reviews for oral diseasesORAL DISEASES, Issue 7 2010HV Worthington Oral Diseases (2010) 16, 592,596 Objectives:, To provide readers with information about the Cochrane Oral Health Group and how the reviews on oral diseases have contributed to guideline developments and the commissioning of trials. Materials and methods:, Examples have been selected from the reviews published on The Cochrane Library. Descriptions are given of how these reviews have been used in guideline development and commissioning of trials. Readers are updated on reviews focused on the management of oral cancer and the new venture of diagnostic test reviews. Results:, Reviews on the management of oral diseases due to cancer treatments have been included in guidelines and changed practice in the UK. Cochrane reviews on Bell's Palsy have led to a randomised controlled trial which has changed the evidence base. The Cochrane review on recall intervals between routine appointments has input into the NICE guideline and resulted in a randomised controlled trial to look at different intervals including a risk-based interval. Conclusion:, We hope this article will give readers information on the work of the Cochrane Oral Health Group and insight into the diversity of reviews in oral diseases. The reviews are successfully being used to change practice and as background for the funding of large-scale clinical trials. [source] Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy,ANNALS OF NEUROLOGY, Issue 2 2009Haruhiko Banno MD Objective Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). Animal studies have shown that the pathogenesis of SBMA is dependent on serum testosterone level. This study is aimed at evaluating the efficacy and safety of androgen deprivation by leuprorelin acetate in patients with SBMA. Methods Fifty SBMA patients underwent subcutaneous injections of leuprorelin acetate or placebo in a randomized, placebo-controlled trial for 48 weeks, followed by an open-label trial for an additional 96 weeks, in which 19 patients of the leuprorelin group and 15 of the placebo group received leuprorelin acetate. The patients who did not participate in the open-label trial were also followed up for the 96-week period (UMIN000000474). Results Leuprorelin acetate significantly extended the duration of cricopharyngeal opening in videofluorography and decreased mutant AR accumulation in scrotal skin biopsy. The patients treated with leuprorelin acetate for 144 weeks exhibited significantly greater functional scores and better swallowing parameters than those who received placebo. Autopsy of one patient who received leuprorelin acetate for 118 weeks suggested that androgen deprivation inhibits the nuclear accumulation or stabilization, or both, of mutant AR in the motor neurons of the spinal cord and brainstem. Interpretation These observations suggest that administration of leuprorelin acetate suppresses the deterioration of neuromuscular impairment in SBMA by inhibiting the toxic accumulation of mutant AR. The results of this phase 2 trial support the start of large-scale clinical trials of androgen deprivation for SBMA. Ann Neurol 2009;65:140,150 [source] Clinical trial experience around the globe: Focus on calcium-channel blockersCLINICAL CARDIOLOGY, Issue S2 2003William B. White M.D. Abstract Although certain classes of drugs appear to possess benefits apart from their blood-pressure lowering capability, reduction of blood pressure remains the single most important action of antihypertensive therapy. Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertension therapy. This is especially true for the prevention of stroke in hypertensive patients as evidenced from the Systolic Hypertension in Europe (Syst-Eur) and Systolic Hypertension in China (Syst-China) trials with a long acting dihydropyridine CCB. The same can be said for beta blockers in patients post myocardial infarction. However, most recent clinical trials have underscored the necessity of multiple drug therapy to achieve the goals of blood pressure reduction coupled with outcomes reduction. For example, the many recent large-scale clinical trials have required an average of three or more agents to achieve goal. Thus, the paradigm for hypertension management has been altered to determine the best treatment regimen rather than the best initial agent. While response rates to individual agents across a wide spectrum of patients vary little, not all drugs are equally suited as companion products. In this article, we discuss the most recent outcome trials with the long acting CCBs alone or in combination with other drugs. The evidence shows that calcium antagonists remain an important part of hypertension management, including in those individuals at risk of cardiac and cerebrovascular events. [source] | ||||||||||