Gyulai R.,University of Szeged |
Gyulai R.,University of Pecs |
Bagot M.,Saint Louis Hospital |
Griffiths C.E.M.,University of Manchester |
And 5 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2015
Background: Methotrexate is one the most commonly used systemic therapies for psoriasis. Despite its widespread use in psoriasis therapy, dermatologists' practice regarding the use of methotrexate has not been investigated on global scale. Objective: To evaluate the real life use of methotrexate for psoriasis treatment in the dermatological community worldwide. Methods: A questionnaire consisting of 41 questions was designed by the Psoriasis International Network (PIN). Questions focused on safety, dosing, administration, folic acid supplementation and combination therapy aspects of methotrexate use. The anonymous web-based survey was distributed to dermatologists by the national coordinators of PIN. Results: Between 2 April and 7 August 2012, 481 dermatologists from 63 countries completed the questionnaire. Most respondents were from European and South American countries, whereas the response rate from Central America and the Near East was lowest. The majority of responders were experienced dermatologists (86% had more than 5 years of experience in psoriasis treatment). Starting and maintenance doses of 10 mg of methotrexate or lower were reported by 67% and 42% of respondents respectively. Thirty-eight per cent of respondents stop treatment at a cumulative dose of 2 g, whereas 36% did not consider cumulative dose important in this respect. The primary mode of administration was oral, and the majority of respondents administer folic acid supplementation. Almost all respondents monitored full blood count, liver and renal function tests, whereas procollagen 3 amino terminal peptide measurement and transient elastography is used by only a minority of dermatologists. There were significant differences concerning the doses, routes of administration and safety monitoring among the clinical practices in different geographical locations. Conclusion: Current clinical practice of methotrexate use in psoriasis is not uniform, depends on geographical location, and is not in full agreement with clinical guidelines. © 2014 European Academy of Dermatology and Venereology. Source
BETA3_LVH - A multi-center randomized, placebo-controlled trial of mirabegron, a new beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 5.43M | Year: 2015
Patients with cardiovascular risk factors, e.g. hypertension and obesity are at risk of developing heart failure with preserved ejection fraction (HFpEF), a highly prevalent disease in the elderly, mostly women population. There is currently no specific, defined treatment for HFpEF, beyond control of risk factors. Activation of cardiac and vascular Beta3-adrenergic receptors (B3AR) represents a new concept and a novel target for structural cardiac disease. B3AR expression and coupling were demonstrated in human myocardium and vasculature. In pre-clinical models with expression of the human receptor, its activation attenuates myocardial remodelling, i.e. decreases hypertrophy and fibrosis in response to neurohormonal or hemodynamic stress. Mirabegron is a new agonist of B3AR available for human use, that was recently introduced for a non-cardiovascular indication (overactive bladder disease). The primary objective of the project is to design and implement a multi-centric, prospective, randomized, placebo-controlled clinical trial testing the additional beneficial effect of mirabegron, versus placebo over 12 months on top of standard treatment of patients carrying structural cardiac disease without overt heart failure (stage B of AHA classification); the co-primary end-point will be the quantitative change in myocardial hypertrophy measured by cardiac MRI; and in diastolic ventricular function, measured by Doppler echocardiography (E/E); in addition, exercise tolerance (peak VO2) will be measured as well as circulating biomarkers reflecting both myocardial remodeling and function. In addition, we will test the effect of mirabegron on beige/brown fat activation and metabolism. Our proposal therefore combines a major conceptual advance and repurposing of an original drug to validate pre-clinical discoveries in the context of a major health problem.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 5.99M | Year: 2015
Type 2 diabetes will affect >500 million adults by 2040 and its secondary complications will generate enormous socioeconomic costs - in particular, diabetic kidney disease (DKD), which is already the most common cause of chronic kidney disease. DKD is associated with greatly increased mortality and frequently progresses to end stage renal failure. Pharmacotherapy, dialysis and transplantation represent the mainstay treatments for DKD but are costly and provide only limited protection against adverse outcomes. Mesenchymal Stromal Cell (MSC) therapy is a promising approach to halting the progression of DKD toward end-stage renal failure and may also have ancillary benefits in Type 2 diabetes. In preliminary research, we have demonstrated that a single dose of MSC simultaneously improves kidney function (glomerular filtration rate and albuminuria) as well as hyperglycaemia in animals with DKD. NEPHSTROM will conduct a multi-centre, placebo-controlled clinical trial of a novel MSC therapy for stabilization of progressive DKD, leading to superior clinical outcomes and long-term socioeconomic benefit. A key enabler for this trial is a novel MSC population (CD362\MSC, trade name Cyndacel-M) which delivers higher purity and improved characterisation compared to conventional plastic-adherent MSC. The NEPHSTROM Phase 1b/2a clinical trial will investigate the safety, tolerability and preliminary efficacy of a single intravenous infusion of allogeneic Cyndacel-M versus placebo in adults with progressive DKD. NEPHSTROM investigators will also determine the bio-distribution, mechanisms of action, immunological effects and economic impacts associated with Cyndacel-M therapy for DKD. This research will critically inform the optimal design of subsequent Phase 3 trials of Cyndacel-M. Stabilising progressive DKD through NEPHSTROMs next-generation MSC therapy will reduce the high all-cause mortality and end-stage renal failure risk in people with this chronic non-communicable disease.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.4-3 | Award Amount: 9.64M | Year: 2012
Chronic kidney disease (CKD) affects 8% of the European population and ultimately results in renal failure due to progressive fibrosis. CDK carries a high mortality risk and the number of affected people rises, increasing the demand on renal replacement therapies while the number of available donor organs stays stable. The STELLAR consortium proposes to develop an alternative to renal replacement therapy, based on the repair capacity of newly discovered kidney mesenchymal stromal cells (kMSCs). By injecting kMSC into affected kidneys, we expect to stop kidney fibrosis and induce tissue repair, ultimately leading to the restoration of normal kidney function. The STELLAR consortium will develop protocols for up scalable, high quality isolation of kMSCs and precisely characterize kMSC function in comparison to other MSCs. test kMSCs in several murine renal disease models, to study their effects on fibrosis and tissue repair. discover mechanisms of kidney repair. invest in developing the technology necessary for up scaled isolation and quality control. The STELLAR consortium combines Australian experts on kMSC isolation and characterisation with European experts on renal failure and compounds the state-of-the-art knowledge, facilities and experience needed to develop and validate this novel form of renal therapy. The inclusion of experienced SMEs, with great technical and scientific know-how about assay and protocol development, further strengthens the consortium and will ensure not only the inclusion of new technology, but also a quick translation from bench to clinical application. In conclusion, the STELLAR consortium is capable of developing and pre clinical validation of this new cellular therapy for CDK, based on a new understanding of stromal cells and fibroblast function, while also providing the technology required for rapid, large scale application of the therapy after clinical validation.
Naldi L.,Azienda Ospedaliera Papa Giovanni XXIII |
Naldi L.,Centro Studi
British Journal of Dermatology | Year: 2016
Intangible and institutional conflicts of interest can particularly affect academia. Academic scientists have peculiar social responsibilities with respect to education and research. These responsibilities may conflict with the increased presence of industry in academia and commercialization of academic research through patents and royalties. Drug approval is almost entirely dependent worldwide on data produced in studies led by pharmaceutical industries. A reflection of the increasing role of the market in academic research is given by exaggerated claims in press releases by academic institutions. In consideration of the extensive presence of industry in academia, there is a need for a move from individual to institutional conflicts of interest disclosure, defining institutional policies for regulating conflicts of interest and developing an 'ethically credible partnership'. © 2016 British Association of Dermatologists. Source