A multi-centre phase IIa clinical study of predictive testing for preeclampsia: improved pregnancy outcomes via early detection (IMPROvED)

Abstract

Background5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia.Methods/DesignWe report the design of a multicentre, phase IIa clinical study aiming to recruit 5000 low risk primiparous women to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves maternal phlebotomy at 15 and 20 weeks’ gestation, with optional testing and biobanking at 11 and 34 weeks. Blood samples will be analysed using two innovative, proprietary prototype platforms; one metabolomic based and one proteomic based, both of which outperform current biomarker based screening tests at comparable gestations. Analytical and clinical data will be collated and analysed via the Copenhagen Trials Unit.DiscussionThe IMPROvED study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If ‘at risk’ patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROvED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome.Trial registrationTrial registration number NCT01891240The IMPROvED project is funded by the seventh framework programme for Research and Technological development of the EU. http://www.fp7-improved.eu/

Applications of metabolomics in the study and management of preeclampsia: a review of the literature

“…The largest studies contained a total of 167 cases (Koster, Vreeken, Harms, Dane, Kuc, Schielen, Hankemeier et al 2015; Kuc, Koster, Pennings, Hankemeier, Berger, Harms, Dane et al 2014), and interestingly although these studies identified serum steroylcarnitine and taurine as potential predictive biomarkers they concluded at present metabolomics-based assays are not suitable for preeclampsia. Larger studies such as the ongoing multi-center IMPROvED (improved pregnancy outcomes via early detection) (Navaratnam, Alfirevic, Baker, Gluud, Grüttner, Kublickiene, Zeeman et al 2013) study, which aims to recruit 5000 pregnant women in order to develop predictive metabolomic and proteomic signatures of preeclampsia, are required.…”

“…Novel approaches are required for the study, prediction, diagnosis, classification, management and treatment of this condition (Navaratnam, Alfirevic, Baker, Gluud, Grüttner, Kublickiene, Zeeman et al 2013). …”

Risk factors and effective management of preeclampsia

“…A recent profiling study, utilizing multivariate predictive modeling combining 14 metabolites, gave an odds ratio for developing preeclampsia of 36 (95% CI: 12–108), with an area under the receiver operator characteristic curve of 0.94 33. A Phase IIa clinical study is planned to further investigate these emerging metabolomic technologies 34. Another recent study has demonstrated characteristic proteomic biomarkers in the urine of women.…”

From Glomerular Endothelium to Podocyte Pathobiology in Preeclampsia: a Paradigm Shift

“…Personalized medicine is defined as a strategy that seeks to improve stratification and timing of health care by utilizing biological information and biomarkers at the level of molecular disease pathways, genetics, proteomics, and metabolomics [82]. Recently, tests using both proteomics and metabolomics for the prediction and early detection of preeclampsia were developed [83,84], and a multicenter trial is ongoing to assess their clinical applicability [85]. However, these tests do not involve specific markers for renal involvement in preeclampsia.…”