A double blind, randomised, placebo-controlled trial to evaluate the efficacy of metformin to treat preterm pre-eclampsia (PI2 Trial): study protocol

INTRODUCTION:Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far more fetal losses. There is no definitive treatment other than delivery. A therapeutic that could quench the disease process would be useful to treat preterm pre-eclampsia, as it could allow these pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have published preclinical data to show that metformin, a drug known to be safe in pregnancy and commonly used to treat gestational diabetes, has potent biological effects making it another promising candidate to treat pre-eclampsia. Here, we describe a phase II clinical trial to examine whether administering extended-release metformin may be effective in treating women with preterm pre-eclampsia (PI2 Trial). METHODS:The PI2 Trial is a phase II, double blind, randomised controlled trial that aims to recruit 150 women with preterm pre-eclampsia (gestational age 26+0 to 31+6 weeks) who are being managed expectantly. Participants will be randomised to receive either 3 g of metformin or placebo daily. The primary outcome is time from randomisation until delivery. A delay in delivery of 5 days is assumed to be clinically relevant. The secondary outcomes will be a maternal composite and neonatal composite outcome. All other outcomes will be exploratory. We will record adverse events. ETHICS AND DISSEMINATION:This study has ethical approval (Protocol number M16/09/037 Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), is registered with the Pan African Clinical Trial Registry (PACTR201608001752102) and the South African Medicine Control Council (20170322). Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:PACTR201608001752102; Pre-results.Catherine Cluver, Susan P Walker, Ben W Mol, David Hall, Richard Hiscock, Fiona C Brownfoot, Tu’uhevaha J Kaitu’u-Lino, Stephen Ton

Influence of the photopolymerization matrix on the indicator response of optical fiber pH sensors

Optical fiber pH sensors work by observing a change in the indicator’s optical signal caused by variations in pH and these indicators can be immobilized onto the surface of an optical fiber using a polymer matrix. How the composition of the polymer matrix changes pH detection range using the indicator (5(6)-carboxynaphthofluorescein (CNF)) has not been studied. Here we show that the composition of the polymer matrix affects the working pH ranges of optical fiber CNF sensors. We used acrylamide (AAm) or N-isopropylacrylamide (NIPAM) as the backbone monomer, and N, N’-methylenebisacrylamide (BIS) as the crosslinker for the polymer matrix. We found that AAm-based pH sensors showed rapid response over the pH range 6.6 – 8.0, while the dynamic ranges of NIPAM-based sensors shifted to basic pH compared with AAm-based pH sensors. Furthermore, we found that an increased ratio of the backbone monomer, NIPAM, over the crosslinker, BIS, significantly shifted the working range to more basic pH values, covering a pH range of 8.1 – 10.3. Our results demonstrate that the polymer matrix can be a powerful means to control the indicator response of optical pH sensors.Kwang Jun Lee, Patrick K. Capon, Heike Ebendorff-Heidepriem, Emerson Keenan, Fiona Brownfoot, Erik P. Schartne