Closed-loop insulin delivery in pregnant women with type 1 diabetes (the CRISTAL study)
Type 1 diabetes (T1DM) during pregnancy is associated with increased risk of maternal and neonatal complications such as pre-eclampsia, preterm delivery, caesarean sections, congenital malformations and perinatal mortality. Even with increasing use of new continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII, insulin pumps) technologies, pregnant women with T1DM continue to spend on average 8 hours/day hyperglycaemic. We hypothesize that the 780G system with a glucose target at 100 mg/dL in pregnant women with T1DM can improve glycaemic control with less hypoglycaemia. This in turn, might improve pregnancy outcomes in women with T1DM. The CRISTAL study is a Belgian open-label RCT in pregnant women with T1DM to assess safety, efficacy, feasibility and cost-effectiveness of the day-and-night closed-loop 780G system compared to usual standard of care therapy. Women will be offered inclusion in the study in pregnancy up to 12 weeks. Participants will be randomized 1/1 to either the 780G system (intervention group) or the usual standard of care group (control group). Differences in glycaemic control between both groups will be evaluated by using the (masked) CGM at different time points during pregnancy (8-11 weeks, 14-17 weeks, 22-25 weeks, 30-33 weeks and 36-39 weeks) for three weeks. The study ends after the hospital stay at delivery. The primary endpoint is the percentage of time spent within the T1DM pregnancy target range (TIR 63–140 mg/dL) as measured by the CGM. Prespecified secondary endpoints derived from CGM measures are time in range (TIR) during the night (period from after evening meal till before breakfast), time spent below low day and night (<63 mg/dL) and overnight time <63 mg/dL. In total, 92 participants will be included to have at least 90 % power to detect a between group difference in mean TIR (63-140 mg/dL) of 10 % during pregnancy, assuming a 20 % loss to follow-up during the study. In line with normal routine, participants will be followed-up every two weeks during pregnancy at the out-patient diabetes clinic. At time of (masked) CGM during pregnancy, additional blood samples will be taken for central analysis of HbA1c and to store at the biobank of UZ Leuven for future analyses of novel biomarkers. At these time points, participants of both groups will be asked to complete different questionnaires. In addition, clinical examination is in line with normal routine follow-up (measurement of weight and blood pressure).