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A multi-centered trial investigating gestational treatment with ursodeoxycholic acid compared to metformin to reduce effects of diabetes mellitus (GUARD): a randomized controlled trial protocol

Research output: Contribution to journalArticlepeer-review

Holly Lovell, Alice Mitchell, Caroline Ovadia, Noelia Pitrelli, Annette Briley, Claire Singh, Hanns-Ulrich Marschall, Kennedy Cruickshank, Helen Murphy, Paul Seed, Catherine Williamson

Original languageEnglish
Article number571
Number of pages21
JournalTrials
Volume23
Issue number1
DOIs
Accepted/In press9 Jun 2022
Published19 Jul 2022

Bibliographical note

Funding Information: Funding to conduct the trial is provided by J.P. Moulton Foundation (REF Tommy’s Grant 81) and an NIHR Senior Investigators grant (Professor Catherine Williamson). Publisher Copyright: © 2022, The Author(s).

King's Authors

Abstract

BACKGROUND: Each year in the UK, approximately 35,000 women develop gestational diabetes mellitus (GDM). The condition increases the risk of obstetric and neonatal complications for mother and child, including preeclampsia, preterm birth, and large for gestational age babies. Biochemical consequences include maternal hyperglycemia, neonatal hypoglycemia, and dyslipidemia. Metformin is the most commonly used firstline pharmacological treatment. However, there are concerns about its widespread use during pregnancy, due to its limited efficacy and potential safety concerns. Therefore, there is a need for additional therapies that improve both maternal-fetal glucose and lipid metabolism. Ursodeoxycholic acid (UDCA) is not currently used for treatment for GDM. However, it can improve glucose control in type 2 diabetes, and it improves fetal lipid profiles in gestational cholestasis. Consequentially, it is hypothesized that treatment with UDCA for women with GDM may improve both maternal metabolism and neonatal outcomes. The primary outcome of this trial is to assess the efficacy of UDCA compared with metformin to improve glucose levels in women with GDM.

METHODS: The trial is a two-armed, open-label, multi-center, randomized controlled trial. Women are eligible if they have been diagnosed with GDM by an oral glucose tolerance test between 24 + 0 and 30 + 6 weeks' gestation, and if they require pharmacological intervention. In total, 158 pregnant women will be recruited across seven NHS Trusts in England and Wales. Women who consent will be recruited and randomized to either metformin or UDCA, which will be taken daily until the birth of their baby. Maternal and neonatal blood samples will be taken to evaluate the impact of the treatments on maternal glucose control, and maternal and neonatal lipid metabolism. Maternal and fetal outcomes will be evaluated, and acceptability of UDCA compared with metformin will be assessed.

DISCUSSION: This trial has the potential to identify a potential new treatment for women with GDM. If successful, a future large multi-center trial will be designed to investigate where decisions can be personalized to identify which women will respond more effectively to UDCA than alternatives to improve maternal and baby outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04407650.

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