Ursodeoxycholic Acid vs Metformin in Gestational Diabetes Mellitus

• Status: Not yet recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: Female

Summary

GUARD is a Clinical Trial that wants to explore the impact of UDCA compared to metformin in the treatment of GDM. The trial wants to recruit 158 women who are overweight or obese who have been diagnosed with GDM, and require pharmacological treatment. Glucose control is our primary measure.

Each year in the UK approximately 35,000 women develop diabetes during pregnancy, a condition called gestational diabetes mellitus (GDM), which increases the risk of adverse outcomes for both mother and child. Metformin, although unlicensed for used in pregnancy, is the most commonly used first line pharmacological treatment. However, there is increasing concern about its widespread use during pregnancy, because of its limited efficacy and because of potential safety concerns. Other common treatments have not been shown to be superior. Therefore, there is an unmet need for additional therapies.

Ursodeoxycholic acid (UDCA) is commonly used in pregnancy for the treatment of intrahepatic cholestasis of pregnancy. It is currently not an established/licensed treatment for GDM. However data from observational studies of women with cholestasis in pregnancy has flagged this to be a potential effective treatment to control blood glucose levels in GDM.

The investigators will ask women to attend three study visits, which will coincide with the time of their antenatal appointments. The trial aims to collect a range of clinical and research blood samples, to measure quality of life and treatment satisfaction through two questionnaires, and will will ask women to wear a continuous glucose monitor for three 10 day periods.

There will be a number of optional assessments that participants will be offered. The primary outcome will be the fasting blood glucose concentration at 36 weeks of gestation.

The investigators intend to carry out this study at 3 sites in the United Kingdom (Guy's and St Thomas, Imperial College and Nottingham), and it has been funded by a J.P Moulton Foundation grant.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: King's College London
• Collaborator: Guy's and St Thomas' NHS Foundation Trust
• Treatments: Metformin; Ursodeoxycholic Acid

Criteria

Inclusion Criteria:

1. Women between 16 and 45 years of age with GDM diagnosed at 26+0 to 30+6 weeks' gestation in accordance with the NICE guidelines (one or more glucose concentrations of ≥5.6 mmol/l fasting or ≥7.8 mmol/l 2 hours after a standard 75g OGTT, and requiring pharmacological treatment).

2. Overweight or obese (Booking BMI ≥25 kg/m2)

3. Planned antenatal, intrapartum and postpartum care at the participating centre (i.e. not planning to move before delivery).

Exclusion Criteria:

1. Unwilling/unable to give written informed consent and comply with the requirements of the study protocol

2. Multiple pregnancies (twins, triplets etc) in current pregnancy

3. Congenital anomaly on ultrasound requiring fetal medicine input

4. Previous diagnosis of diabetes outside pregnancy

5. HbA1c at booking >48 mmol/mol or ≥6.5% during current pregnancy (if available)

6. Significant pre-pregnancy comorbidities that increase risk in pregnancy, for example renal failure, severe liver disease, transplantation, cardiac failure, psychiatric conditions requiring in-patient admission (within previous year) in the opinion of the responsible clinician or the CI.

7. Significant co-morbidity in the current pregnancy, nephropathy (estimated GFR <60ml/min), other physical or psychological conditions likely to interfere with the conduct of the study and/or interpretation of the trial results in the opinion of the responsible clinician or the CI.

8. Not fluent in English and absence of interpreter or translation services (ie telephone translation services)

9. Participating in another intervention study where the results could influence GDM-related endpoints, in the opinion of the responsible clinician or the CI, or participation in a CTIMP during current pregnancy.

10. Known allergy/hypersensitivity/intolerance to the active substance or excipients, or patients taking any medications which are contraindicated as per IMP SmPC