Comparison of Ursodeoxycholic Acid to Metformin to treat women with Gestational Diabetes Mellitus.

Randomised controlled trial of Gestational treatment with Ursodeoxycholic Acid compared to Metformin to Reduce effects of Diabetes mellitus - GUARD

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-002880-82-GB

Enrollment

158

Registered

2020-06-02

Start date

2020-05-05

Completion date

Unknown

Last updated

2020-12-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gestational Diabetes Mellitus MedDRA version: 21.1 Level: LLT Classification code 10018210 Term: Gestational diabetes mellitus System Organ Class: 100000004868

Interventions

Trade Name: Ursofalk 500mg film-coated tablets Product Name: Ursofalk 500mg film-coated tablets Pharmaceutical Form: Film-coated tablet Trade Name: Metformin 500mg Tablets BP Product Name: Metformin

Eligibility

Sex/Gender

All

Inclusion 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, birth intrapartum and postpartum care at the participating centre (i.e. not planning to move before delivery). Eligibility criteria for GUARD MEC is included in the protocol in section 19. Are the trial subjects under 18? yes Number of subjects for this age range: 158 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 158 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

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 of current pregnancy of >48 mmol/mol or =6.5% (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 (as per Section 5.7 of the protocol). Eligibility criteria for GUARD MEC is included in the protocol in section 19.

Design outcomes

Primary

Measure	Time frame
Main Objective: We would like to assess how well ursodeoxycholic acid works at controlling glucose levels in overweight or obese women with gestational diabetes mellitus, compared to metformin, which is the most commonly used treatment.;Secondary Objective: - We would like to see how each treatment changes the lipid metabolism of both mothers and babies. - We would like to find out if the new treatment is well accepted by women. - We will conduct continuous glucose monitoring. We would like to assess if the information produced by this device offers a more informative assessment to the single glucose test. - We would like to measure the impact on blood vessels and blood pressure as this may affect the health of women with GDM. - We would like to compare adverse outcomes in the pregnancy and fetus. We are also conducting a mechanistic sub-study which intends to look at the gut microbiome of different groups, to assess how these medicines affect the hormonal system, glucose and lipid composition. ;Primary end point(s): Maternal fasting glucose concentration at 36 weeks' gestation measured with a blood sample;Timepoint(s) of evaluation of this end point: Week 36 of gestation	—

Measure

Time frame

Main Objective: We would like to assess how well ursodeoxycholic acid works at controlling glucose levels in overweight or obese women with gestational diabetes mellitus, compared to metformin, which is the most commonly used treatment.;Secondary Objective: - We would like to see how each treatment changes the lipid metabolism of both mothers and babies. - We would like to find out if the new treatment is well accepted by women. - We will conduct continuous glucose monitoring. We would like to assess if the information produced by this device offers a more informative assessment to the single glucose test. - We would like to measure the impact on blood vessels and blood pressure as this may affect the health of women with GDM. - We would like to compare adverse outcomes in the pregnancy and fetus. We are also conducting a mechanistic sub-study which intends to look at the gut microbiome of different groups, to assess how these medicines affect the hormonal system, glucose and lipid composition. ;Primary end point(s): Maternal fasting glucose concentration at 36 weeks' gestation measured with a blood sample;Timepoint(s) of evaluation of this end point: Week 36 of gestation

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Secondary

Measure	Time frame
Secondary end point(s): - Quality of Life assessment (EQ-5D-5L) at baseline and Follow up 2, and treatment satisfaction scores at Follow up 2. - Biomedical and clinical maternal outcomes: 1. Glucose metabolism at baseline, follow up 1 and 2 assessed by: a) Continuous glucose monitoring (CGM) to assess glycaemic control. This will determine the percentage time spent within target (glucose levels 3.9-7.8mmol/L), percentage time spent above target (>7.8mmol/l and =6.7mmol/l), time spent below target (=3.5 and =3.0 mmol/l), measures of glucose variability including glucose standard variation (SD), co-efficient of variation (CV), frequency and duration of glycaemic excursions measured by the area under the curve (AUC) for the pre-specified glucose thresholds. b) Serum concentrations of 1,5-anhydroglucitol; a novel marker of short-term glycaemia 4,43 c) HbA1c concentration; a conventional marker of medium-term glycaemia 2. Lipid metabolism at Follow up 2 assessed by blood triglyceride, total cholesterol, calculated LDL-cholesterol, HDL-cholesterol and free fatty acid concentrations 3. Biochemical analysis of maternal blood for liver function tests at Follow up 2 (ALT, bilirubin, ALP), bile acids, C reactive protein (including highly sensitive analyses) 4. Proportion of women requiring insulin treatment (time until treatment and total dose of insulin required) 5. Maternal gestational weight change at 36 weeks compared to weight at first trimester screening visit. 6. Measurement of vascular responses at Follow up 1 and 2, including: i) maternal pulse wave velocity (PWV), with systolic and diastolic blood pressure, ii) central arterial pressure (cP), and iii) augmentation index (AIx) 7. Estimated blood loss at time of delivery. - Biomedical and clinical neonatal outcomes at birth: 1. Mode of birth (rates of caesarean section (CS),(elective & emergency), assisted vaginal birth and spontaneous vaginal delivery (SVD) 2. Gestational age at birth 3. Apgar scores	—

Measure

Time frame

Secondary end point(s): - Quality of Life assessment (EQ-5D-5L) at baseline and Follow up 2, and treatment satisfaction scores at Follow up 2. - Biomedical and clinical maternal outcomes: 1. Glucose metabolism at baseline, follow up 1 and 2 assessed by: a) Continuous glucose monitoring (CGM) to assess glycaemic control. This will determine the percentage time spent within target (glucose levels 3.9-7.8mmol/L), percentage time spent above target (>7.8mmol/l and =6.7mmol/l), time spent below target (=3.5 and =3.0 mmol/l), measures of glucose variability including glucose standard variation (SD), co-efficient of variation (CV), frequency and duration of glycaemic excursions measured by the area under the curve (AUC) for the pre-specified glucose thresholds. b) Serum concentrations of 1,5-anhydroglucitol; a novel marker of short-term glycaemia 4,43 c) HbA1c concentration; a conventional marker of medium-term glycaemia 2. Lipid metabolism at Follow up 2 assessed by blood triglyceride, total cholesterol, calculated LDL-cholesterol, HDL-cholesterol and free fatty acid concentrations 3. Biochemical analysis of maternal blood for liver function tests at Follow up 2 (ALT, bilirubin, ALP), bile acids, C reactive protein (including highly sensitive analyses) 4. Proportion of women requiring insulin treatment (time until treatment and total dose of insulin required) 5. Maternal gestational weight change at 36 weeks compared to weight at first trimester screening visit. 6. Measurement of vascular responses at Follow up 1 and 2, including: i) maternal pulse wave velocity (PWV), with systolic and diastolic blood pressure, ii) central arterial pressure (cP), and iii) augmentation index (AIx) 7. Estimated blood loss at time of delivery. - Biomedical and clinical neonatal outcomes at birth: 1. Mode of birth (rates of caesarean section (CS),(elective & emergency), assisted vaginal birth and spontaneous vaginal delivery (SVD) 2. Gestational age at birth 3. Apgar scores

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Countries

United Kingdom

Contacts

Public ContactProfessor Catherine Williamson

King’s College London

catherine.williamson@kcl.ac.uk020 7848 6350 / 020 7848 6014

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026