Ursodeoxycholic Acid vs Metformin in Gestational Diabetes Mellitus

NCT04407650 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: 264693
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gestational Diabetes

Outcome Measures

Primary Outcomes (1)

• Glycaemic control

  Maternal fasting glucose concentration in blood sample

  Gestational week 36

Secondary Outcomes (25)

• Acceptability

  Gestational week 36

• Biomedical outcomes: continuous glucose monitoring

  Baseline (week 28), Follow up 1 (week 32), Follow up 2 (week 36)

• Biomedical outcomes: 1,5-anhydroglucitol

  Baseline (week 28), Follow up 1 (week 32), Follow up 2 (week 36)

• Biomedical outcomes: glucose control by HbA1c

  Baseline (week 28), Follow up 2 (week 36)

• Biomedical outcomes: lipids

  Follow up 2 (week 36)

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Oral 1000 mg BD

Drug: Metformin

Ursodeoxycholic acid

EXPERIMENTAL

Oral 500 mg BD

Drug: Ursodeoxycholic Acid

Interventions

Metformin DRUG

Patients will be randomized to each intervention using minimisation: * BMI category (Overweight/Obese), * Previous history of GDM, * Disease severity (baseline fasting glucose ≤6.2 or \>6.2), * Recruitment centre

Metformin

Ursodeoxycholic Acid DRUG

Patients will be randomized to each intervention using minimisation: * BMI category (Overweight/Obese), * Previous history of GDM, * Disease severity (baseline fasting glucose ≤6.2 or \>6.2), * Recruitment centre

Ursodeoxycholic acid

Eligibility Criteria

• Age: 16 Years - 45 Years
• Gender Eligibility Details: Only pregnant people allowed study entry, irrespective of gender indentity
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).
• Overweight or obese (Booking BMI ≥25 kg/m2)
• Planned antenatal, intrapartum and postpartum care at the participating centre (i.e. not planning to move before delivery).

You may not qualify if:

• Unwilling/unable to give written informed consent and comply with the requirements of the study protocol
• Multiple pregnancies (twins, triplets etc) in current pregnancy
• Congenital anomaly on ultrasound requiring fetal medicine input
• Previous diagnosis of diabetes outside pregnancy
• HbA1c at booking \>48 mmol/mol or ≥6.5% during current pregnancy (if available)
• 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.
• 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.
• Not fluent in English and absence of interpreter or translation services (ie telephone translation services)
• 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.
• Known allergy/hypersensitivity/intolerance to the active substance or excipients, or patients taking any medications which are contraindicated as per IMP SmPC

Sponsors & Collaborators

• King's College London: lead
• Guy's and St Thomas' NHS Foundation Trust: collaborator

Study Sites (1)

Guy's and St Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

Related Publications (1)

• Lovell H, Mitchell A, Ovadia C, Pitrelli N, Briley A, Singh C, Marschall HU, Cruickshank K, Murphy H, Seed P, Williamson C. 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. Trials. 2022 Jul 19;23(1):571. doi: 10.1186/s13063-022-06462-y.

  PMID: 35854327 DERIVED

MeSH Terms

Conditions

Diabetes, Gestational

Interventions

Metformin; Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Caroline Ovadia, CI

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot Phase 4 Randomised Controlled Trial

Study Record Dates

• First Submitted: May 14, 2020
• First Posted: May 29, 2020
• Study Start: July 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: May 31, 2025
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)