Gestational Treatment With Ursodeoxycholic Acid Compared to Placebo to Reduce Severity of Gestational Diabetes Mellitus Diagnosed at 24-28 Weeks' Gestation (GUARDS)

Gestational Treatment With Ursodeoxycholic Acid Compared to Placebo to Reduce Severity of Gestational Diabetes Mellitus

The trial will compare the influence of treatment with ursodeoxycholic acid (UDCA) compared to placebo on glycaemic control (primary outcome) in women with GDM after a positive diagnosis at 24-28 weeks of gestation.

The investigators will evaluate maternal and fetal lipid and glucose metabolism. Neonatal health outcomes will also be studied, including the rate of LGA. UDCA is used to treat the commonest liver disease of pregnancy, intrahepatic cholestasis of pregnancy (ICP), and has good safety data to support its use in pregnancy 52-57 ., it means, no studies reported any increase in adverse outcomes associated with UDCA treatment. It is noteworthy that in the largest study 52, 8 serious adverse events were reported, 6 of which were in the placebo group, and none were considered to be related to the trial intervention. There were 72 adverse events: 31 in the ursodeoxycholic acid group and 41 in the placebo group. The same number of patients in each group (n=10) reported adverse events related to gastrointestinal disorders.

Study Overview

• Status: Completed
• Conditions: Gestational Diabetes
• Intervention / Treatment: Drug: 500 mg of ursodeoxycholic acid (UDCA); Other: 500 mg of Placebo

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Murcia, Spain, 30120
    • Hospital Clínico Universitario Virgen de la Arrixaca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with GDM diagnosed at 24-28 weeks' gestation in accordance with Spanish guidelines in accordance with NDDG criteria, i.e. two or more glucose concentrations (fasting: ≥ 5.8 mmol/L (105 mg/dL), 1 h: ≥10.6 mmol/L, (190 mg/dL) 2 h: ≥9.2 mmol/L (165 mg/dL), 3 h: ≥ 8.1 mmol/L (145 mg/dL)) after a standard 100g OGTT, two fasting blood glucose levels ≥ 126 mg/dl, on different days, or at random ≥ 200 mg/dL or a plasma glucose value greater than 200 mg/dL after OSullivan test
• Planned antenatal care at the same centre (i.e. not planning to move before delivery).
• Singleton pregnancy.
• Informed and written consent.

Exclusion Criteria:

• Age <18 years;
• Multiple pregnancy in current pregnancy;
• Unconscious or very ill;
• Serious mental illness;
• Learning difficulties;
• Not fluent in local language and absence of interpreter.
• Severe congenital anomaly on ultrasound
• Previous diagnosis of diabetes outside of pregnancy
• 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 (<1 year)
• Significant co-morbidity in the current pregnancy, nephropathy (estimated GF<60ml/min), other physical or psychological conditions likely to interfere with the conduct of the study and/or interpretation of the trial results
• Participating in another intervention study that will influence the outcome of this trial (to be advised by CI or PI).
• Known allergy/hypersensitivity/intolerance to the active substance or excipients.
• Hypersensitivity to Ursodexosolic acid or to the following excipients: Magnesium stearate, cellulose powder, colloidal silica and sodium carboxymethyl starch, gelatin, titanium dioxide, quinoline yellow, orange yellow S, indigotine.
• Patients with a non-functioning gallbladder, in patients with calcified cholesterol stones, radio-opaque stones, radiolucent gallbladder stones.
• Gastric or duodenal ulcer.
• Liver or intestinal disorders that interfere with the enterohepatic circulation: acute cholecystitis that does not subside, cholangitis, biliary obstruction, pancreatitis due to stones, patients with gastrointestinal-biliary fistula.
• Breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ursodeoxycholic Acid; 500 mg of ursodeoxycholic acid (UDCA)	Drug: 500 mg of ursodeoxycholic acid (UDCA); Administration of 500 mg of ursodeoxycholic acid (UDCA) /day
Placebo Comparator: Control; 500 mg of Placebo	Other: 500 mg of Placebo; Administration of 500 mg of placebo /day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal fasting glucose concentration at 36 weeks	aiming to maintain all capillary glucose levels between 3.9-7.8mmol/l (70 - 140 mg/dL). The specific pre- and post-meal self-monitored blood glucose (SMBG) targets are ≤5.3mmol/L before breakfast (95 mg/dL), ≤7.8mmol/L 1-hr post meal (140 mg/dL) and ≤6.7mmol/L (120 mg/dL) 2-hr post meal.	Up to 36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of women requiring insulin treatment	Number of women with insuline treatment	Up to 36 weeks
Proportion of delivery type	Mode of delivery (rates of primary & repeat CS, elective & emergency	Up to 40 weeks
Gestational age at delivery, frequency of preterm delivery	Age of patient	Up to 40 weeks
Infant birth weight	Weight in kg	Up to 40 weeks

Collaborators and Investigators

• Sponsor: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2021
• Primary Completion (Actual): February 9, 2022
• Study Completion (Actual): May 10, 2022

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Diabetes, Gestational; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: IMIB-GU-2019-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No