A Feasibility Study Looking at the Use of Glibenclamide and metfoRmin Versus stAndard Care in gEstational diabeteS (GRACES)

The aim of this open label feasibility study is to determine recruitment rates to a randomised trial of glibenclamide compared with insulin (both in addition to maximum tolerated metformin) for the treatment of Gestational Diabetes Mellitus (GDM). This feasibility trial will inform the design of a future substantive multicentre trial to test the hypothesis that combination therapy with glibenclamide and metformin could reduce the number of pregnant women with GDM who require insulin and would be superior to metformin and insulin in terms of acceptability and cost effectiveness.

Women with GDM who have "failed" monotherapy with metformin will be recruited and randomised to either receive glibenclamide (test arm) or standard care with insulin, both in addition to their maximum tolerated dose of metformin. Patients will be recruited from three of the antenatal clinics.

This is a feasibility study in preparation for a large multicentre randomised trial to test the hypothesis that the addition of glibenclamide to metformin (combination therapy) could reduce the number of pregnant women with gestational diabetes mellitus requiring insulin, without compromising glycaemic control or other clinical outcomes. The investigators hypothesise that combination therapy with metformin and glibenclamide is likely to be preferable to metformin and insulin in terms of acceptability and cost.

Study Overview

• Status: Completed
• Conditions: Pregnancy; Gestational Diabetes
• Intervention / Treatment: Drug: Insulin; Drug: Glibenclamide

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom
    • Queen Elizabeth Hospital
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G31 2ER
      • Princess Royal Infirmary
  • Lothian
    • Edinburgh, Lothian, United Kingdom, EH4 2XU
      • Western General Hospital
    • Edinburgh, Lothian, United Kingdom, EH16 4SA
      • Simpson Centre for Reproductive Health, Royal Infirmary Hospital, Edinburgh
  • West Lothian
    • Livingston, West Lothian, United Kingdom
      • St Johns Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women diagnosed with gestational diabetes who fail to achieve "adequate glycaemic control" on maximum tolerated dose metformin
• Inadequate glycaemic control is defined according to the SIGN 116 guidelines.

Exclusion Criteria:

• Pregnant women requiring insulin prior to 20 weeks gestation or after 36 weeks gestation.
• Pregnant women not taking at least 500mg metformin daily.
• Patients with suspected Type 1 diabetes mellitus presenting in pregnancy.
• Women with allergies to either glibenclamide or insulin or any of their excipients.
• Women with any contraindications to sulfonylurea therapy.
• Women unable to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Current Standard Care; Insulin + Metformin	Drug: Insulin
Active Comparator: Treatment; Glibenclamide + Metformin	Drug: Glibenclamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of women willing to be randomised	Retention - proportion of women randomised who remain in the study to provide outcomes; Adherence - proportion of clinicians who adhere to the treatment regimen(s)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycaemic control	Safety - number of hypoglycaemic episodes needing treatment, any other adverse events	2 weekly
Patient satisfaction	assessed by visual analogue scale	36-38 weeks gestation
Clinical outcomes	Change in maternal weight between booking and 36 weeks	36 weeks
Clinical outcome	Mode and gestation of delivery.	40 weeks
Clinical Outcome	Birthweight centile (adjusted for sex and gestation at birth)	40 weeks
Clinical Outcome	Incidence of neonatal hypoglycaemia (defined as any of the following: blood glucose <2.6 mmol/l) in first 48hrs age, or given intravenous glucose or any other drug to increase blood glucose)	2 days

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: Chief Scientist Office of the Scottish Government
• Investigators: Principal Investigator: Jane E Norman, MD, University of Edinburgh

Publications and helpful links

General Publications

• Reynolds RM, Denison FC, Juszczak E, Bell JL, Penneycard J, Strachan MWJ, Lindsay RS, Alexander CI, Love CDB, Whyte S, Mackenzie F, Stenson B, Norman JE. Glibenclamide and metfoRmin versus stAndard care in gEstational diabeteS (GRACES): a feasibility open label randomised trial. BMC Pregnancy Childbirth. 2017 Sep 22;17(1):316. doi: 10.1186/s12884-017-1505-3.

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: February 11, 2014
• First Submitted That Met QC Criteria: March 4, 2014
• First Posted (Estimate): March 6, 2014

Study Record Updates

• Last Update Posted (Estimate): December 8, 2016
• Last Update Submitted That Met QC Criteria: December 7, 2016
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Pregnancy; Metformin; Glycaemic control; Gestational diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Diabetes Mellitus; Diabetes, Gestational; Hypoglycemic Agents; Physiological Effects of Drugs; Glyburide
• Other Study ID Numbers: GRACES; 2013-004706-25 (EudraCT Number)