PRoDroME: Preventing Recurrent Gestational Diabetes With Metformin

Sponsor

Imperial College London (Other)

Overall Status

Unknown status

CT.gov ID

NCT02394158

Collaborator

Imperial College Healthcare NHS Trust (Other), London North West Healthcare NHS Trust (Other), The Novo Nordisk UK Research Foundation (Other)

112

Enrollment

Locations

Arms

56.1

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study Hypothesis: Intervention with metformin therapy early in pregnancy will prevent gestational diabetes mellitus recurring in previously affected pregnancies.

Condition or Disease	Intervention/Treatment	Phase
Gestational Diabetes Mellitus	Drug: Metformin Drug: placebo	Phase 4

Detailed Description

Gestational diabetes mellitus (GDM) is a common medical complication of pregnancy and is associated with increased risks to mother and baby. The incidence is increasing reflecting changing pre-gravid female demographics. Once one pregnancy is complicated by GDM, subsequent pregnancies are more likely to be affected by the same condition. This reported risk of recurrence is estimated to range between 35 and 80%, with non-caucasian ethnicity being the strongest predictor of GDM recurrence. Evidence regarding further predictors of recurrent GDM is conflicting and measures that might prevent recurrence need exploring.

Metformin is commonly used in the treatment of established GDM and has been shown to reduce the incidence of GDM in the context of polycystic ovarian syndrome.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

112 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Prevention

Official Title:

Preventing Recurrent Gestational Diabetes Mellitus With Early Metformin Intervention

Actual Study Start Date :

Jan 27, 2015

Anticipated Primary Completion Date :

Sep 30, 2019

Anticipated Study Completion Date :

Sep 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intervention arm Metformin Metformin (500mg tablets) to start at a dose of 500mg once daily with an increase of 500mg every five days until the maximum dose of 1000mg twice daily is reached.	Drug: Metformin
Placebo Comparator: Control arm placebo Matched placebo tablets (500mg) to start at a dose of 500mg once daily with an increase of 500mg every five days until the maximum dose of 1000mg twice daily is reached.	Drug: placebo

Arm

Intervention/Treatment

Active Comparator: Intervention arm Metformin

Metformin (500mg tablets) to start at a dose of 500mg once daily with an increase of 500mg every five days until the maximum dose of 1000mg twice daily is reached.

Drug: Metformin

Placebo Comparator: Control arm placebo

Matched placebo tablets (500mg) to start at a dose of 500mg once daily with an increase of 500mg every five days until the maximum dose of 1000mg twice daily is reached.

Drug: placebo

Outcome Measures

Primary Outcome Measures

Development of Gestational Diabetes at any point during the course of pregnancy [From 12 weeks pregnancy until the onset of labour]

Secondary Outcome Measures

Maternal gestational weight gain [Difference between weight at 12 weeks gestation and 36 weeks gestation]
Requirement for insulin therapy [From 12 weeks gestation until 36 weeks gestation]
Postpartum glucose levels [6 weeks postpartum]
Levels of maternal physical and psychological health as assessed by questionnaires [From 12 weeks gestation until 6 weeks postpartum]
Fetal birthweight and birthweight centile [At Birth]
Composite of neonatal outcomes (neonatal hypoglycaemia requiring treatment, respiratory distress syndrome requiring oxygen therapy/ continuous positive airway pressure, neonatal hyperbilirubinaemia requiring phototherapy). [At Birth]
Cost effectiveness of the intervention [From 12 weeks gestation until 6 weeks postpartum]
Difference in requirement for medical services and unplanned hospital/ General Practitioner attendances between the two arms

Other Outcome Measures

Insulin resistance [From 12 weeks gestation until 6 weeks postpartum]
Maternal triglyceride concentrations [From 12 weeks gestation until 6 weeks postpartum]
Fetal hyperinsulinaemia [Delivery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Singleton pregnancy;
8-22 weeks gestation
Previous pregnancy complicated by gestational diabetes

Exclusion Criteria:

Established pre-existing diabetes (including unrecognised diabetes defined as a fasting plasma glucose ≥ 7.0mmol/L and/ or HbA1c ≥ 48mmol/mol); Contraindications to metformin therapy (creatinine ≥ 130μmol/L/ alanine transaminase ≥ 2.0 x upper limit normal/ previous intolerance to metformin)
Planned continued antenatal care/ delivery at centre not included in trial
Planned fast for cultural/ religious reasons e.g. Ramadan