Clinical trial NCT02394158: Preventing Recurrent Gestational Diabetes With Metformin
Official title: Preventing Recurrent Gestational Diabetes Mellitus With Early Metformin Intervention
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Gestational Diabetes Mellitus
Keywords: Recurrent Gestational Diabetes Mellitus
Prevention
Metformin
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Imperial College Healthcare NHS Trust
name: London North West Healthcare NHS Trust
name: The Novo Nordisk UK Research Foundation
First posted: 2015-03-20
Enrollment: 112
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Development of Gestational Diabetes at any point during the course of pregnancy
timeFrame: From 12 weeks pregnancy until the onset of labour
Secondary outcomes:
measure: Maternal gestational weight gain
timeFrame: Difference between weight at 12 weeks gestation and 36 weeks gestation
measure: Requirement for insulin therapy
timeFrame: From 12 weeks gestation until 36 weeks gestation
measure: Postpartum glucose levels
timeFrame: 6 weeks postpartum
measure: Levels of maternal physical and psychological health as assessed by questionnaires
timeFrame: From 12 weeks gestation until 6 weeks postpartum
measure: Fetal birthweight and birthweight centile
timeFrame: At Birth
measure: Composite of neonatal outcomes (neonatal hypoglycaemia requiring treatment, respiratory distress syndrome requiring oxygen therapy/ continuous positive airway pressure, neonatal hyperbilirubinaemia requiring phototherapy).
timeFrame: At Birth
measure: Cost effectiveness of the intervention
timeFrame: From 12 weeks gestation until 6 weeks postpartum
Other outcomes:
measure: Insulin resistance
timeFrame: From 12 weeks gestation until 6 weeks postpartum
measure: Maternal triglyceride concentrations
timeFrame: From 12 weeks gestation until 6 weeks postpartum
measure: Fetal hyperinsulinaemia
timeFrame: Delivery
Locations:
city: London
country: United Kingdom
facility: Imperial College NHS Trust
city: London
country: United Kingdom
facility: London North West Healthcare Trust
Study officials:
affiliation: Imperial College NHS Trust
name: Stephen Robinson, FRCP, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943.
citation: Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008 May 8;358(19):2003-15. doi: 10.1056/NEJMoa0707193.
citation: Getahun D, Fassett MJ, Jacobsen SJ. Gestational diabetes: risk of recurrence in subsequent pregnancies. Am J Obstet Gynecol. 2010 Nov;203(5):467.e1-6. doi: 10.1016/j.ajog.2010.05.032. Epub 2010 Jul 13.
citation: Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T, Tomlinson JW, Kunz R, Mol BW, Coomarasamy A, Khan KS. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ. 2012 May 16;344:e2088. doi: 10.1136/bmj.e2088.
citation: De Leo V, Musacchio MC, Piomboni P, Di Sabatino A, Morgante G. The administration of metformin during pregnancy reduces polycystic ovary syndrome related gestational complications. Eur J Obstet Gynecol Reprod Biol. 2011 Jul;157(1):63-6. doi: 10.1016/j.ejogrb.2011.03.024. Epub 2011 May 6.