Obesity - Clinical trial details 

Efficacy of Metformin in Pregnant Obese Women: a Randomised controlled trial

Recruitment status:
Not recruiting
Primary Sponsor:
University of Edinburgh and NHS Lothian (UK)
Recruitment countries:
United Kingdom
Health condition studied:
Obesity, pregnancy
URL:
Link to the clinical trial website

About the trial

Interventions:
Active arm:
Oral metformin tablets given three times daily to a maximum of 500 - 2500 mg daily. Total duration of treatment is from 12 weeks of gestation until delivery (maximum 30 weeks). Total duration of follow up in this study: one year after starting therapy.

Placebo arm:
Oral placebo tablets given three times daily. Total duration of treatment is from 12 weeks of gestation until delivery (maximum 30 weeks). Total duration of follow up in this study: one year after starting therapy.
Key inclusion and exclusion criteria:
  • Inclusion criteria: 1. Caucasian obese (body mass index [BMI] greater than or equal to 30 kg/m^2) pregnant women between 12-0 and 16+0 weeks gestation
    2. Women aged greater than 16 years
    3. Signed informed consent form
  • Exclusion criteria: 1. Non Caucasian women
    2. Women with a BMI less than or equal to 29 kg/m^2
    3. Gestation greater than than 16 weeks
    4. Women with pre-existing diabetes
    5. Women with gestational diabetes in a previous pregnancy
    6. Women with systemic disease requiring regular medication
    7. Gestational diabetes in index pregnancy (diagnosed with 75 g oral glucose tolerance test [OGTT] prior to randomisation)
    8. Previous delivery of a baby less than 3rd centile or previous pregnancy with pre-eclampsia prompting delivery before 32 weeks gestation
    9. A known hypersensitivity to metformin hydrochloride or to any of the excipients
    10. Known abnormalities of the liver (tested prior to randomisation)
    11. Renal failure or renal dysfunction
    12. Acute conditions with the potential to alter renal function such as:
    12.1. Dehydration sufficient to require intravenous infusion
    12.2. Severe infection
    12.3. Shock
    12.4. Intravascular administration of iodinated contrast agents
    12.5. Acute or chronic diseases which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction, shock or hepatic insufficiency, acute alcohol intoxication or alcoholism
    13. Lactation
    14. Multiple pregnancy
  • Age minimum: 
  • Age maximum: 
  • Gender: 
Primary outcomes:
1. Gestational age and sex adjusted birthweight centiles of the baby, measured at delivery of the baby
2. Correlation between maternal insulin resistance (IR) at 36 weeks gestation
3. Adverse pregnancy outcomes, measured cumulatively as pregnancy progresses until after delivery
Secondary outcomes:
1. More detailed measurements of neonatal body composition at birth including ponderal index, skinfold thickness and neonatal fat mass measured using air displacement plethysmography, measured within two weeks of birth
2. Biological mechanisms of metformin action including:
2.1. Change in whole body IR (longitudinal studies at 28 and 36 weeks) and hepatic and skeletal insulin sensitivity (36 weeks)
2.2. Maternal and neonatal inflammatory and lipid and fatty acid indices including C-reactive protein (CRP), interleukin-6 (IL-6), leptin, full lipid profile, non-esterified fatty acids, polyunsaturated fatty acids and plasminogen activator inhibitor 1 (PAI1)/plasminogen activator inhibitor 2 (PAI2) ratio, measured at 36 weeks of pregnancy
2.3. Placental glucocorticoid receptor expression, measured in the placenta after delivery of the baby
2.4. Maternal brachial arterial endothelial dependent flow mediated dilatation (FMD), measured at 36 weeks of pregnancy
2.5. In vitro measurements of maternal myometrial contractility, measured after delivery
3. Changes in maternal anthropometry from the beginning to the end of pregnancy
4. Adverse pregnancy outcomes as a composite measured cumulatively until the end of pregnancy; incidence of low birthweight centile measured at delivery
5. Gas chromatography mass spectrometry measurements of metformin in maternal plasma to determine compliance in samples obtained at 36 weeks of gestation
Target sample size:
400
Study type:
Interventional
Study design:
Multicentre randomised placebo controlled clinical trial
Contacts:
  • Name: Jane Norman
  • Address:  University of Edinburgh Centre for Reproductive Biology The Queens Medical Research Institute 47 Little France Crescent
  • Phone:  +44 (0)131 242 2694
  • Email:  jane.norman@ed.ac.uk
  • Affiliation: 

Technical details

Scientific title:
A multicentre randomised placebo controlled clinical trial of metformin versus placebo in pregnant women to reduce the risk of obesity and metabolic syndrome in their babies
Sources of monetary support:
Medical Research Council (MRC)/National Institutes of Health Research (NIHR) (UK) - Efficacy and Mechanism Evaluation (EME) Programme (ref: EME 08/246/09)
Secondary sponsors:
N/A
Main ID:
ISRCTN51279843
Secondary ID:

EME 08/246/09
Register:
ISRCTN
Date of registration:
14/06/2010
Date of first enrollment:
Feb 1 2011
Last refreshed:
7 October 2014

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