NCT01273584

Brief Summary

Obesity is on the rise in all developed countries. Of particular concern is that more young people including children are being recognised as being overweight or obese. We know from a recent large national enquiry into all maternal and child deaths in the UK, known as CEMACH, that obesity is a major risk both for the mother and her child. When all deaths in women during pregnancy are analysed, obesity comes out as the most common risk factor. Babies of obese mothers are more than 3 times as likely to need admission to the Neonatal Intensive Care Unit. Traditionally, obesity is treated by lifestyle measures encouraging healthy eating and increasing physical activity. Unfortunately these measures are often insufficient to produce significant improvements in weight. If obese women gain little or even no weight during pregnancy, the outcome of the pregnancy is known to be improved. This was shown in a very large study of more than 120, 000 obese women. The drug metformin has been used for years in the treatment of diabetes and more recently for polycystic ovary syndrome (PCOS). Studies in pregnant PCOS women and women with diabetes in pregnancy have shown it to be safe and effective. Fortunately it is relatively cheap and taken as a tablet with meals. Metformin has the great advantage of not causing weight gain and often leads to a small amount of weight loss. It works by improving the body's sensitivity to insulin which is important as resistance to insulin is common in obesity. We have a lot of experience using metformin to treat women with diabetes in pregnancy where it is greatly beneficial. We now wish to examine its potential for obese women who do not have diabetes. We are hoping to show that it will benefit these women by causing less weight gain, less high blood pressure, and less diabetes. We anticipate babies will also have better birth weights, will be easier to deliver naturally, will not need to go to special care baby units and will be healthier.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
450

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2010

Longer than P75 for phase_2

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2010

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

January 7, 2011

Completed
3 days until next milestone

First Posted

Study publicly available on registry

January 10, 2011

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2015

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2015

Completed
Last Updated

January 22, 2016

Status Verified

January 1, 2016

Enrollment Period

4.8 years

First QC Date

January 7, 2011

Last Update Submit

January 21, 2016

Conditions

Pregnancy ComplicationsObesity

Keywords

Metformin, obese, pregnancy, gestational diabetes

Outcome Measures

Primary Outcomes (1)

  • Birth Weight centile (z-score)

    At Birth

Secondary Outcomes (16)

  • Maternal Weight gain

    Weight at recruitment and at end of pregnancy

  • Development of Gestational Diabetes

    28 weeks of pregnancy

  • Development of hypertension/Preeclampsia

    Throughout pregnancy

  • Caesarian Section

    delivery

  • Postpartum haemorrhage

    Delivery

  • +11 more secondary outcomes

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Tablet Metformin 500 mg, starting dose of 1 tablet twice a day with meals, gradually titrated upwards by 1 tablet every week to a maximum dose of 2 tablets three times a day. Tablets started at recruitment and continued till the delivery of the baby

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Tablet Placebo 500 mg, starting dose of 1 tablet twice a day with meals, gradually titrated upwards by 1 tablet every week to a maximum dose of 2 tablets three times a day. Tablets started at recruitment and continued till the delivery of the baby

Drug: Placebo

Interventions

MetforminDRUG

Maximum dosage 500 mg 2 tablets 3 times a day (with each meal) start with 1 tablet twice a day and gradually titrate upwards to maximum dose

Also known as: Glucophage
Metformin
PlaceboDRUG

Placebo maximum dosage 2 tablets 3 times a day ( with meals) start with 1 tablet twice a day and gradually titrate upwards to maximum dose

Also known as: Dummy tablet
Placebo

Eligibility Criteria

Age19 Years - 50 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Obese pregnant women with BMI\>35
  • Informed written consent

You may not qualify if:

  • Diabetes at booking
  • Presence of contra-indication to metformin(renal, liver, heart failure)
  • moving out of study area for pregnancy management
  • Participants who suffer with hyperemesis
  • Participants who are 18 years and below
  • Participants with significantly raised creatinine
  • Participants with high alcohol intake

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Medway Hospital NHS Trust

Gillingham, Kent, ME7 5NY, United Kingdom

Location

Epsom and St Helier University Hospitals NHS Trust

Carshalton, Surrey, SM5 1AA, United Kingdom

Location

Kings College, London

London, SE5 8RX, United Kingdom

Location

Related Publications (6)

  • Balani J, Hyer SL, Rodin DA, Shehata H. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med. 2009 Aug;26(8):798-802. doi: 10.1111/j.1464-5491.2009.02780.x.

    PMID: 19709150BACKGROUND

  • Glueck CJ, Goldenberg N, Wang P, Loftspring M, Sherman A. Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy. Hum Reprod. 2004 Mar;19(3):510-21. doi: 10.1093/humrep/deh109. Epub 2004 Jan 29.

    PMID: 14998944BACKGROUND

  • 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.

    PMID: 18463376BACKGROUND

  • Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. doi: 10.1126/science.1141634. Epub 2007 Apr 12.

    PMID: 17434869BACKGROUND

  • Galtier-Dereure F, Boegner C, Bringer J. Obesity and pregnancy: complications and cost. Am J Clin Nutr. 2000 May;71(5 Suppl):1242S-8S. doi: 10.1093/ajcn/71.5.1242s.

    PMID: 10799397BACKGROUND

  • Syngelaki A, Nicolaides KH, Balani J, Hyer S, Akolekar R, Kotecha R, Pastides A, Shehata H. Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus. N Engl J Med. 2016 Feb 4;374(5):434-43. doi: 10.1056/NEJMoa1509819.

    PMID: 26840133DERIVED

MeSH Terms

Conditions

Pregnancy ComplicationsObesityDiabetes, Gestational

Interventions

Metformin

Condition Hierarchy (Ancestors)

Female Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesOverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsDiabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Study Officials

  • Mr Hassan Shehata, MD MRCOG

    Epsom and St Helier University Hospitals NHS Trust

    PRINCIPAL INVESTIGATOR

  • Dr Steve Hyer, MD, FRCP

    Epsom and St Helier University Hospitals NHS Trust

    STUDY DIRECTOR

  • Prof Kypros Nicolaides, PhD, MRCOG

    King's College London

    PRINCIPAL INVESTIGATOR

  • Dr Jyoti Balani, MD

    Epsom and St Helier University Hospitals NHS Trust

    PRINCIPAL INVESTIGATOR

  • Dr Ranjit Akolekar

    Medway Hospital NHS Trust

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 7, 2011

First Posted

January 10, 2011

Study Start

October 1, 2010

Primary Completion

July 1, 2015

Study Completion

September 1, 2015

Last Updated

January 22, 2016

Record last verified: 2016-01

Data Sharing

IPD Sharing
Will not share

Locations

GB(3)