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Pregnancy ComplicationsPhase 2/3MOPNCT01273584

Metformin in Obese Non-diabetic Pregnant Women

A Phase 2/3 study testing Metformin in people with Pregnancy Complications and Obesity, run by Epsom and St Helier University Hospitals NHS Trust at 3 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 19 to 50 years, women only
Conditions the study is for
Pregnancy Complications, Obesity
What is being tested?
Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
450 participants
Where
3 sitesUnited Kingdom
Study dates
Oct 2010to Sep 2015
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 50 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

3 sites in 1 country.

United Kingdom3 sites
  • Epsom and St Helier University Hospitals NHS Trust

    Carshalton, Surrey, SM5 1AA

  • Medway Hospital NHS Trust

    Gillingham, Kent, ME7 5NY

  • Kings College, London

    London, SE5 8RX

Other trials in United Kingdom

About this study

Official title: Does Metformin Improve Pregnancy Outcomes (Incidence of LGA (≥90% Birth Weight Centile) Babies, Onset of Maternal GDM, Hypertension, PET, Macrosomia, Shoulder Dystocia, Admission to SCBU) in Obese Non-diabetic Women?

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.

Read more

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.

Read the detailed description

Obesity in Pregnancy has been identified by the Confidential Enquiry into Maternal and Child Health [CEMACH] report (2007) as a major health risk to mother and baby:

  • 35% of women who died were obese
  • 30% of the mothers who had a stillbirth or a neonatal death were obese

Obesity increases the risk of miscarriages, GDM, pregnancy-induced hypertension/PET, Caesarean sections, deep venous thrombosis, puerperal sepsis and LGA babies. There is a 5-fold increase in costs of antenatal care. Results from various studies have concluded that limited or no weight gain during pregnancy in obese women results in more favourable pregnancy outcomes. By improving insulin sensitivity and enhancing GLP-1 release, metformin is associated with weight reduction by approximately 5.8% with no serious adverse events.

The aim of this study is to test the hypothesis that management of obese non-diabetic pregnant women with standardised life-style intervention (diet and physical activity) plus metformin will lead to improved maternal and perinatal outcomes compared with life-style intervention alone.

The study will also seek to determine whether metformin will improve body fat distribution as measured by bioimpedance during pregnancy with particular emphasis on metabolic active visceral fat.

Genetic studies will investigate whether patients with polymorphisms of the candidate fat gene, FTO gene, differ in their response to metformin and whether this is associated with favourable pregnancy outcomes.

This is a randomised, multicentre, double blind, placebo-controlled trial.Assuming power 90%, significance level 5% and 2-sided testing, we will recruit 425 subjects per arm of the trial.This will allow the detection of a difference in mean centile (z-score) of 0.21 standard deviations.

All women will undergo oral glucose tolerance testing at booking and at 28 wks; those found to have GDM at 28 weeks will commence home glucose monitoring and will receive metformin if glucose values are outside target range.

The primary outcome will be the birth weight centile (z score). Secondary outcomes include maternal and neonatal outcomes, body composition scores, patient satisfaction and infant development at 2 years. The relation between FTO gene variants and pregnancy outcomes will be examined. Parametric and non-parametric tests will be used as appropriate.

This is a multicentre trial to be undertaken in 7 centres in the UK over a period of 3 years in order to reach the required sample size. Mr Hassan Shehata, Clinical lead and Consultant Obstetrician and Gynecologist is the Chief Investigator of the trial and the trial will be centrally coordinated by Dr Jyoti Balani at Epsom and St Helier University Hospital. In the first phase of the research, we would be recruiting a total of 546 pregnant women into the trial. 200 women would be recruited at Epsom and St Helier Hospital, 200 women at kings college Hospital under the supervision of Professor Kypros Nicolaides and 146 at Royal Surrey County Hospital under the supervision of Dr Lesley Roberts.

Given the low cost of metformin and the potentially high impact on health for both mother and baby, we anticipate the study will show metformin to be highly cost-effective. We anticipate improved patient satisfaction scores in those taking metformin as they gain less weight and develop fewer complications. Improvements in the metabolic milieu during interuterine growth is expected to improve long term outcome for the infants of mothers treated with metformin.

Benefits to patients will be immediate from the time the project's findings are presented. Implementation into clinical practice is expected to greatly benefit the NHS.

Being tested
Metformin, Placebo
Keywords
Metformin, obese, pregnancy, gestational diabetes
Medical subject headings
Pregnancy Complications, Obesity, Diabetes, Gestational

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called Glucophage

    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

  • PlaceboDrug

    Also called Dummy tablet

    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

Study groups in NCT01273584
Study groupRoleWhat they receive
MetforminActive comparatorTablet 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
Receives: Drug: Metformin
PlaceboPlacebo comparatorTablet 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
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Birth Weight centile (z-score)

    Measured: At Birth

Secondary outcomes (16)
  1. Maternal Weight gain

    Measured: Weight at recruitment and at end of pregnancy

  2. Development of Gestational Diabetes

    A Glucose Tolerance Test would be conducted at 28 wks of pregnancy to diagonose diabetes

    Measured: 28 weeks of pregnancy

  3. Development of hypertension/Preeclampsia

    Blood Pressure and urinary proteins would be monitored at each visit to diagonose hypertension/Preeclampsia

    Measured: Throughout pregnancy

  4. Caesarian Section

    Measured: delivery

  5. Postpartum haemorrhage

    Measured: Delivery

  6. Neonatal Hypoglycemia

    Blood glucose is checked within 2 hours after birth and before each feeding until consecutive glucose values of 2.6 mmol per liter (46.8 mg per deciliter) or greater were achieved.

    Neonatal hypoglycemia was defined as 2 capillary plasma glucose levels< 2.6 mmol/l at least 30 minutes apart.

    Measured: within 2 hours after birth and immediate post birth

  7. Prematurity

    Born < 37 weeks gestation

    Measured: Delivery

  8. Hyperbilirubinemia

    Hyperbilirubinemia requiring phototherapy

    Measured: at birth and after

  9. Polycythaemia

    Cord blood hematocrit > 0.6

    Measured: At birth

  10. Respiratory Distress

    4 or more hours of respiratory suppory or oxygen with associated diagnosis

    Measured: At birth and within 24 hours

  11. Macrosomia/Large for Gestational Age

    Birth weight>90th centile based on appropriate growth standards

    Measured: At birth

  12. Birth Trauma

    Shoulder dystocia, brachial plexus injury

    Measured: At birth

  13. Apgar score <6

    Measured: 5 minutes after birth

  14. Admission to level 2 or greater neonatal unit

    If yes, then length of stay

    Measured: at birth and immediately after

  15. Stillbirth/Intrauterine deaths

    Measured: Throughout pregnancy

  16. 2nd trimester miscarriages

    Measured: in 2nd trimester of pregnancy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2011 (estimated)
  2. Study startOct 2010
  3. Primary completionJul 2015
  4. Study completionSep 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
450 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01273584
Sponsor's protocol ID
WCH/2008/001
Other IDs
2008-005892-83, 2008
Acronym
MOP
Status last verified
Jan 2016
First submitted
7 Jan 2011
Last updated
22 Jan 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 19709150
  • 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.

    PubMed 14998944
  • 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.

    PubMed 18463376
  • 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.

    PubMed 17434869
  • 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.

    PubMed 10799397
  • 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.

    PubMed 26840133

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Metformin in people with Pregnancy Complications and Obesity, run by Epsom and St Helier University Hospitals NHS Trust at 3 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Birth Weight centile (z-score) (time frame: At Birth). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01273584, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2016.

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