Gestational DiabetesPhase 3POEMNCT02947503
Pregnancy Outcomes: Effects of Metformin Study (POEM Study)
A Phase 3 study testing Metformin TEVA 850 mg in people with Gestational Diabetes and Insulin Resistance, run by Bethesda Diabetes Research Center at 4 sites in Netherlands.
Trial summary
One approach to prevent the rising burden of diabetes is to address the issue of gestational diabetes mellitus (GDM). GDM has a growing prevalence up to 5-10% (and even higher in specific subgroups), with a pregnant population becoming older and more obese worldwide. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Gestational Diabetes, Insulin Resistance
- What is being tested?
- Metformin TEVA 850 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 4 sitesNetherlands
- Study dates
- 26 Nov 2019to Dec 2043
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Pregnant women with GDM defined as a Fasting Plasma Glucose (FPG) > 5,3 mMol and/or an Oral Glucose Tolerance test (OGTT) with a Plasma glucose (PG) > 7,8 mMol, two hours after the oral intake of 75 gram glucose
- Written informed consent
- Age 18-45 years
- Gestational age at inclusion 16-32 weeks
- Glycohemoglobin test (HbA1c) at inclusion ≤ 48 mmol/mol (6.5% Hb)
Who cannot join
- Diabetes mellitus before pregnancy, except previous GDM
- Proteinuria: Urine Albumin-to-Creatinine Ratio (UACR) > 35 mg/mmol at screening
- Malignancy during the last 5 years before inclusion, except non-melanoma skin cancer
- Psychiatric and/or mood disorder potentially affecting compliance of treatment
- Chronic liver disease and/or Alanine aminotransferase aspartate transaminase (ASAT) and/or Alanine aminotransferase (ALAT) > 3x Upper Limit of Normal (ULN).
- Chronic renal failure with a Glomerular filtration rate (GFR) < 45 ml/min/1.73m2
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- Chronic pulmonary failure with hypoxia
- Significantly uncontrolled hypertension - Systolic blood pressure (SBP) > 160 mm Hg despite medical treatment
- Chronic treatment with corticosteroids
- Intolerance for metformin and/or earlier use of metformin in this pregnancy
- Membership of the POEM study group
- Severe foetal anomaly at inclusion - like major neural tube and/or cardiac malformation
- Ruptured membranes
- Multiple pregnancy
- Inability to understand or read the Dutch language
- Bariatric surgery in medical history
- Hyperemesis gravidarum
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Louise Smit contact
Netherlands4 sites, 4 recruiting
- Recruiting
Martini hospital Groningen
Groningen
- Recruiting
University Medical Center Groningen
Groningen
- Recruiting
Treant Zorggroep
Hoogenveen, Emmen, Stadskanaal
- Recruiting
Medical Center Leeuwarden
Leeuwarden
About this study
Official title: Pregnancy Outcomes: Effects of Metformin Study (POEM Study), a Long Term Randomized Controlled Study in Gestational Diabetes
One approach to prevent the rising burden of diabetes is to address the issue of gestational diabetes mellitus (GDM). GDM has a growing prevalence up to 5-10% (and even higher in specific subgroups), with a pregnant population becoming older and more obese worldwide. GDM increases the risks of complications during pregnancy, at delivery and on the longer term, like type 2 diabetes (T2D) and persistent obesity, in mother and child. Moreover, insulin added to diet as the standard care for GDM has disadvantages for mother (maintenance of hyperinsulinaemia, increasing weight and blood pressure) and child (macrosomia, hypoglycaemia) with related adverse pregnancy outcomes. Metformin, as an insulin sensitizer targeting the cause of GDM, may have essential benefits, as suggested by observational studies. However, RCTs with metformin (early positioned in the treatment of GDM) are still lacking. The POEM study is the first Randomized controlled trial (RCT) in GDM to test the hypothesis that metformin, early given from the start of the diagnosis GDM, on top of diet and lifestyle improves clinically relevant pregnancy outcomes in mother and child during pregnancy, at delivery and on the longer term - up to 20 years after birth.
Read the detailed description
The POEM study was designed to investigate the effects of metformin on top of diet and lifestyle (with insulin rescue if needed) in GDM on eight clinically relevant pregnancy outcomes at delivery, summarized by means of an integrated, newly developed score, the GDM Outcome Score (GOS), and on other relevant outcomes on the longer term in mother and child. The investigators hypothesize that metformin given to women with GDM from the start of the diagnosis reduces risks resulting in relevant health benefits for mother and child during pregnancy, at delivery, and many years thereafter.
The POEM study is a randomized controlled intervention study, consisting of three phases:
- Phase A - from inclusion until six weeks after delivery; intervention study with and without exposure of metformin in mother and (unborn) child: two arms after randomization with 1:1 allocation to Diet + Lifestyle + Metformin (DLM) or Diet + Lifestyle (DL);
- Phase B - from six weeks until 1 year after delivery; intervention study with exposure of DLM vs DL in mother;
- Phase C - from 1 until 20 years after delivery; observational extension study of mother and child without study medication.
- Conditions
- Gestational Diabetes, Insulin Resistance
- Being tested
- Metformin TEVA 850 mg
- Keywords
- Gestational Diabetes, Insulin Resistance, Metformin, Hyperinsulinaemia, Prevention of Complications, Long Term Study, Mother and Child, Health Benefits
- Medical subject headings
- Diabetes, Gestational, Insulin Resistance, Hyperinsulinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin TEVA 850 mgDrug
Also called Metformin
At inclusion, patients (N=500) will be randomized 1:1 to metformin vs usual care (850 mg tablets, 3 times daily or, if tolerance is suboptimal, a lower maximally tolerated dose, 1-2 times daily), on top of diet and lifestyle, with an insulin rescue in both arms if needed.
| Study group | Role | What they receive |
|---|---|---|
| Metformin on top of usual care | Active comparator | Metformin TEVA 850 mg (1-3 times daily) added to usual care from start of the diagnosis GDM.
Usual care has been defined as intensive counselling for diet and lifestyle plus insulin therapy if needed.
Intervention: metformin TEVA 850 mg (1-3 times daily) on top of usual care. Receives: Drug: Metformin TEVA 850 mg |
| Usual care | No intervention | Usual care from start of the diagnosis GDM. Control group without metformin. Usual care has been defined as intensive counselling for diet and lifestyle plus insulin therapy if needed. Intervention: usual care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
GDM Outcome Score (GOS) in Phase A
An aggregate score of eight clinically relevant endpoints, as previously defined:
- pregnancy related hypertension, including (pre-) eclampsia, according validated guidelines,
- large for gestational age baby (LGA) at delivery according validated guidelines,
- premature delivery with a gestational age < 37 weeks,
- instrumental delivery,
- caesarean delivery,
- birth trauma, like fractures of clavicle and humerus, subdural / intracerebral haemorrhage,
- neonatal hypoglycaemia, defined as blood glucose < 2.6 mmol/l,
- admission for neonatal intensive care.
Measured: 30 months
T2D and obesity at the end of Phase B
Incidence of maternal T2DM Weight (kg) and BMI (category) development mother Weight (kg) and BMI (percentile) development child
Measured: 42 months
Development of T2D and obesity during Phase C
Incidence of maternal T2DM Weight (kg) and BMI (category) development mother Weight (kg) and BMI (percentile) development child
Measured: 282 months
Secondary outcomes (4)
Secondary Outcome measures phase A mother
Maternal outcome score (MOS)
- Caesarean delivery (yes=1, no=0)
- (Pre-)eclampsia, HELPP and PIH (if at least one is diagnosed=yes=1,no=0)
- Maternal mortality (yes=1, no=0)
- Postpartum haemorrhage (blood loss > 1000 ml)(yes=1, no=0)
- Thrombosis (yes=1, no=0)
For each individual component applies: if occured=1 point. If not occured =0 points. A total score per individual will be calculated (0-5 for MOS). Each component on its own is also a secondary outcome measure.
Measured: 30 months
Secondary Outcome measures phase A child
Neonatal outcome score (NOS)**
- IRDS requiring oxygen therapy (CPAP, optiflow, mechanical ventilation or surfactant) (yes=1, no=0)
- Stillbirth or neonatal death (yes=1, no=0)
- Preterm birth <37 weeks (yes=1, no=0)
- Shoulder dystocia (yes=1, no=0)
- Instrumental delivery (yes=1, no=0)
- Caesarean delivery (yes=1, no=0)
- Neonatal hypoglycaemia < 2.6 mml/l (yes=1, no=0)
- Neonatal jaundice needing phototherapy (yes=1, no=0)
- NICU admission (yes=1, no=0)
- Apgar score < 7 at 5 minutes (yes=1, no=0)
- Congenital anomaly (to a list, if one anomaly = yes = 1, no=0)
For each individual component applies: if occured=1. If not occured=0. A total score per individual will be calculated (0-11 for NOS). Each component on its own is also a secondary outcome measure.
Apgar score as a variable (1-10) at 1, 5, 10 min Foetal weight at delivery in grams
Measured: 30 months
Secondary outcome measures phase B
Hypertension development (yes/no) Thrombotic and CVD events (yes/no) Development of chronic disease (according to list - yes/no)
Gonadal and gender development (to be determined: question(naires) + potentially additional measurements from research blood panel) Puberty and maturation (to be determined: question(naires) + potentially additional measurements from research blood panel) Educational and intellectual development (levels of education completed) Development of chronic disease (according to list - yes/no)
Measured: 42 months
Secondary outcome measures phase C
Hypertension development (yes/no) Thrombotic and CVD events (yes/no) Development of chronic disease (according to list - yes/no)
Gonadal and gender development (to be determined: question(naires) + potentially additional measurements from research blood panel) Puberty and maturation (to be determined: question(naires) + potentially additional measurements from research blood panel) Educational and intellectual development (levels of education completed) Development of chronic disease (according to list - yes/no)
Measured: 282 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2016 (estimated)
- Study start26 Nov 2019
- Primary completionDec 2043 (estimated)
- Study completionDec 2043 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gestational DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bethesda Diabetes Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center, University Medical Center Groningen, Frisius Medisch Centrum, Martini Hospital Groningen, Treant Zorggroep, Nij Smellinghe Hosptial
- Responsible party
- Sponsor
- Investigators
- Adriaan Kooy, Dr., Principal investigator, BDRC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02947503
- Sponsor's protocol ID
- NL 2016 POEMS
- Acronym
- POEM
- Status last verified
- Feb 2022
- First submitted
- 20 Oct 2016
- Last updated
- 10 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be available upon reasonable request. The study protocol will be submitted for publication in a peer reviewed journal.
Publications
van Hoorn EGM, van Dijk PR, Prins JR, Lutgers HL, Hoogenberg K, Erwich JJHM, Kooy A. Pregnancy Outcomes: Effects of Metformin (POEM) study: a protocol for a long-term, multicentre, open-label, randomised controlled trial in gestational diabetes mellitus. BMJ Open. 2022 Mar 30;12(3):e056282. doi: 10.1136/bmjopen-2021-056282.
PubMed 35354633
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pregnancy Outcomes: Effects of Metformin Study (POEM Study), a Long Term Randomized Controlled Study in Gestational Diabetes
- ClinicalTrials.gov ID
- NCT02947503
- Acronym / sponsor ID
- POEM / NL 2016 POEMS
- Conditions
- Gestational Diabetes, Insulin Resistance
- Keywords
- Gestational Diabetes, Insulin Resistance, Metformin, Hyperinsulinaemia, Prevention of Complications, Long Term Study, Mother and Child, Health Benefits
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Bethesda Diabetes Research CenterUniversity, hospital or other
- Collaborators
- Maastricht University Medical Center, University Medical Center Groningen, Frisius Medisch Centrum, Martini Hospital Groningen, Treant Zorggroep, Nij Smellinghe Hosptial
- Study start
- 26 Nov 2019 (actual)
- Primary completion
- Dec 2043 (estimated)
- Study completion
- Dec 2043 (estimated)
- First posted
- 28 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One approach to prevent the rising burden of diabetes is to address the issue of gestational diabetes mellitus (GDM). GDM has a growing prevalence up to 5-10% (and even higher in specific subgroups), with a pregnant population becoming older and more obese worldwide. GDM increases the risks of complications during pregnancy, at delivery and on the longer term, like type 2 diabetes (T2D) and persistent obesity, in mother and child. Moreover, insulin added to diet as the standard care for GDM has disadvantages for mother (maintenance of hyperinsulinaemia, increasing weight and blood pressure) and child (macrosomia, hypoglycaemia) with related adverse pregnancy outcomes. Metformin, as an insulin sensitizer targeting the cause of GDM, may have essential benefits, as suggested by observational studies. However, RCTs with metformin (early positioned in the treatment of GDM) are still lacking. The POEM study is the first Randomized controlled trial (RCT) in GDM to test the hypothesis that metformin, early given from the start of the diagnosis GDM, on top of diet and lifestyle improves clinically relevant pregnancy outcomes in mother and child during pregnancy, at delivery and on the longer term - up to 20 years after birth.
Detailed description
The POEM study was designed to investigate the effects of metformin on top of diet and lifestyle (with insulin rescue if needed) in GDM on eight clinically relevant pregnancy outcomes at delivery, summarized by means of an integrated, newly developed score, the GDM Outcome Score (GOS), and on other relevant outcomes on the longer term in mother and child. The investigators hypothesize that metformin given to women with GDM from the start of the diagnosis reduces risks resulting in relevant health benefits for mother and child during pregnancy, at delivery, and many years thereafter.
The POEM study is a randomized controlled intervention study, consisting of three phases:
- Phase A - from inclusion until six weeks after delivery; intervention study with and without exposure of metformin in mother and (unborn) child: two arms after randomization with 1:1 allocation to Diet + Lifestyle + Metformin (DLM) or Diet + Lifestyle (DL);
- Phase B - from six weeks until 1 year after delivery; intervention study with exposure of DLM vs DL in mother;
- Phase C - from 1 until 20 years after delivery; observational extension study of mother and child without study medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin on top of usual care | Active comparator | Drug: Metformin TEVA 850 mgMetformin TEVA 850 mg (1-3 times daily) added to usual care from start of the diagnosis GDM. Usual care has been defined as intensive counselling for diet and lifestyle plus insulin therapy if needed. Intervention: metformin TEVA 850 mg (1-3 times daily) on top of usual care. |
| Usual care | No intervention | –Usual care from start of the diagnosis GDM. Control group without metformin. Usual care has been defined as intensive counselling for diet and lifestyle plus insulin therapy if needed. Intervention: usual care. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Pregnant women with GDM defined as a Fasting Plasma Glucose (FPG) > 5,3 mMol and/or an Oral Glucose Tolerance test (OGTT) with a Plasma glucose (PG) > 7,8 mMol, two hours after the oral intake of 75 gram glucose
- Written informed consent
- Age 18-45 years
- Gestational age at inclusion 16-32 weeks
- Glycohemoglobin test (HbA1c) at inclusion ≤ 48 mmol/mol (6.5% Hb)
Key exclusion criteria (17 listed)
- Diabetes mellitus before pregnancy, except previous GDM
- Proteinuria: Urine Albumin-to-Creatinine Ratio (UACR) > 35 mg/mmol at screening
- Malignancy during the last 5 years before inclusion, except non-melanoma skin cancer
- Psychiatric and/or mood disorder potentially affecting compliance of treatment
- Chronic liver disease and/or Alanine aminotransferase aspartate transaminase (ASAT) and/or Alanine aminotransferase (ALAT) > 3x Upper Limit of Normal (ULN).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin TEVA 850 mgAlso: MetforminAt inclusion, patients (N=500) will be randomized 1:1 to metformin vs usual care (850 mg tablets, 3 times daily or, if tolerance is suboptimal, a lower maximally tolerated dose, 1-2 times daily), on top of diet and lifestyle, with an insulin rescue in both arms if needed. | Drug | Metformin on top of usual care |
Primary outcome
GDM Outcome Score (GOS) in Phase A
Time frame: 30 months
An aggregate score of eight clinically relevant endpoints, as previously defined: 1. pregnancy related hypertension, including (pre-) eclampsia, according validated guidelines, 2. large for gestational age baby (LGA) at delivery according validated guidelines, 3. premature delivery with a gestational age < 37 weeks, 4. instrumental delivery, 5. caesarean delivery, 6. birth trauma, like fractures of clavicle and humerus, subdural / intracerebral haemorrhage, 7. neonatal hypoglycaemia, defined as blood glucose < 2.6 mmol/l, 8. admission for neonatal intensive care.
T2D and obesity at the end of Phase B
Time frame: 42 months
Incidence of maternal T2DM Weight (kg) and BMI (category) development mother Weight (kg) and BMI (percentile) development child
Development of T2D and obesity during Phase C
Time frame: 282 months
Incidence of maternal T2DM Weight (kg) and BMI (category) development mother Weight (kg) and BMI (percentile) development child
4 secondary outcomes
Secondary Outcome measures phase A mother
Time frame: 30 months
Secondary Outcome measures phase A child
Time frame: 30 months
Secondary outcome measures phase B
Time frame: 42 months
Secondary outcome measures phase C
Time frame: 282 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2022.
- Derived from this study: PubMed 35354633van Hoorn EGM, van Dijk PR, Prins JR, Lutgers HL, Hoogenberg K, Erwich JJHM, Kooy A. Pregnancy Outcomes: Effects of Metformin (POEM) study: a protocol for a long-term, multicentre, open-label, randomised controlled trial in gestational diabetes mellitus. BMJ Open. 2022 Mar 30;12(3):e056282. doi: 10.1136/bmjopen-2021-056282.
- Individual participant dataSharing planned: Yes. IPD will be available upon reasonable request. The study protocol will be submitted for publication in a peer reviewed journal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Louise Smit contact
Adriaan Kooy, Dr. principal investigator
BDRC
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin TEVA 850 mg in people with Gestational Diabetes and Insulin Resistance, run by Bethesda Diabetes Research Center at 4 sites in Netherlands.
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 5 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 10 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Adriaan Kooy, Dr (+31528286859, a.kooy@treant.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GDM Outcome Score (GOS) in Phase A (time frame: 30 months). The study lists 3 primary outcomes in all. 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 NCT02947503, which also lists 1 linked publication.
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 10 Feb 2022.