Clinical trial NCT02947503: Pregnancy Outcomes: Effects of Metformin Study (POEM Study)
Official title: Pregnancy Outcomes: Effects of Metformin Study (POEM Study), a Long Term Randomized Controlled Study in Gestational Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Gestational Diabetes
Insulin Resistance
Keywords: Gestational Diabetes
Insulin Resistance
Metformin
Hyperinsulinaemia
Prevention of Complications
Long Term Study
Mother and Child
Health Benefits
Lead sponsor: Bethesda Diabetes Research Center
Sponsor class: OTHER
Collaborators: name: Maastricht University Medical Center
name: University Medical Center Groningen
name: Frisius Medisch Centrum
name: Martini Hospital Groningen
name: Treant Zorggroep
name: Nij Smellinghe Hosptial
First posted: 2016-10-28
Enrollment: 500
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: GDM Outcome Score (GOS) in Phase A
timeFrame: 30 months
measure: T2D and obesity at the end of Phase B
timeFrame: 42 months
measure: Development of T2D and obesity during Phase C
timeFrame: 282 months
Secondary outcomes:
measure: Secondary Outcome measures phase A mother
timeFrame: 30 months
measure: Secondary Outcome measures phase A child
timeFrame: 30 months
measure: Secondary outcome measures phase B
timeFrame: 42 months
measure: Secondary outcome measures phase C
timeFrame: 282 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Martini hospital Groningen
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Hoogenveen, Emmen, Stadskanaal
country: Netherlands
facility: Treant Zorggroep
city: Leeuwarden
country: Netherlands
facility: Medical Center Leeuwarden
Study officials:
affiliation: BDRC
name: Adriaan Kooy, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.