Pregnancy Outcomes: Effects of Metformin Study (POEM Study)

NCT02947503 | Recruiting Phase 3 DMC

• 1 other identifier: NL 2016 POEMS
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 4

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.

Conditions

Gestational Diabetes; Insulin Resistance

Keywords

Gestational Diabetes; Insulin Resistance; Metformin; Hyperinsulinaemia; Prevention of Complications; Long Term Study; Mother and Child; Health Benefits

Outcome Measures

Primary Outcomes (3)

• GDM Outcome Score (GOS) in Phase A

  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.

  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

  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

  282 months

Secondary Outcomes (4)

• Secondary Outcome measures phase A mother

  30 months

• Secondary Outcome measures phase A child

  30 months

• Secondary outcome measures phase B

  42 months

• Secondary outcome measures phase C

  282 months

Study Arms (2)

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.

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.

Interventions

Metformin TEVA 850 mg DRUG

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.

Also known as: Metformin

Metformin on top of usual care

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Diabetes mellitus before pregnancy, except previous GDM
• Proteinuria: Urine Albumin-to-Creatinine Ratio (UACR) \> 35 mg/mmol at screening
• 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
• Ruptured membranes
• Multiple pregnancy
• Inability to understand or read the Dutch language
• Bariatric surgery in medical history
• Hyperemesis gravidarum

Sponsors & Collaborators

• Bethesda Diabetes Research Center: lead
• Maastricht University Medical Center: collaborator
• University Medical Center Groningen: collaborator
• Frisius Medisch Centrum: collaborator
• Martini Hospital Groningen: collaborator
• Treant Zorggroep: collaborator
• Nij Smellinghe Hosptial: collaborator

Study Sites (4)

Martini hospital Groningen

Groningen, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Treant Zorggroep

Hoogenveen, Emmen, Stadskanaal, Netherlands

RECRUITING

Medical Center Leeuwarden

Leeuwarden, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 35354633 DERIVED

MeSH Terms

Conditions

Diabetes, Gestational; Insulin Resistance; Hyperinsulinism

Interventions

Metformin

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Adriaan Kooy, Dr.

  BDRC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adriaan Kooy, Dr

CONTACT

+31528286859; a.kooy@treant.nl

Louise Smit

CONTACT

l.ismit@treant.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2016
• First Posted: October 28, 2016
• Study Start: November 26, 2019
• Primary Completion (Estimated): December 1, 2043
• Study Completion (Estimated): December 1, 2043
• Last Updated: February 10, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Within one year
• Access Criteria: Access to detailed information and IPD will be upon request. The PI and project team will evaluate the request based on the submission of an official request with details on what, why and how.

Locations

NL (4)