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Pregnancy Outcomes: Effects of Metformin Study (POEM Study) (POEM)

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ClinicalTrials.gov Identifier: NCT02947503
Recruitment Status : Not yet recruiting
First Posted : October 28, 2016
Last Update Posted : November 1, 2016
Sponsor:
Collaborators:
Maastricht University Medical Center
University Medical Center Groningen
Medical Centre Leeuwarden
Martini Hospital Groningen
UMC Utrecht
Information provided by (Responsible Party):
Bethesda Diabetes Research Center

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.

Condition or disease Intervention/treatment Phase
Gestational Diabetes Insulin Resistance Drug: Metformin HCL 850 CF Phase 3

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 two 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 two 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pregnancy Outcomes: Effects of Metformin Study (POEM Study), a Long Term Randomized Controlled Study in Gestational Diabetes
Study Start Date : January 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2040

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Metformin on top of usual care

Metformin HCL 850 CF (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 HCF 850 CF (1-3 times daily) on top of usual care.

Drug: Metformin HCL 850 CF
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.
Other Name: Metformin

No Intervention: Usual care

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.




Primary Outcome Measures :
  1. 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.

    GOS will be assessed in each patient according protocol by the investigator, monitored in detail by an independent Clinical Trial Service, and verified by an independent committee.


  2. T2D and obesity at the end of Phase B [ Time Frame: 42 months ]
    Diagnosis of T2D and/or obesity at the end of Phase B

  3. Development of T2D and obesity during Phase C [ Time Frame: 282 months ]
    Development of T2D and/or obesity on the long term during Phase C - long term observational in mother and child


Secondary Outcome Measures :
  1. Components of GOS in Phase A [ Time Frame: 30 months ]
    1. Maternal weight / weight gain, 2. change in body composition, 3. glycemic control, 4. proteinuria, 5. insulin treatment, 6. Maternal urinary tract infection , 7. Pre-eclampsia, / eclampsia / HELLP syndrome, 8 gestational hypertension 9. Maternal mortality, 10. Postpartum haemorrhage, 11 Thrombosis (in pregnancy and/or childbed).

  2. Components of GOS in Phase B [ Time Frame: 42 months ]
    1. Diabetes & prediabetes development; 2. Weight development 3. Hypertension development; 4. Thrombotic and CV incidents,

  3. Components of GOS in Phase C [ Time Frame: 282 months ]
    Development of any chronic disease



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  • Proteïnuria: 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02947503


Contacts
Contact: Adriaan Kooy, Dr +31528286859 a.kooy@treant.nl
Contact: Anita Faber, MSc +31528286678 a.faber@treant.nl

Sponsors and Collaborators
Bethesda Diabetes Research Center
Maastricht University Medical Center
University Medical Center Groningen
Medical Centre Leeuwarden
Martini Hospital Groningen
UMC Utrecht
Investigators
Principal Investigator: Adriaan Kooy, Dr. BDRC

Responsible Party: Bethesda Diabetes Research Center
ClinicalTrials.gov Identifier: NCT02947503     History of Changes
Other Study ID Numbers: NL 2016 POEMS
First Posted: October 28, 2016    Key Record Dates
Last Update Posted: November 1, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Bethesda Diabetes Research Center:
Gestational Diabetes
Insulin Resistance
Metformin
Hyperinsulinaemia
Prevention of Complications
Long Term Study
Mother and Child
Health Benefits

Additional relevant MeSH terms:
Diabetes, Gestational
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pregnancy Complications
Diabetes Mellitus
Endocrine System Diseases
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs