<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02980276</url>
  </required_header>
  <id_info>
    <org_study_id>NUIG-2016-01</org_study_id>
    <nct_id>NCT02980276</nct_id>
  </id_info>
  <brief_title>A Randomized Placebo Controlled Trial of the Effectiveness of Metformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects</brief_title>
  <acronym>EMERGE</acronym>
  <official_title>A Randomised Placebo Controlled Trial of the Effectiveness of Early MEtformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects (EMERGE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University of Ireland, Galway, Ireland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Health Research Board, Ireland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>HRB Clinical Research Facility Galway, Ireland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College Hospital Galway</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Portiuncula University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital of Limerick</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Maternity Hospital Limerick</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinical Research Support Unit, University of Limerick</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National University of Ireland, Galway, Ireland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective of the EMERGE trial is to determine whether metformin + usual care,&#xD;
      compared to placebo + usual care (introduced at the time of initial diagnosis of GDM),&#xD;
      reduces a) the need for insulin use, or hyperglycemia (primary outcome measure); b) excessive&#xD;
      maternal weight gain; c) maternal and neonatal morbidities and, d) cost of treatment for&#xD;
      women with Gestational Diabetes Mellitus.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 6, 2017</start_date>
  <completion_date type="Actual">April 13, 2023</completion_date>
  <primary_completion_date type="Actual">January 12, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin Initiation/Fasting Glucose</measure>
    <time_frame>Change from Gestational Weeks 32 and 38</time_frame>
    <description>The primary efficacy outcome is a composite of:&#xD;
Insulin initiation (Yes/No)&#xD;
Fasting glucose value &lt;/=5.1 mmol/l and &gt;5.1 mmol/l</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Insulin Initiation and Insulin Dose Required</measure>
    <time_frame>Time to Insulin Initiation, from date of randomization until the date delivery, assessed up to 40 weeks</time_frame>
    <description>Time to Insulin Initiation, from date of randomization until the date delivery, assessed up to 40 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal Morbidity at Delivery</measure>
    <time_frame>Delivery</time_frame>
    <description>Number of women with maternal morbidity at delivery that is related to treatment (e.g. hypertensive disorders, antepartum/postpartum haemorrhage, polyhydramnios)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mode of Delivery</measure>
    <time_frame>Delivery</time_frame>
    <description>Mode of delivery (e.g. vaginal, cesarean)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of Delivery</measure>
    <time_frame>Delivery</time_frame>
    <description>Gestational weeks at delivery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postpartum glucose status, insulin resistance, and metabolic syndrome</measure>
    <time_frame>12 weeks post-partum</time_frame>
    <description>Number of women with abnormal glucose values/insulin resistance/metabolic syndrome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-partum BMI</measure>
    <time_frame>12 weeks post-partum</time_frame>
    <description>Post-partum BMI in kg/m2 in participants between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infant Birth Weight</measure>
    <time_frame>Delivery</time_frame>
    <description>Weight in kg at birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal height and head circumference at delivery</measure>
    <time_frame>Delivery</time_frame>
    <description>Height in cm Head circumference in cm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal morbidities</measure>
    <time_frame>Delivery</time_frame>
    <description>Number of neonates with respiratory distress, jaundice, congenital anomalies, Apgar score, need for neonatal care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal hypoglycaemia</measure>
    <time_frame>Delivery</time_frame>
    <description>Number of neonates with glucose &lt;2.6mmol/l</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neonatal hypoglycaemia</measure>
    <time_frame>12 weeks post-partum</time_frame>
    <description>Number of neonates with glucose &lt;2.6mmol/l</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Acceptability</measure>
    <time_frame>4 weeks post-partum</time_frame>
    <description>Treatment acceptability determined by Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Rowan Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (EQ5D-5L)</measure>
    <time_frame>Treatment week 12</time_frame>
    <description>Quality of Life determined by EQ5D-5L Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post partum waist circumference</measure>
    <time_frame>12 weeks post partum</time_frame>
    <description>waist circumference in cm in participants between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gestational weight gain</measure>
    <time_frame>Change in weight from 24 weeks gestation until last visit before delivery</time_frame>
    <description>Change in weight (kg) from 24 weeks gestation until last visit before delivery</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Cost effectiveness and budget impact of metformin treatment in addition to standard care</measure>
    <time_frame>24 weeks gestation to 12 weeks post-partum</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">535</enrollment>
  <condition>Gestational Diabetes</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants randomised to the treatment arm will receive active metformin in addition to standard care. Metformin tablets will be titrated according to a dosing schedule to achieve the pre-specified glucose targets. Tablets will be in 500mg doses and will commence at 1 tablet per day (500mg) increasing to a maximum of 5 tablets per day (2500mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomised to the placebo arm will receive placebo in addition to standard care. Placebo will be titrated according to the dosing schedule to achieve the pre-specified glucose targets. Placebo tablets will commence at 1 tablet per day and will be increased to a maximum of 5 tablets per day over 10 days as with the treatment group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin Hydrochloride</intervention_name>
    <description>Women randomised to the metformin group will receive metformin 500mg once daily, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of 2500mg Metformin daily (5 tablets) or maximum tolerated dose, in addition to usual care (exercise and MNT), and taken until delivery.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Women randomised to the placebo group will receive 1 placebo tablet once daily, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of five placebo tablets daily, in addition to usual care (exercise and MNT), and taken until delivery.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to provide written informed consent&#xD;
&#xD;
          2. Participants aged 18-50&#xD;
&#xD;
          3. Pregnancy gestation up to 28 weeks (+ 6 days) confirmed by positive pregnancy test&#xD;
&#xD;
          4. Singleton pregnancy as determined by scan&#xD;
&#xD;
          5. Positive diagnosis of Gestational Diabetes Mellitus on a Oral Glucose Tolerance Test&#xD;
             (OGTT) according to the International Association of the Diabetes and Pregnancy Study&#xD;
             Groups (IADPSG) criteria if any one of the following are achieved: i) Fasting glucose&#xD;
             &gt;/= 5.1mmol/l and &lt;7mmol/l, or ii) 1 hour post glucose load of &gt;/=10mmol/l, or iii) 2&#xD;
             hour post glucose load of &gt;/=8.5 mmol/l and &lt;11.1mmo/l&#xD;
&#xD;
          6. Resident in the locality and intending to deliver within the trial site&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants who have an established diagnosis of diabetes (Type 1, Type 2, Monogenic&#xD;
             or secondary)&#xD;
&#xD;
          2. Participants with a fasting glucose &gt; 7mmol/l or a 2h value &gt; 11.1 mmol/l&#xD;
&#xD;
          3. Multiple pregnancies (twins, triplets etc.) as determined by scan&#xD;
&#xD;
          4. Known intolerance to metformin&#xD;
&#xD;
          5. Known contraindication to the use of metformin which include: i) renal insufficiency&#xD;
             (defined as serum creatinine of greater than 130 µmol/L or creatinine clearance &lt;60&#xD;
             ml/min), ii) moderate to severe liver dysfunction (aspartate aminotransferase (AST)&#xD;
             and alanine aminotransferase (ALT) greater than 3 times the upper limit of normal,&#xD;
             iii) shock or sepsis, and iv) previous hypersensitivity to metformin&#xD;
&#xD;
          6. Major congenital malformations or an abnormally deemed unsuitable for metformin by the&#xD;
             site PI or attending consultant&#xD;
&#xD;
          7. Known small for gestational age (Small for gestational age (SGA) refers to foetal&#xD;
             growth less than the 10th percentile (RCOG, 2014), or if foetal growth is deemed&#xD;
             unsatisfactory by the treating obstetrician)&#xD;
&#xD;
          8. Known gestational hypertension or pre-eclampsia or ruptured membranes&#xD;
&#xD;
          9. Participants who have a history of drug or alcohol use that, in the opinion of the&#xD;
             investigator, would interfere with adherence to study requirements&#xD;
&#xD;
         10. Participants with significant gastrointestinal problems such as severe vomiting,&#xD;
             Crohn's disease or colitis which will inadvertently affect absorption of the study&#xD;
             drug&#xD;
&#xD;
         11. Participants with congestive heart failure or history of congestive heart failure&#xD;
&#xD;
         12. Participants with serious mental illness which would affect adherence to study&#xD;
             medication or compliance with study protocol in the opinion of the investigator&#xD;
&#xD;
         13. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase&#xD;
             deficiency or glucose-galactose malabsorption&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Prof. Fidelma Dunne</last_name>
    <role>Principal Investigator</role>
    <affiliation>National University of Ireland, Galway, Ireland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Portiuncula University Hospital</name>
      <address>
        <city>Ballinasloe</city>
        <state>Galway</state>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Galway</name>
      <address>
        <city>Galway</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 9, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>August 11, 2023</last_update_submitted>
  <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National University of Ireland, Galway, Ireland</investigator_affiliation>
    <investigator_full_name>Fidelma Dunne</investigator_full_name>
    <investigator_title>Prof. Fidelma Dunne</investigator_title>
  </responsible_party>
  <keyword>Gestational Diabetes</keyword>
  <keyword>Diabetes</keyword>
  <keyword>Pregnancy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes, Gestational</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02980276
org study id: NUIG-2016-01
nct id: NCT02980276
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The overall objective of the EMERGE trial is to determine whether metformin + usual care,
      compared to placebo + usual care (introduced at the time of initial diagnosis of GDM),
      reduces a) the need for insulin use, or hyperglycemia (primary outcome measure); b) excessive
      maternal weight gain; c) maternal and neonatal morbidities and, d) cost of treatment for
      women with Gestational Diabetes Mellitus.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Insulin Initiation/Fasting Glucose
time frame: Change from Gestational Weeks 32 and 38
description: The primary efficacy outcome is a composite of:
Insulin initiation (Yes/No)
Fasting glucose value </=5.1 mmol/l and >5.1 mmol/l
measure: Time to Insulin Initiation and Insulin Dose Required
time frame: Time to Insulin Initiation, from date of randomization until the date delivery, assessed up to 40 weeks
description: Time to Insulin Initiation, from date of randomization until the date delivery, assessed up to 40 weeks
measure: Maternal Morbidity at Delivery
time frame: Delivery
description: Number of women with maternal morbidity at delivery that is related to treatment (e.g. hypertensive disorders, antepartum/postpartum haemorrhage, polyhydramnios)
measure: Mode of Delivery
time frame: Delivery
description: Mode of delivery (e.g. vaginal, cesarean)
measure: Time of Delivery
time frame: Delivery
description: Gestational weeks at delivery
measure: Postpartum glucose status, insulin resistance, and metabolic syndrome
time frame: 12 weeks post-partum
description: Number of women with abnormal glucose values/insulin resistance/metabolic syndrome
measure: Post-partum BMI
time frame: 12 weeks post-partum
description: Post-partum BMI in kg/m2 in participants between groups
measure: Infant Birth Weight
time frame: Delivery
description: Weight in kg at birth
measure: Neonatal height and head circumference at delivery
time frame: Delivery
description: Height in cm Head circumference in cm
measure: Neonatal morbidities
time frame: Delivery
description: Number of neonates with respiratory distress, jaundice, congenital anomalies, Apgar score, need for neonatal care unit
measure: Neonatal hypoglycaemia
time frame: Delivery
description: Number of neonates with glucose <2.6mmol/l
measure: Neonatal hypoglycaemia
time frame: 12 weeks post-partum
description: Number of neonates with glucose <2.6mmol/l
measure: Treatment Acceptability
time frame: 4 weeks post-partum
description: Treatment acceptability determined by Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Rowan Questionnaire
measure: Quality of Life (EQ5D-5L)
time frame: Treatment week 12
description: Quality of Life determined by EQ5D-5L Questionnaire
measure: Post partum waist circumference
time frame: 12 weeks post partum
description: waist circumference in cm in participants between groups
measure: Gestational weight gain
time frame: Change in weight from 24 weeks gestation until last visit before delivery
description: Change in weight (kg) from 24 weeks gestation until last visit before delivery
measure: Cost effectiveness and budget impact of metformin treatment in addition to standard care
time frame: 24 weeks gestation to 12 weeks post-partum
arm group label: Treatment
arm group type: Active Comparator
description: Participants randomised to the treatment arm will receive active metformin in addition to standard care. Metformin tablets will be titrated according to a dosing schedule to achieve the pre-specified glucose targets. Tablets will be in 500mg doses and will commence at 1 tablet per day (500mg) increasing to a maximum of 5 tablets per day (2500mg).
arm group label: Control
arm group type: Placebo Comparator
description: Participants randomised to the placebo arm will receive placebo in addition to standard care. Placebo will be titrated according to the dosing schedule to achieve the pre-specified glucose targets. Placebo tablets will commence at 1 tablet per day and will be increased to a maximum of 5 tablets per day over 10 days as with the treatment group.
intervention type: Drug
intervention name: Metformin Hydrochloride
description: Women randomised to the metformin group will receive metformin 500mg once daily, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of 2500mg Metformin daily (5 tablets) or maximum tolerated dose, in addition to usual care (exercise and MNT), and taken until delivery.
arm group label: Treatment
intervention type: Other
intervention name: Placebo
description: Women randomised to the placebo group will receive 1 placebo tablet once daily, with the dose titrated upwards every 2 days over 10 days increasing to a maximum of five placebo tablets daily, in addition to usual care (exercise and MNT), and taken until delivery.
arm group label: Control
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Prof. Fidelma Dunne
role: Principal Investigator
affiliation: National University of Ireland, Galway, Ireland
facility: 
facility: 
country: Ireland
responsible party type: Principal Investigator
investigator affiliation: National University of Ireland, Galway, Ireland
investigator full name: Fidelma Dunne
investigator title: Prof. Fidelma Dunne
mesh term: Diabetes, Gestational
mesh term: Diabetes Mellitus
mesh term: Metformin
sharing ipd: No