Early Screening for Gestational Diabetes Mellitus in a Low Risk Population (EaGeR)

November 21, 2024 updated by: National University Hospital, Singapore
This new feasibility pilot study aims to refine the design and protocols for a larger trial that will investigate the potential benefits of early oral glucose tolerance test (OGTT) screening in a population traditionally defined as low-risk for development of gestational diabetes. The study will evaluate its potential effectiveness in reducing the risks of neonatal morbidity/mortality and obstetric complications. Additionally, a machine learning algorithm to predict gestational diabetes mellitus (GDM) risk based on routinely obtained clinical information at pregnancy booking, and minimally invasive methods, such as continuous glucose monitoring (CGM) and gingival crevicular fluid (GCF) sampling, are being explored to predict the risk of hyperglycaemia. This study aims to investigate the utility of early pregnancy screening to enable timely detection and management of early gestational diabetes development in a low-risk population, ultimately promoting better health outcomes for mothers and their babies.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The Early Screening for Gestational Diabetes Mellitus in a Low-Risk Population (EaGeR) pilot study aims to inform a future trial that would evaluate whether early oral glucose tolerance test (OGTT) screening can improve pregnancy and neonatal outcomes among low-risk pregnant women in Singapore, a country that has one of the highest global incidences of gestational diabetes mellitus (GDM). GDM is associated with higher risks of neonatal and obstetric complications in the short-term, and in the long-term increased cardiometabolic risks in both mothers and their children.

The current local GDM screening practice comprises universal screening of all pregnancies (without pre-existing diabetes) with an OGTT around 24-28 weeks' gestation, and only offering early pregnancy screening to women with traditional high-risk factors for GDM development. The issue is that around 70% of diagnosed GDM cases in Singapore do not possess traditional high-risk factors, and they could have been potentially picked up earlier in gestation, if screened. Conversely, many women identified as high-risk in early pregnancy show normal glucose concentrations in an OGTT when screened in early gestation and when re-screened at 24-28 weeks. This study builds on findings from previous trials, which showed that early screening and treatment of mild glucose intolerance in high-risk women can reduce neonatal complications. The EaGeR Trial seeks to determine whether similar benefits can be achieved in an apparently low-risk Asian population.

This pilot study will recruit 120 low-risk pregnant women before 16 weeks' gestation. All participants will undergo an early OGTT before 16 weeks' and be randomly assigned to one of two arms: the experimental arm, where early OGTT results are revealed and immediate follow-up actions taken if GDM is diagnosed using the WHO 2013 criteria, and the control arm, where early OGTT results are concealed, with follow-up in accordance with standard care involving the routine OGTT screen at 24-28 weeks' gestation.

Data will be collected from the medical records to evaluate the primary and secondary outcomes which include pregnancy and neonatal events, as well as infant measures. Additionally, maternal symptoms and biomarkers, infant anthropometry and breastfeeding will be evaluated. Outcomes will be compared between study arms.

Further, the study will also test the utility of a newly developed machine learning algorithm as a novel and non-invasive method which uses clinical factors available at pregnancy booking to assess individual risk for GDM development. It will also explore the utility of other minimally invasive methods of continuous glucose monitoring (CGM) and gingival crevicular fluid (GCF) sampling at an early stage of pregnancy, in predicting the risk of GDM development.

This initial pilot study will help to refine the design and protocols of the definitive EaGeR Trial which will eventually guide the development of the optimal screening strategy for GDM among low-risk pregnant women in Singapore for improved neonatal and obstetric outcomes.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Singapore
      • Singapore, Singapore, 119228
        • National University Hospital
        • Contact:
        • Principal Investigator:
          • Shiao-Yng Chan, MBBChir (UK), FRCOG (UK), PhD
        • Sub-Investigator:
          • Karen Lim, MBBS, MRCOG, MMED, MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Pregnant women aged 21-39 years at recruitment
  2. Singleton pregnancy
  3. Less than 16 weeks pregnant at recruitment
  4. Intend to receive antenatal care and give birth at the National University Hospital

Exclusion Criteria:

  1. Known pre-existing type 1 or type 2 diabetes mellitus at recruitment

  2. Classified as high-risk for GDM at pregnancy booking using the traditional checklist:

    2.1) Age ≥40 years 2.2) Overweight/obese, i.e., body mass index (BMI) ≥25.0 kg/m2 2.3) First degree relative with diabetes mellitus 2.4) Previously delivered a baby ≥4 kg 2.5) Previously diagnosed with GDM 2.6) Impaired glucose tolerance (IGT) or impaired fasting glycaemia (IFG) on previous testing 2.7) Polycystic ovarian syndrome (PCOS) 2.8) Poor obstetric history (e.g. recurrent pregnancy loss, previous intrauterine death, congenital malformations) 2.9) History of chronic hypertension, hyperlipidaemia or cardiovascular disease 2.10) Glycosuria ≥ 2+ on urine dipstick

  3. Taking systemic steroid medication or metformin
  4. Participation in another intervention trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Early OGTT Results Revealed
The results of the early OGTT conducted before 16 weeks' gestation will be revealed to the participants. If the results indicate gestational diabetes mellitus (GDM) by the WHO 2013 criteria, immediate follow-up actions, including appropriate treatments, will be taken. Those with a normal result will undertake the universally offered routine OGTT at 24-28 weeks' gestation.
Diagnostic test: Early OGTT Results Revealed
Early pregnancy screening with a three-time point (fasting, 1h, 2h) 75g oral glucose tolerance test before 16 weeks' gestation with plasma glucose results revealed to the patient and clinician for appropriate management of any diabetes (gestational and type 2, if diagnosed) from early pregnancy onwards.
No Intervention: Early OGTT Results Concealed
Participants in this arm will undergo an early oral glucose tolerance test (OGTT) before 16 weeks' gestation, however, the results will be concealed from the participants and study investigators, and results will not be acted upon (unless they are suggestive of pre-existing type 2 diabetes mellitus as reviewed by an independent clinician, in which case appropriate follow-up will be arranged). All participants (except those with results suggestive of type 2 diabetes) will undertake the routine OGTT at 24-28 weeks' gestation, as per standard care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of perinatal/neonatal morbidity/mortality
Time Frame: At birth to one month postpartum
Display at least one of the following outcomes: preterm birth <37 weeks' gestation, large for gestational age neonate >90th centile of birthweight, birth trauma, shoulder dystocia, neonatal hypoglycaemia, neonatal respiratory distress, jaundice requiring phototherapy, stillbirth/neonatal death.
At birth to one month postpartum

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pre-eclampsia and hypertensive disorders of pregnancy
Time Frame: Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum
Number and proportion of participants who experience new onset hypertension in pregnancy, pre-eclampsia, eclampsia, or superimposed pre-eclampsia on chronic hypertension, with or without signs of progressive multi-system disorder or end-organ involvement, including cases of atypical pre-eclampsia where hypertension is not the predominant feature.
Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum
Antenatal and Peripartum obstetric events
Time Frame: Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum
Number and proportion of participants who experience antenatal complications, undergo caesarean section, suffer perineal trauma, experience postpartum haemorrhage, or require other delivery interventions, including labour induction, extended labour duration, use of oxytocin, instrumental delivery, and high dependency care.
Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum
Birthweight
Time Frame: At Birth
Raw birthweight, macrosomia defined as birthweight >4000g, low birthweight <2500g, Large for Gestational Age (>90th centile) and Small for Gestational Age (<10th centile) using customised/standardised birthweight references.
At Birth
Neonatal complications and treatments
Time Frame: From Birth to 3 months post-delivery
Admission to neonatal unit (including level of unit and length of stay), infant weight gain, hyperbilirubinaemia, infections, treatments (including antibiotics, iv/tube feeding, blood products, oxygen, breathing aids) and other neonatal conditions requiring medical care.
From Birth to 3 months post-delivery
Maternal depression and anxiety symptoms
Time Frame: Before 16 weeks' gestation, at around 24-28 weeks gestation (accepted up to 32 weeks and 6 days), postpartum (~1 month; accept 3-6 weeks post-delivery)
Scores of maternal depression and anxiety symptoms on validated questionnaires (Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 Scale). The scores on the Edinburgh Postnatal Depression Scale range from 0 to 30, with higher scores indicating more depression symptoms. The scores on the Generalized Anxiety Disorder-7 range from 0 to 21, where higher scores indicate more anxiety symptoms.
Before 16 weeks' gestation, at around 24-28 weeks gestation (accepted up to 32 weeks and 6 days), postpartum (~1 month; accept 3-6 weeks post-delivery)
Breastfeeding
Time Frame: Postpartum (~1 month; accept 3-6 weeks post-delivery)
Interviewer-administered questionnaire to evaluate the incidence and timing of skin-to-skin post-delivery, first suckle, duration of exclusivity of breastfeeding, and intake of formula feeds (timing of onset, duration, and frequency).
Postpartum (~1 month; accept 3-6 weeks post-delivery)
Prevalences of pre-existing diabetes mellitus and postpartum dysglycaemia (diabetes and pre-diabetes)
Time Frame: Oral glucose tolerance test (OGTT) before 16 weeks of gestation and at around 6-12 weeks postpartum
Pre-existing diabetes is identified based on glucose concentrations in a 75g OGTT defined by the World Health Organization (WHO) diagnostic criteria for non-pregnant adults. The following values are used to diagnose pre-existing diabetes: fasting glucose (0-hour): ≥ 7.0 mmol/L or 2-hour post-load glucose: ≥ 11.1 mmol/L. If either of these is met during the early pregnancy OGTT and post-partum OGTT (6-12 weeks post-delivery), the participant is diagnosed with pre-existing diabetes. Postpartum OGTT results will be obtained from medical records. Pre-diabetes postpartum will be identified by a 75g OGTT following the 2006 WHO criteria: Impaired fasting glucose (IFG) will be diagnosed when fasting plasma glucose (FPG) is between 6.1-6.9 mmol/L, while impaired glucose tolerance (IGT) will be defined by a 2-hour plasma glucose of 7.8-11.0 mmol/L.
Oral glucose tolerance test (OGTT) before 16 weeks of gestation and at around 6-12 weeks postpartum
Gestational diabetes incidence (early and late diagnosis)
Time Frame: Pregnancy Oral Glucose Tolerance Test (OGTT) before 16 weeks of gestation and/or at around 24-28 weeks of gestation (accept all results till 32 weeks and 6 days)
GDM is diagnosed based on criteria set by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and WHO (2013). If at least one plasma glucose value meet the following criteria during a 75g three time point OGTT, it will indicate GDM: fasting glucose: ≥ 5.1 mmol/L, 1-hour post-load glucose: ≥ 10.0 mmol/L or 2-hour post-load glucose: ≥ 8.5 mmol/L.
Pregnancy Oral Glucose Tolerance Test (OGTT) before 16 weeks of gestation and/or at around 24-28 weeks of gestation (accept all results till 32 weeks and 6 days)
Predictive performance of a novel machine-learning-derived algorithm
Time Frame: Up to 54 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)
A novel machine-learning-derived algorithm, specifically designed for the Singapore pregnant population, will use clinical data collected in early pregnancy (including maternal age, ethnicity, mean arterial blood pressure) to predict GDM development. The sensitivity, specificity, positive predictive and negative predictive value, receiver operating characteristic curve (ROC curve) will be evaluated for GDM and glucose intolerance as well as for pregnancy and neonatal outcomes.
Up to 54 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)
Continuous Glucose Monitor (CGM) Data Measurements and predictive performance
Time Frame: Up to 48 weeks, from recruitment up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)
Identification of the key metrics from CGM evaluation that predict GDM, glucose intolerance, later pregnancy/postpartum dysglycaemia, and pregnancy and neonatal outcomes.
Up to 48 weeks, from recruitment up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)
Gingival crevicular fluid (GCF) and circulating biomarkers
Time Frame: Up to 48 weeks, from recruitment up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)
Identification of the key biomarkers from metabolomic, proteomic, and transcriptomic analyses on gingival crevicular fluid samples and blood obtained in early pregnancy that associate with GDM and glucose intolerance, later pregnancy/postpartum dysglycaemia, and pregnancy and neonatal outcomes.
Up to 48 weeks, from recruitment up to the time of latest OGTT (32 weeks and 6 days gestation or OGTT at 6-12 weeks postpartum)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Collaborators

Agency for Science, Technology and Research
National University of Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2024

Primary Completion (Estimated)

April 30, 2026

Study Completion (Estimated)

November 30, 2026

Study Registration Dates

First Submitted

October 17, 2024

First Submitted That Met QC Criteria

November 21, 2024

First Posted (Estimated)

November 25, 2024

Study Record Updates

Last Update Posted (Estimated)

November 25, 2024

Last Update Submitted That Met QC Criteria

November 21, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023/00970

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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