Clinical trial NCT06704035: Early Screening for Gestational Diabetes Mellitus in a Low Risk Population
Official title: Early Screening for Gestational Diabetes Mellitus in a Low Risk Population
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Gestational Diabetes Mellitus (GDM)
Glucose Intolerance During Pregnancy
Keywords: Early screening
Gestational diabetes
Oral glucose tolerance test (OGTT)
Neonatal complications
Pregnancy complications
Machine learning algorithm
Continuous glucose monitoring (CGM)
Gingival crevicular fluid (GCF)
IADPSG criteria
WHO 2013 gestational diabetes criteria
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: National University of Singapore
name: Agency for Science, Technology and Research
First posted: 2024-11-25
Enrollment: 120
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Classic two parallel arm study in a 1:1 ratio. Participants will be assigned at random using a computerised database to either an experimental group (early "OGTT Results Revealed"), or a control group (early "OGTT Results Concealed"). The investigators, healthcare providers and participants will know which study arm they are allocated to, but the early OGTT results will only be made known for the "OGTT Results Revealed" group.
Primary purpose: SCREENING

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite of perinatal/neonatal morbidity/mortality
timeFrame: At birth to one month postpartum
Secondary outcomes:
measure: Pre-eclampsia and hypertensive disorders of pregnancy
timeFrame: Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum
measure: Antenatal and Peripartum obstetric events
timeFrame: Up to 49 weeks, from the estimated date of conception (based on menstrual and ultrasound scan data) up to 6 weeks postpartum
measure: Birthweight
timeFrame: At Birth
measure: Neonatal complications and treatments
timeFrame: From Birth to 3 months post-delivery
measure: Maternal depression and anxiety symptoms
timeFrame: 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)
measure: Breastfeeding
timeFrame: Postpartum (~1 month; accept 3-6 weeks post-delivery)
measure: Prevalences of pre-existing diabetes mellitus and postpartum dysglycaemia (diabetes and pre-diabetes)
timeFrame: Oral glucose tolerance test (OGTT) before 16 weeks of gestation and at around 6-12 weeks postpartum
measure: Gestational diabetes incidence (early and late diagnosis)
timeFrame: 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)
measure: Predictive performance of a novel machine-learning-derived algorithm
timeFrame: 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)
measure: Continuous Glucose Monitor (CGM) Data Measurements and predictive performance
timeFrame: 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)
measure: Gingival crevicular fluid (GCF) and circulating biomarkers
timeFrame: 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)
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
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