Early Pregnancy Lifestyle and Glucose Patterns: A Substudy of TOFFFY

Official title

Early-Pregnancy Chronobehavioural Profiles and Continuous Glucose Dynamics: A Nested Randomised Pilot Study of TOFFFY

Overview

The goal of this clinical trial is to examine how daily behavioral patterns in early pregnancy, including sleep, physical activity, and meal timing, influence continuous glucose dynamics and subsequent risk of gestational diabetes mellitus (GDM) in pregnant women without pre-existing diabetes. The main questions it aims to answer are: 1. Do early-pregnancy chronobehavioral patterns (e.g., irregular sleep, night eating, and unstable rest-activity rhythms) relate to continuous glucose patterns measured using continuous glucose monitoring (CGM)? 2. Can early behavioral and CGM-derived measures predict glucose regulation and metabolic outcomes later in pregnancy (24-28 weeks)? 3. Does real-time self-monitoring using wearable devices and food logging improve glycemic outcomes compared to usual care? This study is a prospective, nested randomized pilot trial embedded within the ongoing Towards Optimal Fertility, Fathering and Fatherhood studY (TOFFFY) cohort (NCT06293235) at KK Women's and Children's Hospital, Singapore. A total of 140 pregnant women without pre-existing diabetes, recruited at ≤13 weeks gestation, will be randomized in a 1:1 ratio to either a pilot arm (wearable-based self-monitoring) or a control arm (usual care). Participants in the pilot arm (n=70) will undergo intensive behavioral and metabolic monitoring over a 14-day period in early pregnancy, including continuous glucose monitoring using a CGM device, wrist actigraphy to assess sleep-wake and rest-activity patterns, and an AI-supported mobile application to record meal timing and dietary intake. Participants will have real-time access to their glucose data and behavioral feedback, enabling self-monitoring and potential behavioral adjustments.

Detailed description

Circadian disruption during pregnancy is increasingly recognized as an important, yet understudied, contributor to impaired glucose regulation and gestational diabetes mellitus (GDM). Emerging evidence suggests that nocturnal eating, irregular sleep timing, reduced rest-activity rhythm (RAR) stability, and greater behavioral variability may impair glucose homeostasis through pathways involving reduced insulin sensitivity, altered β-cell stress, and inflammation.

Most studies assess chronobehaviors using questionnaires, which are limited by recall bias and poor temporal granularity. Recent technological advances enable high-resolution measurement of circadian and metabolic physiology using wrist actigraphy and continuous glucose monitor (CGM). These tools allow objective quantification of sleep timing, RAR, activity fragmentation, and 24-hour glycaemic patterns. Integrating these data in early pregnancy may enable earlier identification of at-risk women, allowing intervention before the onset of overt hyperglycaemia.

The ongoing TOFFFY study (NCT 06293235) provides a unique opportunity to embed such a pilot study among well-phenotyped Singaporean pregnant women. Leveraging this cohort will support mechanistic insights into the interplay between circadian rhythms, meal timing, and glucose regulation, and provide preliminary data to power a larger mother-fetus chronometabolic project. Findings from this pilot will provide high-resolution insight into how early-pregnancy circadian, behavioral, and glycemic patterns interact to shape metabolic physiology. By capturing glucose responses such as glucose AUC, insulin resistance, and C-peptide, the study will identify early mechanistic pathways through which chronobehavioral disruption contributes to dysglycemia.

Interventions

• Device Continuous glucose monitor (CGM)
  Participants will wear a continuous glucose monitor for 14 days in early pregnancy.
• Device Wrist actigraphy device
  A wrist actigraphy device will be used to assess sleep-wake patterns and physical activity over 14 days.
• Behavioral AI-based dietary and meal timing logging mobile application
  Participants will record their dietary intake, meal timing logging, and feedback-based self-monitoring using an AI-based food logging mobile application.

Primary outcome measures

• 24-hour glucose area under the curve (AUC) [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Nocturnal glucose levels [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Glycemic variability - standard deviation (SD) [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Glycemic variability - coefficient of variation (CV) [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Rest-activity rhythm (RAR) - intra-daily variability (IV) [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Rest-activity rhythm (RAR) - inter-daily stability (IS) [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Chrononutrition behavior - meal timing [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Chrononutrition behavior - eating jetlag [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Chrononutrition behavior - frequency of night-eating [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]

Secondary outcome measures (8)

• Glucose tolerance status during pregnancy [Time frame: From 24 weeks till 28 weeks of gestation]
• Total glycemic exposure during pregnancy [Time frame: From 24 weeks till 28 weeks of gestation]
• Glycemic marker - fasting insulin [Time frame: From 24 weeks till 28 weeks of gestation]
• Glycemic marker - C-peptide [Time frame: From 24 weeks till 28 weeks of gestation]
• Maternal glycemic control index - Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) [Time frame: From 24 weeks till 28 weeks of gestation]
• Glycemic control index - Homeostatic Model Assessment for Beta Cell Function (HOMA-β) [Time frame: From 24 weeks till 28 weeks of gestation]
• Sleep timing [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]
• Physical activity level [Time frame: From enrollment in first trimester (≤13 weeks gestation), over 14 days]

Eligibility criteria

Inclusion criteria

• Enrolled in the Towards Optimal Fertility, Fathering and Fatherhood studY (TOFFFY) (NCT06293235)
• Females who are currently pregnant and with viable intrauterine pregnancy at ≤13 weeks gestation at enrolment

Exclusion criteria

• Females with pre-existing diabetes mellitus (Type 1 or Type 2) and/or chronic medical conditions affecting glucose metabolism
• Females who are taking medications known to significantly affect glucose metabolism
• Females with multiple pregnancy (e.g., twins or higher-order gestation)
• Females who are unable to comply with study procedures, including: Inability to use smartphone-based applications and inability to wear wrist actigraphy device

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Singapore · 1 center

• KK Women's and Children's Hospital — Singapore

Identifiers

NCT: NCT07534670 · 2024/2120

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗