Night Owl Metabolism

Not Applicable

Recruiting

• Conditions: PreDiabetes; Overweight; Impaired Glucose Tolerance
• Interventions: Diagnostic Test: Timing of OGTT; Behavioral: Timing of Standardized Meal

• Registration Number: NCT06507722
• Lead Sponsor: Johns Hopkins University

Brief Summary

The proposed study uses a novel and rigorous randomized cross-over study design in youth (17-23y) with late and non-late chronotype (n=35 per group) to assess the glycemic effect of "aligning" an oral glucose tolerance test (OGTT) or first-meal of day to a subject's chronotype. Both groups will undergo 2 OGTTs (aligned and mis-aligned with chronotype) to compare glucose tolerance and insulin sensitivity within-subject (primary outcome) and between groups (Aim 1). Then, youth will also undergo two standardized meals (aligned and mis-aligned with chronotype) while wearing continuous glucose monitoring to compare post-prandial glucose excursions within-subject and between groups (Aim 2). A pilot Exploratory Aim 3 (n=12 per group) will investigate delayed melatonin patterns under dim-light as a potential pathophysiologic mechanism behind abnormal glucose tolerance in youth with late chronotype on morning OGTTs.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-07-12
• Study First Submitted QC: 2024-07-12
• Study First Posted: 2024-07-18
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-10
• Study Start: 2025-02-01
• Primary Completion: 2029-12-31
• Study Completion: 2030-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Overweight similar to (BMI ≥ 85th percentile but <95th percentile for age and sex per Centers for Disease Control and Prevention growth curves (as Centers for Disease Control and Prevention growth curves contain ages ≤ 20y; if ages 21-23 years, the BMI ≥ 85th and <95th percentile equivalents for a 20-year-old will be used))
• Post-pubertal
• Normal sleep duration (avg. >7 hours of sleep per night)
• Social jetlag (difference between weekend and weekday sleep) of < 2 hours.

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Exclusion Criteria

• Known diabetes, sleep disorders, major organ system illness, pregnancy, or genetic syndrome
• Medication use known to affect insulin sensitivity, glucose tolerance, or circadian rhythm
• Screening high risk for obstructive sleep apnea
• Night shift work.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cohort A - Late Chronotype first, then alternate	Timing of Standardized Meal	Sleep onset after 2am
Cohort B - Non-late Chronotype first, then alternate	Timing of Standardized Meal	Sleep onset before 11pm
Cohort A - Late Chronotype first, then alternate	Timing of OGTT	Sleep onset after 2am
Cohort B - Non-late Chronotype first, then alternate	Timing of OGTT	Sleep onset before 11pm

Primary Outcome Measures

Name	Time	Method
2-Hour Difference in Glucose	Day 4 and Day 11 of Aim 1 derived from OGTT	Within-subject difference in 2-hour glucose after glucose ingestion on OGTT between early and late OGTT (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late OGTT.
Insulin Sensitivity (by Oral Minimal Model)	Day 4 and Day 11 of Aim 1 derived from OGTT	Within-subject difference in insulin sensitivity (derived from oral Minimal Model) between early and late OGTT (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late OGTT.
2-hour Incremental Area Under the Curve (iAUC) for glucose	Day 1 and Day 8 of Aim 2 during post-prandial period following each standardized meal	Within-subject difference in iAUC for glucose from continuous glucose monitor between early and late Meal (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late Meal.

Secondary Outcome Measures

Name	Time	Method
Difference in Disposition Index	Day 4 and Day 11 of Aim 1 derived from OGTT	Within-subject difference in disposition index (derived from insulin sensitivity and insulin secretion metrics) between early and late OGTT (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late OGTT.
Difference in Post-prandial peak	Day 1 and Day 8 of Aim 2 during post-prandial period following each standardized meal	Within-subject difference in post-prandial peak from continuous glucose monitor between early and late Meal (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late Meal
Difference in Fasting Glucose	Day 4 and Day 11 of Aim 1 obtained before OGTT	Within-subject difference in fasting glucose at start of OGTT between early and late OGTT (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late OGTT.
Insulin secretion indices	Day 4 and Day 11 of Aim 1 derived from OGTT	Within-subject difference in insulin secretion (dynamic phase, static phase, total and insulin secretory rate) from c-peptide minimal model between early and late OGTT (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late OGTT.
Mean Glucose	Up to 8 days	Analysis of between group differences in mean glucose derived from continuous glucose monitor
Number of Excursions greater than 140mg/dL	Up to 8 days	Analysis of between group differences in the number of excursions above 140 mg/dL derived from continuous glucose monitor. Over course of wearing continuous glucose monitor for Aim 2 (8 days).
Incremental Area Under the Curve (iAUC) for Insulin	Day 4 and Day 11 of Aim 1 derived from OGTT	Within-subject difference in iAUC for insulin after glucose ingestion between early and late OGTT (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late OGTT.
Hemoglobin A1c levels	Day 4 of Aim 1 during first OGTT Visit	Analysis of between group differences in hemoglobin A1c levels
Difference in Insulin Clearance	Day 4 and Day 11 of Aim 1 derived from OGTT	Within-subject difference in insulin clearance (derived from Watanabe et al. model) between early and late OGTT (primary analysis) in the late chronotype group and secondary analysis will be between group differences between early and late OGTT.
Coefficient of Variation of Glucose	Up to 8 days	Analysis of between group differences in coefficient of variation of glucose derived from continuous glucose monitor. Over course of wearing continuous glucose monitor for Aim 2 (8 days).
Percent Time Spent Above 120 mg/dL	Up to 8 days	Analysis of between group differences in time spent above 120 mg/dL derived from continuous glucose monitor. Over course of wearing continuous glucose monitor for Aim 2 (8 days)\]
Percent Time Spent Above 140 mg/dL	Up to 8 days	Analysis of between group differences in time spent above 140 mg/dL derived from continuous glucose monitor. Over course of wearing continuous glucose monitor for Aim 2 (8 days).
Standard Deviation of Glucose	Up to 8 days	Analysis of between group differences in standard deviation of glucose derived from continuous glucose monitor. Over course of wearing continuous glucose monitor for Aim 2 (8 days).

Trial Locations

Locations (1)

Johns Hopkins School of Medicine; 🇺🇸 Baltimore, Maryland, United States