Night Owl Metabolism

Night Owl Metabolism: Investigating the Impact of Chronotype on Glucose Metabolism in Youth

The proposed study uses a novel and rigorous randomized cross-over study design in youth (18-23y) 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.

Study Overview

• Status: Recruiting
• Conditions: Overweight; PreDiabetes; Impaired Glucose Tolerance
• Intervention / Treatment: Diagnostic test: Timing of OGTT; Behavioral: Timing of Standardized Meal

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Talia Hitt, MD/MPH/MSHP; Phone Number: 860-324-0072; Email: thitt2@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins School of Medicine
      • Contact: Talia Hitt, MD/MPH/MSHP; Phone Number: 860-324-0072; Email: thitt2@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort A - Late Chronotype first, then alternate; Sleep onset after 2am	Diagnostic test: Timing of OGTT; In Aim 1, timing of oral glucose tolerance test will be altered.; Behavioral: Timing of Standardized Meal; In Aim 2, timing of a standardized meal will be altered.
Other: Cohort B - Non-late Chronotype first, then alternate; Sleep onset before 11pm	Diagnostic test: Timing of OGTT; In Aim 1, timing of oral glucose tolerance test will be altered.; Behavioral: Timing of Standardized Meal; In Aim 2, timing of a standardized meal will be altered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-Hour Difference in Glucose	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.	Day 4 and Day 11 of Aim 1 derived from OGTT
Insulin Sensitivity (by Oral Minimal Model)	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.	Day 4 and Day 11 of Aim 1 derived from OGTT
2-hour Incremental Area Under the Curve (iAUC) for glucose	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.	Day 1 and Day 8 of Aim 2 during post-prandial period following each standardized meal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Fasting Glucose	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.	Day 4 and Day 11 of Aim 1 obtained before OGTT
Insulin secretion indices	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.	Day 4 and Day 11 of Aim 1 derived from OGTT
Incremental Area Under the Curve (iAUC) for Insulin	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.	Day 4 and Day 11 of Aim 1 derived from OGTT
Difference in Disposition Index	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.	Day 4 and Day 11 of Aim 1 derived from OGTT
Difference in Insulin Clearance	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.	Day 4 and Day 11 of Aim 1 derived from OGTT
Mean Glucose	Analysis of between group differences in mean glucose derived from continuous glucose monitor	Up to 8 days
Percent Time Spent Above 120 mg/dL	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)]	Up to 8 days
Percent Time Spent Above 140 mg/dL	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).	Up to 8 days
Number of Excursions greater than 140mg/dL	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).	Up to 8 days
Difference in Post-prandial peak	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	Day 1 and Day 8 of Aim 2 during post-prandial period following each standardized meal
Standard Deviation of Glucose	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).	Up to 8 days
Coefficient of Variation of Glucose	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).	Up to 8 days
Hemoglobin A1c levels	Analysis of between group differences in hemoglobin A1c levels	Day 4 of Aim 1 during first OGTT Visit

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); DexCom, Inc.; Lawson Wilkins Pediatric Endocrine Society
• Investigators: Principal Investigator: Talia Hitt, MD/MPH/MSHP, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): January 31, 2030

Study Registration Dates

• First Submitted: July 12, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: sleep; chronotype
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperglycemia; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Prediabetic State; Glucose Intolerance
• Other Study ID Numbers: IRB00428863

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No