Night Owl Metabolism
NCT Number: NCT06507722
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: PreDiabetes|Overweight|Impaired Glucose Tolerance
Interventions: DIAGNOSTIC_TEST: Timing of OGTT|BEHAVIORAL: Timing of Standardized Meal
Sponsor: Johns Hopkins University
Collaborators: Lawson Wilkins Pediatric Endocrine Society|National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sex: ALL
Age: ADULT
Enrollment: 70
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: DOUBLE (INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-09-01
Completion Date: 2030-01-31
Locations: Johns Hopkins School of Medicine, Baltimore, Maryland, 21287, United States

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.

Primary Outcome Measures: 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: 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|Hemoglobin A1c levels, Analysis of between group differences in hemoglobin A1c levels, Day 4 of Aim 1 during first OGTT Visit|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