Influence of Circadian Clock on Hormonal, Metabolic, Neurocognitive Markers in Adolescents With and Without Diabetes

Influence of Circadian Clock on Diurnal Dietary Intake, Glucose Variability, Time Spent in Range, and Neuro-cognitive Achievements Among Adolescents With and Without Type 1 Diabetes

Type 1 diabetes mellitus (T1DM), makes its appearance during childhood and youth, but management implications last till late adulthood. Its treatment includes the combination of multiple daily glucose measurements, insulin administration and balanced nutrition. The goals of therapy are to achieve glycemic control (HbA1c < 7.5%), and minimal glycemic excursions. Furthermore, recent studies imply that keeping HbA1c within target range is not sufficient to prevent complications, attributed mainly to blood glucose level fluctuating from high to low, associated with food intake and adolescents behavior. The current implication of glycemic control on the central nervous system (CNS) includes abnormal electrical brain activity, structural changes in brain's white and grey matter, and cognitive impairment. Still, little is known on the effect of sleep pattern, including circadian rhythm reversal ("biological clock) on asymptomatic glycemic excursions, and on CNS functions. There is no data regarding the association of the biologic clock on CNS functionality among adolescents, nonetheless among T1DM adolescents, for whom behavior and circadian rhythm alterations may have harmful effect. The investigators propose a cross-over designed study by examining adolescents with and without T1DM during 2 weeks of regular sleeping pattern (night sleep), and during 2 weeks of sleeping during the day as happens during summer vacation. The main objective of the proposed study is to offer proof of the clinical and metabolic relevance and cognitive effects of the reversal of the circadian clock in adolescents with and T1DM during summer vacations and weekends. Study is designed to demonstrate a difference among healthy and diabetics during reversed night/day circadian clocks in the time spent within target range of glucose, performance on neuro cognitive tasks, electrical brain activity, and hormonal profile.

Study Overview

• Status: Not yet recruiting
• Conditions: ADHD; Memory Impairment; T1DM; Sleep Disorders, Circadian Rhythm
• Intervention / Treatment: Behavioral: Normal Circadian Rhythm; Behavioral: Reversed Circadian Rhythm

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Marianna Rachmiel, M.D; Phone Number: +972-537346636; Email: rmarianna@gmail.com
• Study Contact Backup: Name: Avital Leshem; Phone Number: +972-528303012; Email: childendo.research@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patiets ages 12-18 years with type 1 diabetes mellitus and healthy controls same age and gender distribution

Description

Inclusion Criteria:

• Families living in areas with high access to medical care.
• Age: 12-18 years old
• T1D diagnosis for longer than 1 year
• speaking fluent Hebrew

Exclusion Criteria:

• significant renal or liver function abnormalities
• head injuries,
• epileptic episodes
• psychiatric medications
• lack of Hebrew abilities
• disagreement to comply with all the study requests
• history of more than one episode of a severe hypoglycemic event in the past, including loss of consciousness or more than one episode of diabetic ketoacidosis.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal Circardian rhythm; Regular night sleep, with at least 7 hours length of sleep.	Behavioral: Normal Circadian Rhythm; Normal day/ night sleep cycle
Reversed circadian rhythm; Night/day circadian clock is opposite, with at least 7 hours length of sleep	Behavioral: Reversed Circadian Rhythm; Revered day/ night sleep cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Affects of reversal circadian clock on neuro cognitive tasks performance among healthy and T1D patients, according to glucose	Score of neurocognitive tests for executive function according to day/night sleeping pattern session	2 years
Affects of reversal circadian clock on Glucose Variability parameters among both healthy and T1DM adolescents .	Time spent in range of glucose of 70-180 mg/dl according to day/night sleeping pattern	2 years
Affects of reversal circadian clock on sleep quality among both healthy and T1DM adolescents (mainly T1DM), controlled for BMI-SDS, and mean HbA1c in T1D patients.	Quality of sleep according to PSQI, according to day/night sleeping pattern	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Melatonin profile according to night/day sleep cycle among healthy and among T1D patients	Differences in levels of melatonin in nmol/l between sessions and between health and T1D patients	2 years
Temperature according to night/day sleep cycle among healthy and among T1D patients	Differences in peripheral body temperature (celzius) between sessions and between health and T1D patients	2 years
EEG registration in accordance with the circadian curve and neurocognitive achievements	Power of high frequency amplitude between night/sleep sessions among T1D and healthy	2 years
MRI structural changes	DT1-MRI trajectoris areas of supra-chiasmatic nuclei sleeping pattern session	2 years
Hormonal profile according to night/day sleep cycle among healthy and among T1D patients	Differences in levels of cortisol in nmol/l between sessions and between health and T1D patients	2 years
Metabolic parameters according to night/day sleep cycle among healthy and among T1D patients	Differences in blood pressure (mmHG) between sessions and between health and T1D patients	2 years

Collaborators and Investigators

• Sponsor: Assaf-Harofeh Medical Center
• Collaborators: Hadassah Medical Organization; Western University, Canada

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 1, 2026
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: May 26, 2019
• First Submitted That Met QC Criteria: August 10, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): May 26, 2020
• Last Update Submitted That Met QC Criteria: May 22, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Pediatrics; T1DM; Hypothalamus; Glucose variability; CORTICAL BRAIN; Biological clock
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Neurologic Manifestations; Occupational Diseases; Chronobiology Disorders; Sleep Wake Disorders; Sleep Disorders, Circadian Rhythm
• Other Study ID Numbers: 0291-18

Drug and device information, study documents

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