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

Sponsor

Assaf-Harofeh Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04054934

Collaborator

Western University, Canada (Other), Hadassah Medical Organization (Other)

100

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
T1DM Sleep Disorders, Circadian Rhythm ADHD Memory Impairment	Behavioral: Reversed Circadian Rhythm Behavioral: Normal Circadian Rhythm

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Case-Crossover

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

Affects of reversal circadian clock on neuro cognitive tasks performance among healthy and T1D patients, according to glucose [2 years]
Score of neurocognitive tests for executive function according to day/night sleeping pattern session
Affects of reversal circadian clock on Glucose Variability parameters among both healthy and T1DM adolescents . [2 years]
Time spent in range of glucose of 70-180 mg/dl according to day/night sleeping pattern
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. [2 years]
Quality of sleep according to PSQI, according to day/night sleeping pattern

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.