Behavioral Chronotype: Impact on Sleep and Metabolism

Cardiovascular Diseases Clinical Trial

Official title:

Behavioral Chronotype: Impact on Sleep and Metabolism

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03647306
• Other study ID #: IRB17-1768
• Secondary ID: P01AG011412
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 2, 2018
• Est. completion date: January 1, 2027

Study information

• Verified date: May 2024
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine how the timing of eating changes how the body makes and uses energy (metabolism). This study will also examine if metabolism changes with age.

Description:

The timing of food intake and caloric distribution across the 24hr day are emerging as contributing factors to weight gain. The idea that not only what you eat, but when you eat can contribute to weight gain has garnered interest from both the scientific community and the public. In fact, the distribution of caloric intake over the 24hr day has been recently recognized as a potential source of "circadian misalignment" which can result in adverse health outcomes, including overeating, impaired glucose tolerance, insulin sensitivity, and cardiovascular disease risk. This study will provide proof-of-concept evidence on the impact of misalignment on glucose metabolism and blood pressure regulation. This study will focus on overweight individuals who are at high risk of obesity but are still on a trajectory that can potentially be reversed by lifestyle changes. Following a careful assessment of the subject's habitual sleep and meal timing and caloric distribution under real life conditions, a short laboratory study will determine 24hr profiles of hormones involved in circadian timing, food intake and cardiovascular risk in a session that will mimic habitual sleep/wake and caloric distribution. Participants will then be randomized to one of three groups in which caloric distribution across the day will either be equally distributed between 3 meals, or heavily weighted to the morning or heavily weighted to the evening. During a 6-day semi-ambulatory in patient intervention, combining laboratory and ambulatory procedures, study procedures will assess the effect of experimentally changing caloric distribution across the day, advancing versus delaying the dietary chronotype. After 7 days of this caloric distribution intervention, we will then repeat the short laboratory session to assess whether the intervention of caloric distribution altered any of the measured profiles. The outcome measures will be the timing of the dim light melatonin onset (DLMO), blood pressure dipping, and insulin sensitivity. The proposed work will provide unambiguous evidence related to the efficacy of a novel lifestyle intervention - that could be more acceptable than dietary restriction or exercise - to reduce the risk of T2DM and CVD in adults at risk due to age and degree of adiposity. Moreover, our project will examine both middle-aged adults and older adults. The younger age group is of interest because of a lesser burden of illness and of an opportunity to alter the trajectory of aging at an earlier stage. The older age group is expected to have more severe circadian disturbances at baseline, with the potential of a larger effect on CM risk. The combined examination of metabolic risk and CVD risk in the context of circadian function is also novel.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: January 1, 2027
• Est. primary completion date: March 13, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

• Healthy overweight and obese (25 kg/m2 =BMI< 40 kg/m2) men and women

• aged 30-75 years

• self-report sleeping at least 6.5-hrs/night but no more than 9-hrs/night, between 21:00 and 09:00

• signed informed consent

Exclusion Criteria:

• participation in a medically managed weight loss program within the past year

• undergone bariatric surgery

• dietary restrictions

• Subjects will not have undergone surgery, donated a unit of blood, worked night shifts or crossed any time zones, or participated in another clinical study within a month prior to the study.

• pregnancy in women

• lactating women

• Female subjects must not be actively going through menopause.

• prisoners

• inability to consent

• members of the study team

• Females with a hemoglobin < 11.5g/dL, and males with a hemoglobin < 13.5 g/dl will be excluded from the study.

• presence of a sleep disorder such as moderate or severe sleep apnea (AHI=15), a Circadian Rhythm Sleep Disorder (DSM-V criteria for advance sleep phase syndrome, delayed sleep phase syndrome, non 24-h sleep disorder, irregular sleep disorder and shift-work related sleep disorder),

• a diagnosis of diabetes based on history or screening tests

• other forms of endocrine dysfunction including PCOS;

• a history of cognitive or other neurological disorders;

• a history of major psychiatric disorder based on DSM-V criteria,

• the presence of unstable or serious medical conditions,

• any GI disease that requires dietary adjustment;

• current, or use within the past month of melatonin, psychoactive, hypnotic, stimulant or pain medications (except occasionally); beta blockers; habitual smoking (6 or more cigarettes per week); caffeine consumption of greater than 500 mg per day

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Intervention

Behavioral:
• Early Total Caloric Intake
Provide subjects a regimented amount of calories at each meal.
• Late Total Caloric Intake
Provide subjects a regimented amount of calories at each meal.
• Extended Overnight Fast
Provide subjects a regimented amount of calories at each meal.

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
University of Chicago	National Institute on Aging (NIA), Northwestern University

Country where clinical trial is conducted

United States, 

References & Publications (17)

Arble DM, Bass J, Behn CD, Butler MP, Challet E, Czeisler C, Depner CM, Elmquist J, Franken P, Grandner MA, Hanlon EC, Keene AC, Joyner MJ, Karatsoreos I, Kern PA, Klein S, Morris CJ, Pack AI, Panda S, Ptacek LJ, Punjabi NM, Sassone-Corsi P, Scheer FA, Sa — View Citation

Arble DM, Ramsey KM, Bass J, Turek FW. Circadian disruption and metabolic disease: findings from animal models. Best Pract Res Clin Endocrinol Metab. 2010 Oct;24(5):785-800. doi: 10.1016/j.beem.2010.08.003. — View Citation

Buxton OM, Cain SW, O'Connor SP, Porter JH, Duffy JF, Wang W, Czeisler CA, Shea SA. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med. 2012 Apr 11;4(129):129ra43. doi: 10.1126/scitra — View Citation

Dibner C, Schibler U. Circadian timing of metabolism in animal models and humans. J Intern Med. 2015 May;277(5):513-27. doi: 10.1111/joim.12347. Epub 2015 Feb 6. — View Citation

Gerhart-Hines Z, Lazar MA. Circadian metabolism in the light of evolution. Endocr Rev. 2015 Jun;36(3):289-304. doi: 10.1210/er.2015-1007. Epub 2015 Apr 30. — View Citation

Gill S, Panda S. A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans that Can Be Modulated for Health Benefits. Cell Metab. 2015 Nov 3;22(5):789-98. doi: 10.1016/j.cmet.2015.09.005. Epub 2015 Sep 24. — View Citation

Grimaldi D, Carter JR, Van Cauter E, Leproult R. Adverse Impact of Sleep Restriction and Circadian Misalignment on Autonomic Function in Healthy Young Adults. Hypertension. 2016 Jul;68(1):243-50. doi: 10.1161/HYPERTENSIONAHA.115.06847. Epub 2016 Jun 6. — View Citation

Leproult R, Holmback U, Van Cauter E. Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss. Diabetes. 2014 Jun;63(6):1860-9. doi: 10.2337/db13-1546. Epub 2014 Jan 23. — View Citation

Maury E, Hong HK, Bass J. Circadian disruption in the pathogenesis of metabolic syndrome. Diabetes Metab. 2014 Nov;40(5):338-46. doi: 10.1016/j.diabet.2013.12.005. Epub 2014 Jan 14. — View Citation

McHill AW, Melanson EL, Higgins J, Connick E, Moehlman TM, Stothard ER, Wright KP Jr. Impact of circadian misalignment on energy metabolism during simulated nightshift work. Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):17302-7. doi: 10.1073/pnas.141202111 — View Citation

Morris CJ, Garcia JI, Myers S, Yang JN, Trienekens N, Scheer FA. The Human Circadian System Has a Dominating Role in Causing the Morning/Evening Difference in Diet-Induced Thermogenesis. Obesity (Silver Spring). 2015 Oct;23(10):2053-8. doi: 10.1002/oby.21 — View Citation

Morris CJ, Purvis TE, Mistretta J, Scheer FA. Effects of the Internal Circadian System and Circadian Misalignment on Glucose Tolerance in Chronic Shift Workers. J Clin Endocrinol Metab. 2016 Mar;101(3):1066-74. doi: 10.1210/jc.2015-3924. Epub 2016 Jan 15. — View Citation

Morris CJ, Yang JN, Garcia JI, Myers S, Bozzi I, Wang W, Buxton OM, Shea SA, Scheer FA. Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans. Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2225- — View Citation

Peek CB, Ramsey KM, Marcheva B, Bass J. Nutrient sensing and the circadian clock. Trends Endocrinol Metab. 2012 Jul;23(7):312-8. doi: 10.1016/j.tem.2012.02.003. Epub 2012 Mar 16. — View Citation

Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4453-8. doi: 10.1073/pnas.0808180106. Epub 2009 Mar 2. — View Citation

Summa KC, Turek FW. Chronobiology and obesity: Interactions between circadian rhythms and energy regulation. Adv Nutr. 2014 May 14;5(3):312S-9S. doi: 10.3945/an.113.005132. Print 2014 May. — View Citation

Zarrinpar A, Chaix A, Panda S. Daily Eating Patterns and Their Impact on Health and Disease. Trends Endocrinol Metab. 2016 Feb;27(2):69-83. doi: 10.1016/j.tem.2015.11.007. Epub 2015 Dec 17. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MI-IS	The primary outcome measure is the Matsuda Index of Insulin Sensitivity.	15 days