Implications of Circadian Variation of Human Endocannabinoid Levels on Obesity Risk

The purpose of this study is to examine how the timing of eating changes 24hr profiles of lipids involved in eating for pleasure and how the body makes and uses energy (metabolism).

Study Overview

• Status: Withdrawn
• Conditions: Obesity
• Intervention / Treatment: Behavioral: Early Total Caloric Intake; Behavioral: Late Total Caloric Intake

Detailed 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 and insulin sensitivity. Moreover, reward driven eating (eating for the pleasurable aspect instead of energy need) generally results in caloric intake well in excess of energy requirements and is recognized as a major culprit in the epidemic of obesity. The endocannabinoid (eCB) system is involved in both homeostatic processes (energy need only) that govern food intake, and has been shown to play a key role in reward eating. Thus, the role of circadian organization of the eCB system and how misalignment may contribute to overeating, overweight, obesity, and diabetes is the main focus of this study. The overall goal is to determine whether the timing of food intake is a major determinant of the 24 hour variation in eCB activity that in turn affects hunger and appetite, glucose metabolism, and insulin sensitivity. 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 whether participants who consume more of their daily calories later in the day (later dietary chronotype) display delays in the eCB rhythm and lower insulin sensitivity. During a 6-day 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. The outcome measures will be the timing of the daily peak of the eCB rhythm and insulin sensitivity. Identification of circadian misalignment of the eCB system as a mediator of increased food intake and reduced insulin sensitivity may help develop novel preventive strategies.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• self-report sleeping between 7-hrs/night and 9-hrs/night, between 22:00 and 08:00
• no previously diagnosed sleep disorders (including obstructive sleep apnea (OSA))
• no existing diagnosis of prediabetes or diabetes
• no history of endocrine dysfunction
• no history of psychiatric, cardiovascular, or eating disorders
• must not have a gastro-intestinal disease that requires dietary adjustment
• currently taking no medications (including birth control)

Exclusion Criteria:

• drug and nicotine use, habitual alcohol use of more than 2 drinks per day, and caffeine intake of more than 300 mg per day
• anyone who has participated in medically managed weight loss program within the past year
• anyone who has undergone bariatric surgery
• must not have dietary restrictions
• must not work night shifts or crossed any time zones in the month prior to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Total Caloric Intake; The Early Total Caloric Intake study group will consume the majority of their daily calories during breakfast.	Behavioral: Early Total Caloric Intake; Provide subjects a regimented amount of calories at each meal.
Active Comparator: Late Total Caloric Intake; The Late Total Caloric Intake study group will consume the majority of their daily calories during dinner.	Behavioral: Late Total Caloric Intake; Provide subjects a regimented amount of calories at each meal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the time of acrophase of the 24hr eCB profile	A shift in the timing ( time of day, h:mm) of the peak (acrophase) of the eCB rhythm.	Baseline to Day 38
Change in appetite/hunger and reward-related eating scores	The change in the temporal profile of hunger and appetite ratings (measured at 6 time points over a 24hr period) as well as reward-related eating (RRE) from baseline to after the intervention. The ratings of hunger and appetite, and RRE from baseline to intervention will be measured by number rating, on a 10 point scale for hunger and appetite and agree/don't agree or a 5-point scale for the RREs.	Baseline to Day 38
Change in glucose tolerance	The change in glucose tolerance from baseline to after the intervention will be measured. Glucose outcomes from CGM include Mean Absolute Glucose (MAG - mg/dl), Coefficient of Variation (CV - mg/dl), Standard Deviation (SD-mg/dl), Area Under the Curve (AUC - mg/dl), Time Spent in Range (TIR - minutes), Continuous Overall Net Glycemic Action (CONGA - (mg/dl) per minutes ).	Baseline to Day 38
Change in insulin sensitivity	The change in insulin sensitivity from baseline to after the intervention will be measured. Insulin sensitivity measurements from the MMT include area under the curve for insulin (pmol/L) and cpeptide (pmol/L) as well as peak values (pmol/L).	Baseline to Day 38

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weight	The change in weight (kilograms) from baseline after intervention will be measured.	Baseline to Day 38

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Erin Hanlon, PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: December 12, 2016
• First Submitted That Met QC Criteria: December 19, 2016
• First Posted (Estimated): December 22, 2016

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity
• Other Study ID Numbers: IRB16-1174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is currently no plan to make IPD available to other researchers.

Drug and device information, study documents

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