Body Weight, Sleep, and Heart Health

Circadian Mechanisms of Cardiovascular Risk in Obesity

A multidisciplinary investigation examining the circadian mechanisms regulating cardiovascular (CV) risk, with an additional focus on obesity. Specifically, in a valid circadian protocol, the investigators aim to study resting cardiovascular risk markers and the reactivity of circadian rhythms in these risk markers to standardized stressors. It is intended to compare results in lean and obese individuals to determine if there are specific risks across the circadian cycle specific to obesity. Furthermore, using an exploratory approach, the investigators propose to explore impairment in pre/post synaptic function in the cardiac left ventricle.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Cardiovascular Risk Factor; Circadian Dysregulation
• Intervention / Treatment: Combination product: Positron Emission Tomography (PET) scanning of cardiac function at 3 time points across the 24 hour circadian cycle

Detailed Description

Overall, these studies will help us answer whether the circadian system predispose individuals to increased CV disease risk - particularly around the vulnerable morning period, and whether these risks differ with obesity. The results will serve as a foundation for clinical trials of appropriately timed dosing of medications targeting aspects of the CV system that increase effectiveness while decreasing side effects, and may have particular relevance to management of CV risk in people with obesity.

• Study Type: Observational
• Enrollment (Actual): 17
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Community sample

Description

Inclusion Criteria:

• Ages 25-65
• Lean and overweight (BMI 18.5-40kg/m2)
• Habitually sedentary

Exclusion Criteria:

• History of smoking/tobacco use
• Insomnia
• Moderate to severe obstructive sleep apnea.
• Prior shift work within 6 months prior to the study.
• Prescription medications
• Drugs of abuse
• Acute, chronic, or debilitating medical condition (including diabetes, hypertension, and metabolic syndrome)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal Weight; Healthy lean controls [18.5<BMI<25 kg/m2 and waist circumference <94/80 cm (men/women respectively)] will participate in a 5-day circadian study protocol with numerous repeated cardiovascular measures across the circadian cycle. Drugs are used as part of physiological monitoring and not as interventions including imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, and 11C-CGP12177).	Combination product: Positron Emission Tomography (PET) scanning of cardiac function at 3 time points across the 24 hour circadian cycle; Drugs are used for as part of physiological monitoring and not as interventions, including imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, and 11C-CGP12177).; Other Names: PET scanning
Overweight; Healthy obese [30≤BMI<40 and waist circumference ≥94/80 (men and women respectively)] Healthy lean controls [18.5<BMI<25 kg/m2 and waist circumference <94/80 cm (men/women respectively)] will participate in a 5-day circadian study protocol with numerous repeated cardiovascular measures across the circadian cycle. Drugs are used as part of physiological monitoring and not as interventions including imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, and 11C-CGP12177).	Combination product: Positron Emission Tomography (PET) scanning of cardiac function at 3 time points across the 24 hour circadian cycle; Drugs are used for as part of physiological monitoring and not as interventions, including imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, and 11C-CGP12177).; Other Names: PET scanning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure (BP)	Measurements were collected up to 7 times per participant across the circadian cycle under constant conditions across 5 days. Resting BP and Exercise BP data were collected at the beginning of each of 7 wake periods in a supine position and where participants exercised at an intensity equivalent to brisk walking. Salivary melatonin was used to calculate the circadian phase marker using dim light melatonin onset (DLMO). All data were assigned a circadian phase relative to DLMO and binned into 4-hour (or 60-degree) intervals. In the statistical analysis, the weight group refers to normal or overweight, exercise condition refers to seated or exercising on the bike, and circadian phase refers to the center of the circadian bin. This is an observational study. Due to insufficient enrollment and an imbalanced group distribution, we do not have sufficient statistical power to fully interpret these data. The data are valuable as pilot data for future investigations and sample size estimation.	5 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Rate	Heart rate via 2-channel echocardiogram (ECG)	5 Days
Epinephrine	Venous Epinephrine to estimate sympathetic output	5 days
Norepinephrine	Venous Norepinephrine to estimate sympathetic output	5 days
Cortisol	Saliva cortisol to estimate sympathetic output	5 days
Flow Mediated Dilation (FMD)	FMD to measure endothelial function.	5 days
Coronary Microvascular Blood Flux	Coronary microvascular function, measured as coronary microvascular blood flux using myocardial contrast echocardiography.	3 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta-adrenergic Receptor Density (Exploratory Outcome)	Radiolabeled agonist (11C-CGP12177) to measure beta-adrenergic receptors during PET Imaging.	5 days.
Norepinephrine Reuptake Transport (Exploratory Outcome)	Radiolabeled meta-hydroxyephedrine (11C-mHED) to measure norepinephrine reuptake during PET Imaging.	5 days.

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Steven A Shea, PhD, Oregon Institute of Occupational Health Sciences; Principal Investigator: Jeanne M Link, PhD, OHSU Center for Radiochemistry Research

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): September 30, 2024
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: December 29, 2017
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Chronobiology Disorders; Investigative Techniques; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole
• Other Study ID Numbers: IRB00017489; KL2TR002370 (U.S. NIH Grant/Contract); R01HL140577 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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