Body Weight, Sleep, and Heart Health
- Conditions
- ObesityCircadian DysregulationCardiovascular Risk Factor
- Interventions
- Radiation: PET ImagingBehavioral: Circadian Study ProtocolDrug: 11C-Meta-Hydroxyephedrine (mHED)Drug: 11C-CGP12177Drug: O15-water
- Registration Number
- NCT03388788
- Lead Sponsor
- Oregon Health and Science University
- Brief Summary
A multidisciplinary investigation examining the circadian mechanisms regulating cardiovascular (CV) risk in 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 in obesity. Furthermore, using an ingenious approach, the investigators propose to explore impairment in pre/post synaptic function in the cardiac left ventricle.
- Detailed Description
Overall, these studies will help us answer whether CV rhythms predispose obese individuals to increased CV disease risk - particularly around the vulnerable morning period. The results will serve as a foundation for clinical trials of appropriately timed dosing of medications targeting aspects of the CV system in obesity that increase effectiveness while decreasing side-effects.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
- Ages 25-65
- Lean and overweight (BMI 18.5-40kg/m2)
- Habitually sedentary
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Normal Weight PET Imaging Healthy lean controls \[18.5\<BMI\<25 kg/m2 and WC \<94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Normal Weight 11C-Meta-Hydroxyephedrine (mHED) Healthy lean controls \[18.5\<BMI\<25 kg/m2 and WC \<94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Overweight Circadian Study Protocol Healthy obese \[30≤BMI\<40 and waist circumference (WC) ≥94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Overweight O15-water Healthy obese \[30≤BMI\<40 and waist circumference (WC) ≥94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Normal Weight O15-water Healthy lean controls \[18.5\<BMI\<25 kg/m2 and WC \<94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Overweight 11C-Meta-Hydroxyephedrine (mHED) Healthy obese \[30≤BMI\<40 and waist circumference (WC) ≥94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Overweight PET Imaging Healthy obese \[30≤BMI\<40 and waist circumference (WC) ≥94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Normal Weight Circadian Study Protocol Healthy lean controls \[18.5\<BMI\<25 kg/m2 and WC \<94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Normal Weight 11C-CGP12177 Healthy lean controls \[18.5\<BMI\<25 kg/m2 and WC \<94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water). Overweight 11C-CGP12177 Healthy obese \[30≤BMI\<40 and waist circumference (WC) ≥94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water).
- Primary Outcome Measures
Name Time Method Blood Pressure 5 Days Beat-by-beat and ambulatory blood pressure measurements.
- Secondary Outcome Measures
Name Time Method Heart Rate 5 Days Heart rate via 2-channel echocardiogram (ECG)
Norepinephrine 5 days Venous Norepinephrine to estimate sympathetic output
Heart Rate Variability (HRV) 5 days Analysis of HRV from 12-lead ECG to assess parasympathetic activity
Aldosterone 5 days Venous Aldosterone to estimate sympathetic output
Norepinephrine reuptake transport 5 days. Radiolabeled meta-hydroxyephedrine (11C-mHED) to measure norepinephrine reuptake during PET Imaging.
Beta-adrenergic receptor density 5 days. Radiolabeled agonist (11C-CGP12177) to measure beta-adrenergic receptors during PET Imaging.
Dual Emission X-ray Absorbance (DEXA) Body composition 1 day DEXA imaging to assess body composition.
Coronary Artery Calcium Score 1 scan. Coronary Calcium Computed Tomography (CT) Scan
Tumor Necrosis Factor alpha (TNF-alpha) 5 days TNF-alpha to assess inflammation.
Coronary blood flow 5 days. Radiolabeled water (O15-water) to measure coronary blood flow during PET Imaging.
Epinephrine 5 days Venous Epinephrine to estimate sympathetic output
Cortisol 5 days Saliva cortisol to estimate sympathetic output
malondialdehyde (MDA) adducts 5 days Plasma MDA to measure oxidative stress and inflammation.
Flow Mediated Dilation (FMD) 5 days FMD to measure endothelial function.
Coronary Microvascular Blood Flux 3 days 1. Determine in lean healthy humans if coronary microvascular function, measured as coronary microvascular blood flux, has an endogenous circadian rhythm with lowest function in the morning. 2. Test the hypothesis that people with obesity have impaired coronary microvascular blood flux compared to lean individuals, with the exaggerated impairment during the morning. Measured using myocardial contrast echocardiography.
Endocannabinoid 5 days Plasma endocannabinoid to estimate sympathetic regulation
Trial Locations
- Locations (1)
Oregon Health & Science University
🇺🇸Portland, Oregon, United States