Body Weight, Sleep, and Heart Health
Primary Purpose
Cardiovascular Risk Factor, Circadian Dysregulation, Obesity
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
PET Imaging
Circadian Study Protocol
11C-Meta-Hydroxyephedrine (mHED)
11C-CGP12177
O15-water
Sponsored by
About this trial
This is an interventional basic science trial for Cardiovascular Risk Factor
Eligibility Criteria
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)
Sites / Locations
- Oregon Health & Science University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Normal Weight
Overweight
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
Blood Pressure
Beat-by-beat and ambulatory blood pressure measurements.
Secondary Outcome Measures
Heart Rate
Heart rate via 2-channel echocardiogram (ECG)
Epinephrine
Venous Epinephrine to estimate sympathetic output
Norepinephrine
Venous Norepinephrine to estimate sympathetic output
Cortisol
Saliva cortisol to estimate sympathetic output
Aldosterone
Venous Aldosterone to estimate sympathetic output
Endocannabinoid
Plasma endocannabinoid to estimate sympathetic regulation
Heart Rate Variability (HRV)
Analysis of HRV from 12-lead ECG to assess parasympathetic activity
malondialdehyde (MDA) adducts
Plasma MDA to measure oxidative stress and inflammation.
Flow Mediated Dilation (FMD)
FMD to measure endothelial function.
Tumor Necrosis Factor alpha (TNF-alpha)
TNF-alpha to assess inflammation.
Coronary blood flow
Radiolabeled water (O15-water) to measure coronary blood flow during PET Imaging.
Norepinephrine reuptake transport
Radiolabeled meta-hydroxyephedrine (11C-mHED) to measure norepinephrine reuptake during PET Imaging.
Beta-adrenergic receptor density
Radiolabeled agonist (11C-CGP12177) to measure beta-adrenergic receptors during PET Imaging.
Dual Emission X-ray Absorbance (DEXA) Body composition
DEXA imaging to assess body composition.
Coronary Artery Calcium Score
Coronary Calcium Computed Tomography (CT) Scan
Coronary Microvascular Blood Flux
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.
Full Information
NCT ID
NCT03388788
First Posted
December 20, 2017
Last Updated
May 18, 2023
Sponsor
Oregon Health and Science University
1. Study Identification
Unique Protocol Identification Number
NCT03388788
Brief Title
Body Weight, Sleep, and Heart Health
Official Title
Circadian Mechanisms of Cardiovascular Risk in Obesity
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
March 15, 2023 (Actual)
Study Completion Date
March 15, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oregon Health and Science University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Risk Factor, Circadian Dysregulation, Obesity
7. Study Design
Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Normal Weight
Arm Type
Experimental
Arm Description
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).
Arm Title
Overweight
Arm Type
Experimental
Arm Description
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).
Intervention Type
Radiation
Intervention Name(s)
PET Imaging
Intervention Description
Positron Emission Tomography (PET) imaging for research.
Intervention Type
Behavioral
Intervention Name(s)
Circadian Study Protocol
Intervention Description
5-day circadian study schedule
Intervention Type
Drug
Intervention Name(s)
11C-Meta-Hydroxyephedrine (mHED)
Other Intervention Name(s)
11C-mHED
Intervention Description
11C-meta-hydroxyephedrine will be used during PET imaging to measure cardiac presynaptic norepinephrine transporter function.
Intervention Type
Drug
Intervention Name(s)
11C-CGP12177
Intervention Description
Cardiac beta adrenergic receptor density will be measured via PET imaging with infusion of 11C-CGP12177.
Intervention Type
Drug
Intervention Name(s)
O15-water
Intervention Description
Blood flow will be measured via PET imaging with infusion of O15-water.
Primary Outcome Measure Information:
Title
Blood Pressure
Description
Beat-by-beat and ambulatory blood pressure measurements.
Time Frame
5 Days
Secondary Outcome Measure Information:
Title
Heart Rate
Description
Heart rate via 2-channel echocardiogram (ECG)
Time Frame
5 Days
Title
Epinephrine
Description
Venous Epinephrine to estimate sympathetic output
Time Frame
5 days
Title
Norepinephrine
Description
Venous Norepinephrine to estimate sympathetic output
Time Frame
5 days
Title
Cortisol
Description
Saliva cortisol to estimate sympathetic output
Time Frame
5 days
Title
Aldosterone
Description
Venous Aldosterone to estimate sympathetic output
Time Frame
5 days
Title
Endocannabinoid
Description
Plasma endocannabinoid to estimate sympathetic regulation
Time Frame
5 days
Title
Heart Rate Variability (HRV)
Description
Analysis of HRV from 12-lead ECG to assess parasympathetic activity
Time Frame
5 days
Title
malondialdehyde (MDA) adducts
Description
Plasma MDA to measure oxidative stress and inflammation.
Time Frame
5 days
Title
Flow Mediated Dilation (FMD)
Description
FMD to measure endothelial function.
Time Frame
5 days
Title
Tumor Necrosis Factor alpha (TNF-alpha)
Description
TNF-alpha to assess inflammation.
Time Frame
5 days
Title
Coronary blood flow
Description
Radiolabeled water (O15-water) to measure coronary blood flow during PET Imaging.
Time Frame
5 days.
Title
Norepinephrine reuptake transport
Description
Radiolabeled meta-hydroxyephedrine (11C-mHED) to measure norepinephrine reuptake during PET Imaging.
Time Frame
5 days.
Title
Beta-adrenergic receptor density
Description
Radiolabeled agonist (11C-CGP12177) to measure beta-adrenergic receptors during PET Imaging.
Time Frame
5 days.
Title
Dual Emission X-ray Absorbance (DEXA) Body composition
Description
DEXA imaging to assess body composition.
Time Frame
1 day
Title
Coronary Artery Calcium Score
Description
Coronary Calcium Computed Tomography (CT) Scan
Time Frame
1 scan.
Title
Coronary Microvascular Blood Flux
Description
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.
Time Frame
3 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven A Shea, PhD
Organizational Affiliation
Oregon Institute of Occupational Health Sciences
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jeanne M Link, PhD
Organizational Affiliation
OHSU Center for Radiochemistry Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Body Weight, Sleep, and Heart Health
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