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Body Weight, Sleep, and Heart Health

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ClinicalTrials.gov Identifier: NCT03388788
Recruitment Status : Recruiting
First Posted : January 3, 2018
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Steven A. Shea, 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.

Condition or disease Intervention/treatment Phase
Cardiovascular Risk Factor Circadian Dysregulation Obesity Radiation: PET Imaging Behavioral: Circadian Study Protocol Drug: 11C-Meta-Hydroxyephedrine (mHED) Drug: 11C-CGP12177 Drug: O15-water Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Circadian Mechanisms of Cardiovascular Risk in Obesity
Actual Study Start Date : May 1, 2018
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : May 31, 2021

Arm Intervention/treatment
Experimental: Normal Weight
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).
Radiation: PET Imaging
Positron Emission Tomography (PET) imaging for research.

Behavioral: Circadian Study Protocol
5-day circadian study schedule

Drug: 11C-Meta-Hydroxyephedrine (mHED)
11C-meta-hydroxyephedrine will be used during PET imaging to measure cardiac presynaptic norepinephrine transporter function.
Other Name: 11C-mHED

Drug: 11C-CGP12177
Cardiac beta adrenergic receptor density will be measured via PET imaging with infusion of 11C-CGP12177.

Drug: O15-water
Blood flow will be measured via PET imaging with infusion of O15-water.

Experimental: Overweight
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).
Radiation: PET Imaging
Positron Emission Tomography (PET) imaging for research.

Behavioral: Circadian Study Protocol
5-day circadian study schedule

Drug: 11C-Meta-Hydroxyephedrine (mHED)
11C-meta-hydroxyephedrine will be used during PET imaging to measure cardiac presynaptic norepinephrine transporter function.
Other Name: 11C-mHED

Drug: 11C-CGP12177
Cardiac beta adrenergic receptor density will be measured via PET imaging with infusion of 11C-CGP12177.

Drug: O15-water
Blood flow will be measured via PET imaging with infusion of O15-water.




Primary Outcome Measures :
  1. Blood Pressure [ Time Frame: 5 Days ]
    Beat-by-beat and ambulatory blood pressure measurements.


Secondary Outcome Measures :
  1. Heart Rate [ Time Frame: 5 Days ]
    Heart rate via 2-channel echocardiogram (ECG)

  2. Epinephrine [ Time Frame: 5 days ]
    Venous Epinephrine to estimate sympathetic output

  3. Norepinephrine [ Time Frame: 5 days ]
    Venous Norepinephrine to estimate sympathetic output

  4. Cortisol [ Time Frame: 5 days ]
    Saliva cortisol to estimate sympathetic output

  5. Aldosterone [ Time Frame: 5 days ]
    Venous Aldosterone to estimate sympathetic output

  6. Endocannabinoid [ Time Frame: 5 days ]
    Plasma endocannabinoid to estimate sympathetic regulation

  7. Heart Rate Variability (HRV) [ Time Frame: 5 days ]
    Analysis of HRV from 12-lead ECG to assess parasympathetic activity

  8. malondialdehyde (MDA) adducts [ Time Frame: 5 days ]
    Plasma MDA to measure oxidative stress and inflammation.

  9. Flow Mediated Dilation (FMD) [ Time Frame: 5 days ]
    FMD to measure endothelial function.

  10. Tumor Necrosis Factor alpha (TNF-alpha) [ Time Frame: 5 days ]
    TNF-alpha to assess inflammation.

  11. Coronary blood flow [ Time Frame: 5 days. ]
    Radiolabeled water (O15-water) to measure coronary blood flow during PET Imaging.

  12. Norepinephrine reuptake transport [ Time Frame: 5 days. ]
    Radiolabeled meta-hydroxyephedrine (11C-mHED) to measure norepinephrine reuptake during PET Imaging.

  13. Beta-adrenergic receptor density [ Time Frame: 5 days. ]
    Radiolabeled agonist (11C-CGP12177) to measure beta-adrenergic receptors during PET Imaging.

  14. Dual Emission X-ray Absorbance (DEXA) Body composition [ Time Frame: 1 day ]
    DEXA imaging to assess body composition.

  15. Coronary Artery Calcium Score [ Time Frame: 1 scan. ]
    Coronary Calcium Computed Tomography (CT) Scan

  16. Coronary Microvascular Blood Flux [ Time Frame: 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.



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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03388788


Contacts
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Contact: Andrew W McHill, PhD 5033463808 circadian@ohsu.edu
Contact: Daniel Chess, BS/BA 5854904146 circadian@ohsu.edu

Locations
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United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Andrew W McHill, PhD    503-494-2594    mchill@ohsu.edu   
Sponsors and Collaborators
Oregon Health and Science University
Investigators
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Principal Investigator: Steven A Shea, PhD Oregon Institute of Occupational Health Sciences
Principal Investigator: Jeanne M Link, PhD OHSU Center for Radiochemistry Research
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Responsible Party: Steven A. Shea, Director, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT03388788    
Other Study ID Numbers: IRB00017489
First Posted: January 3, 2018    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Chronobiology Disorders
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Nervous System Diseases
CGP 12177
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Antagonists
Adrenergic Antagonists