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High Resolution Phenotyping in Healthy Humans

This study has been completed.
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00943774
First received: July 20, 2009
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

Baroreflex sensitivity is integral to blood pressure regulation, and varies among healthy, normotensive individuals. A reduced compensatory ability of baroreflex buffering in patients with carotid denervation results in blood pressure variability and an elevated blood pressure response to mental stress. Furthermore, 24-hour ambulatory blood pressure variability may also be a significant and independent risk determinant of cardiovascular disease. It remains unknown whether the degree of baroreflex sensitivity and ambulatory blood pressure variability are predictive of the pressor response to sympathoexcitatory stress in healthy humans. In this study the investigators propose a comprehensive evaluation of the relationships among the pressor and forearm vasodilator response to sympathoexcitation, ambulatory blood pressure variability, and baroreflex sensitivity in healthy normotensive subjects. Ultimately this study will provide preliminary data and protocol development for large-scale high resolution phenotyping in population-based trials aimed at determining the functional relevance of candidate gene variation in intermediate physiological traits pertinent to the pathogenesis of hypertension and cardiovascular disease.


Condition Intervention
Pressor Response
Baroreflex Sensitivity
Blood Pressure Variability
Heart Rate Variability
Arterial Catecholamines
Other: Physiological maneuvers

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Blood Pressure Variability, Baroreflex Sensitivity, and Cardiovascular Responses to Sympathoexcitation in Healthy Normotensive Humans

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Blood Pressure Response to Sympathoexcitation [ Time Frame: On day of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Baroreflex Sensitivity [ Time Frame: On day of study ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

serum, white cells


Enrollment: 300
Study Start Date: April 2006
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
All subjects
All subject participants
Other: Physiological maneuvers
These healthy subjects undergo physiological testing, which includes aortic augmentation index, pulse wave velocity, orthostatic stress, baroreflex sensitivity (modified Oxford protocol), mental stress, cold pressor test, isometric handgrip, heart rate variability, 24-hour ambulatory blood pressure monitoring.

Detailed Description:

Growing evidence suggests an association of environmental stress with the development of hypertension and there is strong evidence in normotensive subjects that a greater pressor response to sympathoexcitatory stress is a harbinger of future hypertension. Pharmacological studies have shown that individuals with HTN have a blunted baroreflex sensitivity, and display a greater increase in blood pressure during administration of an alpha-agonist. Furthermore, exaggerated 24-hour ambulatory blood pressure variability (BPV) is proposed to be a risk factor for the development of cardiovascular disease. Finally, Beta-2 adrenergic receptor-mediated forearm vasodilator responses to mental stress are blunted in Caucasian subjects at increased risk for hypertension, in African Americans, and in mild hypertension. We postulate that a relationship exists between these variables, even in normotensive healthy individuals. We also believe that signs of subclinical metabolic dysfunction exist in healthy individuals and that they may either contribute to or be affected by BPV. There is also evidence the prematurity at birth and low birth weight are associated with hypertension. Finally, arterial stiffness may also be related to blood pressure variability and the pressor response. Therefore the specific aims of this study are:

  1. To examine the relationship between 24-hour ambulatory BPV and baroreflex sensitivity. By measuring the baroreflex control of heart rate during sequential boluses of nitroprusside and phenylephrine, we hypothesize that baroreflex sensitivity will be inversely related to the degree of 24-hour BPV.
  2. To examine the relationship between 24-hour ambulatory BPV and the pressor response to four sympathoexcitatory maneuvers: head-up tilt testing, mental stress, cold pressor test, and isometric handgrip to fatigue. We hypothesize that greater BPV will predict the pressor response to stress.
  3. To examine the relationship between baroreflex sensitivity and the pressor response/forearm vasodilator response to the three sympathoexcitatory maneuvers. We hypothesize that individuals with higher baroreflex sensitivity will have a lower pressor response and a lower forearm vasodilator response to sympathoexcitatory stress.
  4. To draw a venous blood sample for future screening of genetic polymorphisms of interest, which may include nitric oxide synthase (NOS), alpha-adrenergic and beta-adrenergic receptor polymorphisms. We hypothesize that genetic variation in these key regulatory systems might explain some of the differences in baroreflex sensitivity, BPV, the pressor response and forearm vasodilator response to sympathoexcitation.
  5. To examine the relationship between 24-hour ambulatory BPV and the pressor response to sympathoexcitatory maneuvers and insulin resistance, dyslipidemia, and body fat distribution. We hypothesize that greater BPV will be associated with insulin resistance, dyslipidemia, and increase waist-hip ratio.
  6. To examine the relationship between 24-hour ambulatory BPV and arterial stiffness using measurements of pulse wave velocity. We hypothesize that greater BPV will be associated with increased pulse wave velocity, an index of arterial stiffness.
  7. To examine the relationship between 24-hour ambulatory BPV and the pressor response to sympathoexcitatory maneuvers with birth weight and post-conceptual age at birth. We will ask each subject to provide this data based on their birth certificate and/or knowledge of their medical history.
  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Residents of Southeast Minnesota

Criteria

Inclusion Criteria:

  • Men age 18-40
  • Non-pregnant women age 18-50

Exclusion Criteria:

  • Any medical conditions affecting the cardiovascular system
  • Any prescribed chronic medications (except contraceptives)
  • Extremes of fitness (not totally sedentary, not highly exercise-trained)
  • BMI greater than 28
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943774

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: John H. Eisenach, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00943774     History of Changes
Other Study ID Numbers: 05-004352, R01 HL-089331, NS-32352
Study First Received: July 20, 2009
Last Updated: February 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Physiology
Phenotype
Genetics
Genomics
Stress
Baroreflex
Blood Pressure
Arterial stiffness

ClinicalTrials.gov processed this record on November 27, 2014