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Endothelin Receptor Function and Acute Stress (End-Stress)

Primary Purpose

Hypertension

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Bosentan
Placebo
Sponsored by
Augusta University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension focused on measuring arterial stiffness, flow-mediated dilation, endothelial function, pulse wave velocity, inflammation, oxidative stress, Nitric Oxide, Cold Pressor Test, physio flow, Bosentan, Endothelin Receptor, Endothelin-1, BMI, stress, blood pressure

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Men and premenopausal women (Ages 18-50 years old)
  • Self-reported Black and White adults
  • Lean adults (BMl <25 kg/m^)
  • Obese adults (BMl > 30 kg/m^)

Exclusion Criteria:

  • Having a BMI less than 16 kg/m2 (severely and very severely underweight) or that is greater than 40 kg/m2 (Class III obesity)
  • Having evidence of cardiovascular, pulmonary, renal, hepatic, cerebral, or metabolic disease
  • Having evidence of pregnancy
  • Using medications that affect vascular tone (i.e., nitrates, etc.)
  • Postmenopausal women
  • Uncontrolled hypertension
  • Individuals who are on a restricted salt diet
  • Having a history of chronic pain
  • Having a history of rheumatoid arthritis
  • Using medications that are contraindicated with bosentan (i.e. glyburide, cyclosporine)
  • Liver dysfunction (which may be identified with the blood sample we take)

Sites / Locations

  • Georgia Regents University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Bosentan

Placebo

Arm Description

Sub-Chronic (3 days) Bosentan 250mg/day.

Stress response and endothelial function will be determined following a three day treatment of placebo

Outcomes

Primary Outcome Measures

Flow-Mediated Dilation (FMD)
Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function.

Secondary Outcome Measures

Arterial Stiffness Evaluation (PWV)
A tonometer will be gently applied on the carotid artery and then the femoral artery and the radial artery to record how fast blood flows between each of the points.
Physio Flow
Six surface electrodes will be placed on the body. 2 on the neck, 2 on the chest, and 2 on the back in order to measure parameters of the heart during exercise.
Femoral blood flow
Though ultrasound assessment; resistance of the blood flow, blood flow, blood velocity, and arterial diameter will all be measured in the femoral artery during the physically induced stress test which involves submerging the subjects hand in ice water for 3 minutes.
Blood Pressure
Blood pressure will measured in response to the physically induced stress test which involves submerging the subjects hand in ice water for 3 minutes.
Resting Energy Expenditure
REE will be assessed before and following treatment

Full Information

First Posted
April 14, 2014
Last Updated
July 18, 2022
Sponsor
Augusta University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT02116335
Brief Title
Endothelin Receptor Function and Acute Stress
Acronym
End-Stress
Official Title
Endothelin Receptor Function and Acute Stress (End-Stress)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2015 (undefined)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Augusta University
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Our bodies respond differently to stress. Animal studies by the investigators have found that endothelin-1 plays a role in regulating blood pressure in response to stress. This study is an extension of the investigators previous animal work to evaluate the role of endothelin-1 during stress in humans.
Detailed Description
Using a salt sensitive animal model of prehypertension, the Dahl S rat,the investigators have previously published that acute stress elicits a pressor response that is accompanied by an increase in 8 isoprostane and endothelin-1. However, the pressor response is suppressed by endothelin A/B receptor antagonism. Moreover, the investigators have identified that the increase in 8-isoprostane occurs downstream of endothelin receptor activation. These data indicate that endothelin receptor activation is a main player In the pressor response to acute stress in pre-hypertensive animals; however, this phenomenon has yet to be elucidated in humans.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
arterial stiffness, flow-mediated dilation, endothelial function, pulse wave velocity, inflammation, oxidative stress, Nitric Oxide, Cold Pressor Test, physio flow, Bosentan, Endothelin Receptor, Endothelin-1, BMI, stress, blood pressure

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
320 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bosentan
Arm Type
Experimental
Arm Description
Sub-Chronic (3 days) Bosentan 250mg/day.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Stress response and endothelial function will be determined following a three day treatment of placebo
Intervention Type
Drug
Intervention Name(s)
Bosentan
Other Intervention Name(s)
Tracleer
Intervention Description
Stress response and vascular function will be assessed 3 days following 125 mg twice per day of Bosentan
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
lactose capsule
Intervention Description
Stress response and vascular function will be assessed 3 days following twice per day placebo
Primary Outcome Measure Information:
Title
Flow-Mediated Dilation (FMD)
Description
Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function.
Time Frame
Baseline and 3 days
Secondary Outcome Measure Information:
Title
Arterial Stiffness Evaluation (PWV)
Description
A tonometer will be gently applied on the carotid artery and then the femoral artery and the radial artery to record how fast blood flows between each of the points.
Time Frame
Baseline and 3 days
Title
Physio Flow
Description
Six surface electrodes will be placed on the body. 2 on the neck, 2 on the chest, and 2 on the back in order to measure parameters of the heart during exercise.
Time Frame
Baseline and 3 days
Title
Femoral blood flow
Description
Though ultrasound assessment; resistance of the blood flow, blood flow, blood velocity, and arterial diameter will all be measured in the femoral artery during the physically induced stress test which involves submerging the subjects hand in ice water for 3 minutes.
Time Frame
Baseline and 3 days
Title
Blood Pressure
Description
Blood pressure will measured in response to the physically induced stress test which involves submerging the subjects hand in ice water for 3 minutes.
Time Frame
Baseline and 3 days
Title
Resting Energy Expenditure
Description
REE will be assessed before and following treatment
Time Frame
Baseline and 3 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Men and premenopausal women (Ages 18-50 years old) Self-reported Black and White adults Lean adults (BMl <25 kg/m^) Obese adults (BMl > 30 kg/m^) Exclusion Criteria: Having a BMI less than 16 kg/m2 (severely and very severely underweight) or that is greater than 40 kg/m2 (Class III obesity) Having evidence of cardiovascular, pulmonary, renal, hepatic, cerebral, or metabolic disease Having evidence of pregnancy Using medications that affect vascular tone (i.e., nitrates, etc.) Postmenopausal women Uncontrolled hypertension Individuals who are on a restricted salt diet Having a history of chronic pain Having a history of rheumatoid arthritis Using medications that are contraindicated with bosentan (i.e. glyburide, cyclosporine) Liver dysfunction (which may be identified with the blood sample we take)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan Harris, Ph.D.
Organizational Affiliation
Augusta University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgia Regents University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
Links:
URL
http://www.livep.net
Description
Laboratory of Integrative Vascular and Exercise Physiology

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Endothelin Receptor Function and Acute Stress

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