End-Stress: Endothelin Receptor Function and Acute Stress

Sponsor

Augusta University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02116335

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

320

Enrollment

Location

Arms

103

Duration (Months)

3.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Bosentan Drug: Placebo	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

320 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Endothelin Receptor Function and Acute Stress (End-Stress)

Study Start Date :

Jun 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bosentan Sub-Chronic (3 days) Bosentan 250mg/day.	Drug: Bosentan Stress response and vascular function will be assessed 3 days following 125 mg twice per day of Bosentan Other Names: Tracleer
Placebo Comparator: Placebo Stress response and endothelial function will be determined following a three day treatment of placebo	Drug: Placebo Stress response and vascular function will be assessed 3 days following twice per day placebo Other Names: lactose capsule

Arm

Intervention/Treatment

Experimental: Bosentan

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

Drug: Bosentan

Stress response and vascular function will be assessed 3 days following 125 mg twice per day of Bosentan

Other Names:

Tracleer

Placebo Comparator: Placebo

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

Drug: Placebo

Stress response and vascular function will be assessed 3 days following twice per day placebo

Other Names:

lactose capsule

Outcome Measures

Primary Outcome Measures

Flow-Mediated Dilation (FMD) [Baseline and 3 days]
Brachial artery FMD induced by reactive hyperemia will be used to assess vascular endothelial function.

Secondary Outcome Measures

Arterial Stiffness Evaluation (PWV) [Baseline and 3 days]
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 [Baseline and 3 days]
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 [Baseline and 3 days]
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 [Baseline and 3 days]
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 [Baseline and 3 days]
REE will be assessed before and following treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)