Endothelin Receptor Function and Acute Stress (End-Stress)

• ClinicalTrials.gov Identifier: NCT02116335
• Recruitment Status: Active, not recruiting
• First Posted: April 16, 2014
• Last Update Posted: July 10, 2020
• Sponsor: Augusta University
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Ryan Harris, Augusta University

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	Not Applicable

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 (Clinical Trial)
• Estimated 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: June 2015
• Estimated Primary Completion Date: September 2020
• Estimated Study Completion Date: September 2020

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 Name: 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 Name: lactose capsule

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Arterial Stiffness Evaluation (PWV) [ Time Frame: 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.
2. Physio Flow [ Time Frame: 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.
3. Femoral blood flow [ Time Frame: 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.
4. Blood Pressure [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Locations

United States, Georgia

Georgia Regents University

Augusta, Georgia, United States, 30912

Sponsors and Collaborators

Augusta University

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Ryan Harris, Ph.D.; Augusta University

More Information

Additional Information:

Laboratory of Integrative Vascular and Exercise Physiology 

• Responsible Party: Ryan Harris, Assistant Professor, Augusta University
• ClinicalTrials.gov Identifier: NCT02116335
• Other Study ID Numbers: End-Stress; 5P01HL069999 ( U.S. NIH Grant/Contract )
• First Posted: April 16, 2014
• Last Update Posted: July 10, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by Ryan Harris, Augusta University:

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

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Bosentan; Antihypertensive Agents; Endothelin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action