Endothelin Receptor Function and Acute Stress (End-Stress)

Augusta University

Status: Active, not recruiting

Conditions: Hypertension

Treatments: Drug: Bosentan; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02116335

End-Stress

5P01HL069999 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 320 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

320 participants in 2 patient groups, including a placebo group

Bosentan

Experimental group

Description:

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

Treatment:

Drug: Bosentan

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo