NCT01100736

Role of Endothelin-A (ETA) and Endothelin-B (ETB) Receptors in the Vasodilatory Response to Endothelin-3 (ET-3)

Characterisation of the Role of ETA and ETB Receptors in Regulating Plasma ET-1 and the Vasodilator Response to ET-3 in Man

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: University of Edinburgh · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Endothelin-1 (ET-1) has been linked to a number of conditions including pulmonary arterial hypertension (PAH). ET-1 acts via 2 receptors, ETA and ETB. The ET-1 receptor blockers bosentan and sitaxsentan have been shown to be beneficial in patients with PAH. Bosentan blocks both ETA and ETB receptors. Sitaxsentan selectively blocks ETA receptors. Theoretically, selective ETA blockade may be associated with greater vasodilation and clearance of ET-1 by leaving the ETB receptor unblocked. This has not been directly studied in humans. We aim to investigate the endothelial ETB-mediated vascular responses between bosentan and sitaxsentan by using a ETB selective agonist (ET-3). We hypothesise that at clinically relevant doses: * Bosentan will show evidence of ETB receptor blockade compared to sitaxsentan and placebo. * These effects will be confirmed by 2 functional markers of ETB receptor antagonism: plasma ET-1 (a very sensitive, but not necessarily clinically relevant marker), and the forearm vasodilator response to ET-3.

Conditions

• Pulmonary Arterial Hypertension
• Vasodilation
• Vasoconstriction

Interventions

Type	Name	Description
DRUG	Bosentan	Bosentan 125mg tablets, orally, twice daily for 7 days
DRUG	Sitaxsentan	Sitaxsentan 100mg tablets, orally, once daily for 7 days
DRUG	Placebo	Placebo tablets taken twice daily, orally, for 7 days (placebo arm) or once daily for 7 days (sitaxsentan arm)
BIOLOGICAL	Endothelin-3	5 minute local intra-arterial infusion of endothelin-3 at a rate of rate of 60 pmol/min, during forearm blood flow studies

Timeline

• Start date: 2009-01-01
• Primary completion: 2009-09-01
• Completion: 2010-01-01
• First posted: 2010-04-09
• Last updated: 2015-07-21

Locations

1 site across 1 country: United Kingdom