An Early Phase 1 interventional study of Bosentan and Sitaxsentan in Pulmonary Arterial Hypertension, Vasodilation and Vasoconstriction, sponsored by University of Edinburgh. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2015-07-21.
Sponsored by University of Edinburgh · Early Phase 1, Interventional, and Basic science
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:
761 studies on the registry are indexed under Pulmonary Arterial Hypertension; 142 are open to participants now.
This study's planned enrollment of 10 is below the median of 38 across 509 interventional studies indexed under Pulmonary Arterial Hypertension.
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Bosentan 125mg twice daily will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of bosentan therapy
Drug: Bosentan · Biological: Endothelin-3
Sitaxsentan 100mg once daily + placebo tablet will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of sitaxsentan therapy
Drug: Sitaxsentan · Drug: Placebo · Biological: Endothelin-3
Placebo tablet twice daily will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of placebo therapy
Drug: Placebo · Biological: Endothelin-3
Bosentan 125mg tablets, orally, twice daily for 7 days
Also known as: Tracleer
Sitaxsentan 100mg tablets, orally, once daily for 7 days
Also known as: Thelin
Placebo tablets taken twice daily, orally, for 7 days (placebo arm) or once daily for 7 days (sitaxsentan arm)
5 minute local intra-arterial infusion of endothelin-3 at a rate of rate of 60 pmol/min, during forearm blood flow studies
Plasma ET-1 after 7-day administration of bosentan, sitaxsentan and placebo
Time frame: 7 days
Responses to ET-3 (maximum vasodilation after ET-3 administration and area under the curve of vasodilation) after bosentan compared with the results from sitaxsentan and placebo.
Time frame: 60 mins
This study is completed, as verified in Jul 2015. You cannot join it, but the record below documents what was studied.
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Pulmonary Arterial Hypertension→
University of Edinburgh