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Completed

NCT Number: NCT01100736

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

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.

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Key information

Conditions

Pulmonary Arterial Hypertension Aneurysm Cardiovascular Diseases Hypertension, Pulmonary Lung Diseases Respiratory Tract Diseases Vascular Diseases Vasoconstriction Vasodilation

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Clinical Research Centre, Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy men and post-menopausal women
  • Age 18-70 years
  • BMI 18-35 kg/m2

Exclusion criteria

  • Are mentally or legally incapacitated
  • Have donated blood within the last 4 weeks
  • Have a history of past or present drug or alcohol abuse
  • Have participated in another clinical trial within 1 month
  • Are considered to be at a high risk of HIV or Hepatitis B
  • Are taking routine medicines
  • Are women taking hormone replacement therapy
  • Have significant medical or psychiatric illness

Treatment and study plan

Bosentan

Drug

Bosentan 125mg tablets, orally, twice daily for 7 days

Other names: Tracleer

Sitaxsentan

Drug

Sitaxsentan 100mg tablets, orally, once daily for 7 days

Other names: Thelin

Placebo

Drug

Placebo tablets taken twice daily, orally, for 7 days (placebo arm) or once daily for 7 days (sitaxsentan arm)

Endothelin-3

Biological

5 minute local intra-arterial infusion of endothelin-3 at a rate of rate of 60 pmol/min, during forearm blood flow studies

Primary outcomes

  1. Plasma ET-1 after 7-day administration of bosentan, sitaxsentan and placebo

    Time frame: 7 days

  2. 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

Sponsors and collaborators

Lead sponsor

University of Edinburgh

Other

Collaborators

  • Encysive Pharmaceuticals

Registry information

Official study title

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

Important dates

Study start
2009
Primary completion
2009
Study completion
2010
First posted
Apr 9, 2010
Registry last updated
Jul 21, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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