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

NCT01100736 · Status: COMPLETED · Phase: EARLY_PHASE1 · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2015-07-21

No results posted yet for this study

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

Interventions

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

Sponsors & Collaborators

  • Encysive Pharmaceuticals

    collaborator INDUSTRY

  • University of Edinburgh

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Model
CROSSOVER

Eligibility

Min Age
18 Years
Max Age
70 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2009-01-31
Primary Completion
2009-09-30
Completion
2010-01-31

Countries

  • United Kingdom

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01100736 on ClinicalTrials.gov