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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2008 by University of Edinburgh.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Encysive Pharmaceuticals
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01100736
First received: March 30, 2010
Last updated: April 8, 2010
Last verified: February 2008

March 30, 2010
April 8, 2010
January 2009
September 2010   (final data collection date for primary outcome measure)
  • Plasma ET-1 after 7-day administration of bosentan, sitaxsentan and placebo [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01100736 on ClinicalTrials.gov Archive Site
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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

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.
Not Provided
Interventional
Phase 0
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
  • Pulmonary Arterial Hypertension
  • Vasodilation
  • Vasoconstriction
  • Drug: Bosentan
    Bosentan 125mg tablets, orally, twice daily for 7 days
    Other Name: Tracleer
  • Drug: Sitaxsentan
    Sitaxsentan 100mg tablets, orally, once daily for 7 days
    Other Name: Thelin
  • 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
  • Experimental: Bosentan
    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
    Interventions:
    • Drug: Bosentan
    • Biological: Endothelin-3
  • Experimental: Sitaxsentan
    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
    Interventions:
    • Drug: Sitaxsentan
    • Drug: Placebo
    • Biological: Endothelin-3
  • Placebo Comparator: Placebo
    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
    Interventions:
    • Drug: Placebo
    • Biological: Endothelin-3
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
10
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September 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01100736
2008/W/CRC/01, 08/S1102/1
Yes
Professor David Webb, University of Edinburgh
University of Edinburgh
Encysive Pharmaceuticals
Not Provided
University of Edinburgh
February 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP