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Endothelin Antagonism in ANCA Vasculitis

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ClinicalTrials.gov Identifier: NCT02062346
Recruitment Status : Recruiting
First Posted : February 13, 2014
Last Update Posted : March 20, 2019
Sponsor:
Collaborator:
British Heart Foundation
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:

Patients with vasculitis commonly develop high blood pressure (hypertension) and this is associated with an increased risk of heart disease. It is thus important to lower blood pressure in those with hypertension. However, hypertension in vasculitis is inadequately controlled with many currently available blood pressure lowering agents.

Endothelin is a chemical produced by blood vessels that contributes to the development of hypertension. Higher than normal levels of endothelin are seen in patients with vasculitis. By using drugs that block the effects of endothelin ('endothelin receptor antagonists') the investigators can hopefully treat hypertension in patients with vasculitis. The purpose of the study is to ascertain whether endothelin receptor antagonists lower blood pressure and improve blood vessel function more effectively in patients with vasculitis than those without it.


Condition or disease Intervention/treatment Phase
Vasculitis Drug: BQ123 Drug: BQ123/788 Drug: Placebo Not Applicable

Detailed Description:

Vasculitis patients - matched for age, BP and renal function - will be recruited into 3 groups defined by their induction immunosuppression: (i) Azathioiprine, (ii) Mycophenolate mofetil, (iii) Rituximab. A 4th group will comprise control healthy subjects (n=10 for each). Subjects will attend for 4 study days >1 week apart. Circulating Mφ and other immune cells will be confirmed using FACS prior to each study. Day 1: assessment of vascular function. Days 2, 3 & 4 (randomised & infusions given in a double-blind method): comparison of the effects of selective ETA receptor antagonism (BQ123; 1000nmol/min for 15min iv), mixed ETA/B antagonism (BQ123/788; 1000 nmol/min & 300 nmol/min for 15 min), and placebo on systemic haemodynamics.

Outcome measures

  • Forearm blood flow
  • tPA release
  • Blood pressure
  • Aix & PWV

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Vascular Effects of Endothelin Receptor Antagonism in Systemic Vasculitis
Study Start Date : August 2016
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vasculitis

Arm Intervention/treatment
Placebo Comparator: Placebo
Saline placebo
Drug: Placebo
Intravenous infusion of saline
Other Name: Saline

Experimental: BQ123
Intravenous infusion of BQ123 1000nmol/min for 15min
Drug: BQ123
Intravenous infusion of BQ123 ( selective ETA antagonist )
Other Name: Selective ETA antagonism

Experimental: BQ123/788
Intravenous infusion of BQ123 1000nmol/min and BQ788 300nmol/min
Drug: BQ123/788
or BQ123/788 (mixed ETA/B antagonists)
Other Name: mixed ETA/B antagonism

No Intervention: Assessment of forearm vascular function
Response of forearm blood flow to endothelium-dependent and endothelium-independent vasodilators



Primary Outcome Measures :
  1. Blood pressure [ Time Frame: 4h ]
    Response of participants to ET antagonism


Secondary Outcome Measures :
  1. Forearm blood flow [ Time Frame: 20min ]
    Response to endothlium dependent and endothelium independent vasodilators


Other Outcome Measures:
  1. tPA release [ Time Frame: 20min ]
    Response of fibrinolytic system to endothelial vasodilators

  2. Pulse wave velocity [ Time Frame: 4 hours ]
    Response of participants to ET antagonism



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female
  • Age 18-80
  • Body mass index ≤35
  • Normal serum albumin

Exclusion Criteria:

  • Subject is below the age of legal consent, or is mentally or legally incapacitated
  • History of multiple and/or severe allergic reactions to drugs (including study drugs), or food
  • The subject has donated blood (450 ml) within the last 4 weeks
  • Past or present drug or alcohol abuse including intravenous drug abuse at any time
  • Participation in another clinical trial within 1 month
  • Considered to be at high risk of HIV or hepatitis B
  • Women of child-bearing potential (only women who are post-menopausal or surgically-sterilised will be included in the study)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02062346


Contacts
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Contact: Neeraj Dhaun, MD bean.dhaun@ed.ac.uk

Locations
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United Kingdom
University of Edinburgh Recruiting
Edinburgh, Midlothian, United Kingdom, EH16 4TJ
University of Edinburgh Recruiting
Edinburgh, United Kingdom
Contact: Neeraj Dhaun         
Sponsors and Collaborators
University of Edinburgh
British Heart Foundation
Investigators
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Principal Investigator: Neeraj Dhaun University of Edinburgh

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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT02062346     History of Changes
Other Study ID Numbers: Bean ICRF clinical study
First Posted: February 13, 2014    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019
Keywords provided by University of Edinburgh:
endothelin;
blood pressure;
vasculitis
Additional relevant MeSH terms:
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Vasculitis
Vascular Diseases
Cardiovascular Diseases
cyclo(Trp-Asp-Pro-Val-Leu)
Antihypertensive Agents
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action