Endothelin Antagonism in ANCA Vasculitis

Vasculitis Clinical Trial

Official title:

The Vascular Effects of Endothelin Receptor Antagonism in Systemic Vasculitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02062346
• Other study ID #: Bean ICRF clinical study
• Status: Completed
• Phase: N/A
• Start date: August 2016
• Est. completion date: January 1, 2020

Study information

• Verified date: November 2023
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with vasculitis commonly develop cardiovascular disease. The reasons for this are not clear and is not adequately treated with current drugs. It is thus understand the reasons why patients with vasculitis develop cardiovascular disease in order to develop new drugs to reduced this risk.

Endothelin is a chemical produced by blood vessels that contributes to the development of hypertension and cardiovascular disease Higher than normal levels of endothelin are seen in patients with vasculitis but how this contributes to cardiovascular disease in patients with vasculitis is not clear. By using drugs that block the effects of endothelin ('endothelin receptor antagonists') the investigators can hopefully reduce the risk of cardiovascular disease in patients with vasculitis. The purpose of the study is to ascertain if endothelin receptor antagonists improve blood vessel function in patients with vasculitis.

Description:

Vasculitis patients and healthy controls matched for age, sex will be enrolled into the study. Patients will attend for 4 study days >1 week apart, whereas controls will attend for single day. Circulating Mφ and other immune cells will be confirmed using FACS prior each study.

Study 1 Both patients and control will attend for visit 1: assessment of vascular function using forearm plethysmography as part of case control study.

Vasculitis patients will then attend for visits 2, 3 & 4 as part of randomised three way crossover study (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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: January 1, 2020
• Est. primary completion date: January 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Male or female

• Age 18 years and over

• Body mass index =35

• Normal serum albumin

Exclusion Criteria:

• Subject with diabetes or current smoking or chronic kidney disease (eGFR <60ml/min)

• Subject with pre-existing cardiovascular disease

• 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)

• 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)

Related Conditions & MeSH terms

• Vasculitis

Intervention

Drug:
• BQ123
Intravenous infusion of BQ123 ( selective ETA antagonist )
• BQ123/788
or BQ123/788 (mixed ETA/B antagonists)
• Placebo
Intravenous infusion of saline

Locations

Country	Name	City	State
United Kingdom	University of Edinburgh	Edinburgh	Midlothian
United Kingdom	University of Edinburgh	Edinburgh

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	British Heart Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study 1 - forearm blood flow	Response to endothelium-dependent vasodilators	20mins
Primary	Study 2 - pulse wave velocity	Response of participants to ET antagonism	4 hours
Secondary	Study 1 - tPA release	Response of fibrinolytic system to endothelial vasodilators	20min
Secondary	Study 1 - baseline pulse wave velocity	Baseline arterial stiffness	Baseline
Secondary	Study 2 - tPA release	Response of participants to ET antagonism	4 hours