Endothelin Antagonism in ANCA Vasculitis

NCT ID: NCT02062346

Last Updated: 2023-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-31

Study Completion Date

2020-01-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Vasculitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

Saline placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Intravenous infusion of saline

BQ123

Intravenous infusion of BQ123 1000nmol/min for 15min

Group Type EXPERIMENTAL

BQ123

Intervention Type DRUG

Intravenous infusion of BQ123 ( selective ETA antagonist )

BQ123/788

Intravenous infusion of BQ123 1000nmol/min and BQ788 300nmol/min

Group Type EXPERIMENTAL

BQ123/788

Intervention Type DRUG

or BQ123/788 (mixed ETA/B antagonists)

Assessment of forearm vascular function

Response of forearm blood flow to endothelium-dependent and endothelium-independent vasodilators

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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BQ123

Intravenous infusion of BQ123 ( selective ETA antagonist )

Intervention Type DRUG

BQ123/788

or BQ123/788 (mixed ETA/B antagonists)

Intervention Type DRUG

Placebo

Intravenous infusion of saline

Intervention Type DRUG

Other Intervention Names

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Selective ETA antagonism mixed ETA/B antagonism Saline

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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British Heart Foundation

OTHER

Sponsor Role collaborator

University of Edinburgh

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Neeraj Dhaun

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh

Locations

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University of Edinburgh

Edinburgh, Midlothian, United Kingdom

Site Status

University of Edinburgh

Edinburgh, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Farrah TE, Melville V, Czopek A, Fok H, Bruce L, Mills NL, Bailey MA, Webb DJ, Dear JW, Dhaun N. Arterial stiffness, endothelial dysfunction and impaired fibrinolysis are pathogenic mechanisms contributing to cardiovascular risk in ANCA-associated vasculitis. Kidney Int. 2022 Nov;102(5):1115-1126. doi: 10.1016/j.kint.2022.07.026. Epub 2022 Aug 20.

Reference Type DERIVED
PMID: 35998848 (View on PubMed)

Other Identifiers

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Bean ICRF clinical study

Identifier Type: -

Identifier Source: org_study_id