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Trials
Published in: Trials 1/2016

Open Access 01-12-2016 | Study protocol

Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANCA-associated vasculitis (CANVAS): study protocol for a randomised controlled trial

Authors: Dimitrios Chanouzas, Lovesh Dyall, Peter Nightingale, Charles Ferro, Paul Moss, Matthew David Morgan, Lorraine Harper

Published in: Trials | Issue 1/2016

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Abstract

Background

The ANCA-associated vasculitides (AAV) are systemic autoimmune inflammatory disorders characterised by necrotising inflammation affecting small to medium-sized blood vessels. Despite improvements in survival, infection and cardiovascular disease remain leading causes of morbidity and mortality.
Considerable evidence suggests that CD4 + CD28null T-cell expansions, predominantly seen in Cytomegalovirus (CMV) seropositive individuals, are associated with systemic dysregulation of immune function leading to a heightened risk of infection and cardiovascular disease. In patients with AAV, CD4 + CD28null expansions are driven by CMV and are associated with an increased risk of infection and mortality.
The aim of this study is to explore in detail the ways in which CMV modulates the immune system and to determine whether treatment with valaciclovir blocks subclinical CMV reactivation in CMV seropositive AAV patients and ameliorates the CMV-induced adverse effects on the immune system.

Methods/design

CANVAS is a single-centre prospective open-label randomised controlled proof-of-concept trial of 50 adult CMV seropositive patients with stable AAV. Participants will be randomly allocated to receive valaciclovir orally (2 g QDS or reduced according to renal function) or no additional treatment for 6 months with an additional 6-month follow-up period. The primary outcome is the proportion of patients with CMV reactivation, as assessed by measurable viral load on quantitative blood and urine CMV polymerase chain reaction. The secondary outcomes are safety, change in the proportion of CD4+ CMV-specific T-cell population (defined as CD4 + CD28null cells) and change in soluble markers of inflammation from baseline to 6 months. Further tertiary and exploratory outcomes include persistence of the effect of valaciclovir on the proportion of CD4 + CD28null cells at 6 months post completion of treatment, change in the immune phenotype of CD4+ T cells and change in blood pressure and arterial stiffness parameters from baseline to 6 months.

Discussion

The results of this study will enable larger studies to be conducted to determine whether by controlling subclinical CMV reactivation, we can improve clinical endpoints such as infection and cardiovascular disease. The potential impact of this study is not limited to AAV, as CD4 + CD28null cells have been linked to adverse outcomes in other inflammatory conditions and in the context of an ageing immune system.

Trial registration

ClinicalTrials.gov Identifier NCT01633476 (registered 29 June 2012).
Appendix
Available only for authorised users
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Metadata
Title
Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANCA-associated vasculitis (CANVAS): study protocol for a randomised controlled trial
Authors
Dimitrios Chanouzas
Lovesh Dyall
Peter Nightingale
Charles Ferro
Paul Moss
Matthew David Morgan
Lorraine Harper
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1482-2

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