Influence of NEP Inhibition on Vascular Leak and Inflammation (NEPi-INFLAMMATION)
Status:
Not yet recruiting
Trial end date:
2024-03-15
Target enrollment:
Participant gender:
Summary
Acute Respiratory Distress Syndrome is a severe type of lung injury that affects 10% of
patients admitted to Intensive Care Units worldwide, with an unacceptably high mortality of
up to 48% in those with the most severe form of the condition. It is a complex and poorly
understood syndrome that results in progressive failure of the lungs. Crucially, the inflamed
lungs allow fluid to leak from the circulation into the airspace, so that patients' lungs
fill with fluid - "drowning from the inside". As this condition progresses, the patient
typically requires increasing amounts of oxygen and eventually, support from a ventilator. To
date, there are no effective treatments for ARDS that can limit, stop or repair this process.
This research study is aiming to look at a naturally occurring substance produced by blood
vessels, C-type natriuretic peptide (CNP). The investigators have evidence suggesting that
CNP plays a role in maintaining the barrier provided by blood vessels that stops fluid
leaking out into tissues. This is based on various studies done on CNP by the investigators
research group that have established its widespread role in maintaining cells that line blood
vessels and play a vital role in lungs' barrier function: the endothelium.
CNP is broken down in part by an enzyme called Neutral endopeptidase and therefore, drugs
that inhibit this enzyme would result in increased CNP concentration and activity. If CNP
does in fact strengthen the lungs' endothelial barrier, then this class of drug may benefit
patients with ARDS. The aim of this experimental medicine study is to assess the effect of
using the licensed NEP inhibitor Racecadotril, in a well-established, safe model of
inflammation-induced skin blisters in healthy human volunteers to determine primarily whether
the fluid accumulation i.e. leak, in these blisters is reduced by treatment with this drug.