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| Name | Class |
|---|---|
| Medical Research Council | OTHER_GOV |
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Acute Respiratory Distress Syndrome (ARDS) 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo tablet to be taken three times a day for three days |
|
| Racecadotril | Experimental | Racecadotril 100 milligrams (mg) three times a day for three days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Racecadotril 100 milligram (MG) Oral Capsule | Drug | Licensed NEP inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Powered unpaired inter-patient comparison of change in blister fluid volume following Racecadotril or placebo administration. | 24 hours after application of cantharidin | |
| Powered paired intra-patient comparison of change in blister fluid volume following Racecadotril or placebo admininstration. | 24 hours after application of cantharidin |
| Measure | Description | Time Frame |
|---|---|---|
| Powered comparison of sex differences in change in blister volume following Racecadotril or placebo administration. | End of study | |
| Difference in concentration of blister fluid cytokines; specifically Interleukin (IL) -1β, IL-6, IL-8, IL-10, CXCL1, CXCL2, CCL5 and CCL2 in volunteers receiving Racecadotril compared to placebo. |
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Inclusion Criteria:
Exclusion Criteria:
Equal number of males and females
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| Name | Affiliation | Role |
|---|---|---|
| Adrian Hobbs | Queen Mary University London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| William Harvey Research Institute- Heart Centre | London | United Kingdom |
Fully anonymised data will be shared with fellow researchers via conference presentation and via publication of the results in scientific journals. Data will be shared between the research team directly undertaking the research
6 months after publication
Access requests can be made to the investigators by email
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| D055371 | Acute Lung Injury |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D055370 | Lung Injury |
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| Placebo | Drug | Placebo capsule |
|
| 24 hours after application of cantharidin |
| Comparison of change in blister fluid leukocyte count following Racecadotril or placebo administration | 24 hours after application of cantharidin |
| Comparison of change in pro and anti-inflammatory mediators from blister fluid following Racecadotril or placebo administration | 24 hours after application of cantharidin |
| Comparison of change in plasma cGMP following oral Racecadotril or placebo administration | 24 hours after application of cantharidin |