Influence of NEP Inhibition on Vascular Leak and Inflammation (NEPi-INFLAMMATION)

NCT ID: NCT05600062

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-24
• Study Completion Date: 2026-06-15

Brief Summary

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.

Conditions

Acute Respiratory Distress Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Placebo tablet to be taken three times a day for three days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule

Racecadotril

Racecadotril 100 milligrams (mg) three times a day for three days

Group Type: EXPERIMENTAL

Racecadotril 100 milligram (MG) Oral Capsule

Intervention Type: DRUG

Licensed NEP inhibitor

Interventions

Racecadotril 100 milligram (MG) Oral Capsule

Licensed NEP inhibitor

Intervention Type: DRUG

Placebo

Placebo capsule

Intervention Type: DRUG

Other Intervention Names

Tiorfan

Eligibility Criteria

Inclusion Criteria

1. Healthy male and female volunteers

2. BMI of 18-40 kg/m2

3. Aged 18-45

4. Volunteers who are willing to sign the consent form

Exclusion Criteria

1. Healthy subjects unwilling to consent

2. Smokers

3. Known sensitivity to Racecadotril

4. History of any serious illnesses, including recent infections or trauma

5. A personal history of keloid scarring, or a family history of keloid scarring in a first degree relative with similar skin pigmentation

6. Subjects taking systemic medication (other than the oral contraceptive pill)

7. Subjects who are pregnant or any possibility that a subject may be pregnant, unless in the latter case a pregnancy test is performed with a negative result

8. Women who are breastfeeding

9. Subjects with recent or current antibiotic use

10. Subjects with a history of skins conditions.

11. Subjects with a history of allergic reaction to any topical application or history of angioedema

12. Subjects with any history of a blood-borne infectious disease such Hepatitis B or C virus, or HIV.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

Queen Mary University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adrian Hobbs

Role: PRINCIPAL_INVESTIGATOR

Queen Mary University London

Locations

William Harvey Research Institute- Heart Centre

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Aemun Salam, MBBS, MRCP, FFICM

Role: CONTACT

aemun.salam@qmul.ac.uk

07492042830

Facility Contacts

Aemun Salam

Role: primary

aemun.salam@qmul.ac.uk

Other Identifiers

288749

Identifier Type: -

Identifier Source: org_study_id