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

Primary Purpose

Acute Respiratory Distress Syndrome

Status
Recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Racecadotril 100 milligram (MG) Oral Capsule
Placebo
Sponsored by
Queen Mary University of London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Acute Respiratory Distress Syndrome focused on measuring ARDS, endothelium, CNP, Acute lung injury

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Healthy male and female volunteers BMI of 18-40 kg/m2 Aged 18-45 Volunteers who are willing to sign the consent form Exclusion Criteria: Healthy subjects unwilling to consent Smokers Known sensitivity to Racecadotril History of any serious illnesses, including recent infections or trauma A personal history of keloid scarring, or a family history of keloid scarring in a first degree relative with similar skin pigmentation Subjects taking systemic medication (other than the oral contraceptive pill) 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 Women who are breastfeeding Subjects with recent or current antibiotic use Subjects with a history of skins conditions. Subjects with a history of allergic reaction to any topical application or history of angioedema Subjects with any history of a blood-borne infectious disease such Hepatitis B or C virus, or HIV.

Sites / Locations

  • William Harvey Research Institute- Heart CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Racecadotril

Arm Description

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

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

Outcomes

Primary Outcome Measures

Powered unpaired inter-patient comparison of change in blister fluid volume following Racecadotril or placebo administration.
Powered paired intra-patient comparison of change in blister fluid volume following Racecadotril or placebo admininstration.

Secondary Outcome Measures

Powered comparison of sex differences in change in blister volume following Racecadotril or placebo administration.
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.
Comparison of change in blister fluid leukocyte count following Racecadotril or placebo administration
Comparison of change in pro and anti-inflammatory mediators from blister fluid following Racecadotril or placebo administration
Comparison of change in plasma cGMP following oral Racecadotril or placebo administration

Full Information

First Posted
October 3, 2022
Last Updated
September 12, 2023
Sponsor
Queen Mary University of London
Collaborators
Medical Research Council
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1. Study Identification

Unique Protocol Identification Number
NCT05600062
Brief Title
Influence of NEP Inhibition on Vascular Leak and Inflammation (NEPi-INFLAMMATION)
Official Title
Assessment of the Effect of Neutral Endopeptidase Inhibition on Vascular Leak and Leukocyte Accumulation in a Human Cantharidin Blister Model
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 24, 2023 (Actual)
Primary Completion Date
January 17, 2025 (Anticipated)
Study Completion Date
June 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Queen Mary University of London
Collaborators
Medical Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome
Keywords
ARDS, endothelium, CNP, Acute lung injury

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablet to be taken three times a day for three days
Arm Title
Racecadotril
Arm Type
Experimental
Arm Description
Racecadotril 100 milligrams (mg) three times a day for three days
Intervention Type
Drug
Intervention Name(s)
Racecadotril 100 milligram (MG) Oral Capsule
Other Intervention Name(s)
Tiorfan
Intervention Description
Licensed NEP inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsule
Primary Outcome Measure Information:
Title
Powered unpaired inter-patient comparison of change in blister fluid volume following Racecadotril or placebo administration.
Time Frame
24 hours after application of cantharidin
Title
Powered paired intra-patient comparison of change in blister fluid volume following Racecadotril or placebo admininstration.
Time Frame
24 hours after application of cantharidin
Secondary Outcome Measure Information:
Title
Powered comparison of sex differences in change in blister volume following Racecadotril or placebo administration.
Time Frame
End of study
Title
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.
Time Frame
24 hours after application of cantharidin
Title
Comparison of change in blister fluid leukocyte count following Racecadotril or placebo administration
Time Frame
24 hours after application of cantharidin
Title
Comparison of change in pro and anti-inflammatory mediators from blister fluid following Racecadotril or placebo administration
Time Frame
24 hours after application of cantharidin
Title
Comparison of change in plasma cGMP following oral Racecadotril or placebo administration
Time Frame
24 hours after application of cantharidin

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
Equal number of males and females
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy male and female volunteers BMI of 18-40 kg/m2 Aged 18-45 Volunteers who are willing to sign the consent form Exclusion Criteria: Healthy subjects unwilling to consent Smokers Known sensitivity to Racecadotril History of any serious illnesses, including recent infections or trauma A personal history of keloid scarring, or a family history of keloid scarring in a first degree relative with similar skin pigmentation Subjects taking systemic medication (other than the oral contraceptive pill) 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 Women who are breastfeeding Subjects with recent or current antibiotic use Subjects with a history of skins conditions. Subjects with a history of allergic reaction to any topical application or history of angioedema Subjects with any history of a blood-borne infectious disease such Hepatitis B or C virus, or HIV.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aemun Salam, MBBS, MRCP, FFICM
Phone
07492042830
Email
aemun.salam@qmul.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Hobbs
Organizational Affiliation
Queen Mary University London
Official's Role
Principal Investigator
Facility Information:
Facility Name
William Harvey Research Institute- Heart Centre
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aemun Salam
Email
aemun.salam@qmul.ac.uk

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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
IPD Sharing Time Frame
6 months after publication
IPD Sharing Access Criteria
Access requests can be made to the investigators by email

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

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