NCT02135861

A Method Validation Study for Evaluation of Novel Treatments Limiting Pulmonary Oedema in Cardiac Failure

An Evaluation of DCE-MRI Measures of Pulmonary Oedema and Vascular Permeability in Healthy Subjects and in Patients With Cardiac Failure: A Methods Validation Study for Evaluation of Novel Treatments Limiting Pulmonary Oedema in Cardiac Failure

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

Transient receptor potential vanilloid 4 (TRPV4) channel blockade may be promising in the treatment of pulmonary oedema and dyspnoea in heart failure (HF) and acute decompensated heart failure (ADHF) patients by re-establishing the alveolar septal barrier. Dynamic contrast enhanced (DCE) Magnetic Resonance Imaging (MRI) is an established technique for assessing changes in vascular permeability and interstitial water volume. The aim of this study is to establish the potential utility of DCE-MRI as a novel endpoint for dose ranging and proof of mechanism studies of TRPV4 blockers. The DCE-MRI markers of vascular permeability and pulmonary oedema will be measured in subjects with HF (group 2) and healthy volunteers (HV) (group 1) at rest to determine if there is a difference between the two populations. Apart from this, exercise induced changes relative to rest in interstitial volume and exchange rate will be evaluated in both HV and subjects with HF. Additionally, the capability of DCE-MRI to detect changes in interstitial lung fluid in patients with acute decompensated heart failure (ADHF) (group 3) will be investigated. DCE-MRI markers of pulmonary oedema will be assessed when patients are initially hospitalized with ADHF and subsequently after receiving standard of care treatment to determine whether differences can be detected by this methodology.This study will enrol a sufficient number of subjects to have at least 24 subjects in Group 1 and 2 (group 1:12 HV and group 2: 12 subjects with HF) and atleast 5 subjects in Group 3. For each subject, the MRI data must be of sufficient quality to enable DCE-MRI modelling from 2 Sessions. For group 1 and 2, the subjects will have screening visit and 3 MRI sessions. For the first scanning session, subjects will undergo the baseline procedure. The second imaging session will occur approximately one week later to measure within subject variability. A third imaging session (which will be conducted in 2 visits) will incorporate a bicycle exercise challenge prior to the MRI scan, and this third scan will be performed approximately one to three days after the second imaging session. For group 3: Screening will occur during hospitalization for eligibility. Session 1of MRI will be conducted while the subject is still hospitalized. Session 2 will be conducted within 4 weeks of the first scan, when the signs of pulmonary oedema are considered to be resolved. If a subject's pulmonary oedema has not resolved at Session 2, then the subject will be not be scanned by MRI at Session 2 and will be brought back for Session 3 up to 4 weeks after Session 2 for their second MRI.

Conditions

• Heart Failure, Congestive

Interventions

Type	Name	Description
PROCEDURE	DCE-MRI scans	Subjects will be placed supine in the scanner and will be prepared for intravenous contrast agent administration. The contrast agent is administered using a power injector before imaging.
OTHER	Gadobutrol	Gadobutrol at a dose less than or equal to 0.1 millimoles per kilogram (mmol/kg) will be given intravenously as a bolus using a power injector.

Timeline

• Start date: 2014-07-30
• Primary completion: 2017-02-22
• Completion: 2017-02-22
• First posted: 2014-05-12
• Last updated: 2019-02-27
• Results posted: 2019-02-27

Locations

1 site across 1 country: United Kingdom