Evaluation of MRI Measures of Lung Water With Posture Changes in Healthy Volunteers and in Patients With Cardiac Failure

Study Overview
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Brief Summary
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The aim of this study is to establish a model for the evaluation of drug targets using postural measures to induce changes in lung water concentration as assessed by MRI. A reduction in the magnitude and rate of water transudation with postural changes in patients with congestive heart failure (CHF) could provide a model for the evaluation of various classes of molecules for target validation and for dose selection.

Official Title
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An Evaluation of MRI Measures of Lung Water Increases With Postural Changes in Healthy Subjects and in Patients With Cardiac Failure: A Methods Validation Study for Evaluation of Novel Treatments Limiting Pulmonary Oedema in Cardiac Failure

Conditions
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Heart Failure, Congestive

Intervention / Treatment
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* Procedure: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heart Failure Patients: Established diagnosis of mild to moderate heart failure of any aetiology with symptoms defined as corresponding to the New York Heart Association (NYHA) class I, II or III Able in the opinion of the patient and investigator to be supine for 1 hour and to experience passive leg raising (PLR) whilst in the MRI scanner Male or female over 18 years of age at the time of signing the informed consent Negative urine or serum pregnancy test Capable of giving written informed consent Registered with a UK general practitioner. Participants must read (in English) at a level sufficient to adequately complete study related questionnaires Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions Healthy Volunteers: Healthy as determined by a responsible physician Male or female over 18 years of age at the time of signing the informed consent Capable of giving written informed consent Negative urine or serum pregnancy test Registered with a UK general practitioner Participants must read (in English) at a level sufficient to adequately complete study related questionnaires Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions Exclusion Criteria: Heart Failure Patients History of primary pulmonary disease requiring current medication or other therapy. Orthopnoea of sufficient severity to preclude supine scanning. Hip or leg pathology of sufficient severity to prevent extension of both legs to 45 degrees. Unstable heart failure, defined as change in NYHA status, change in heart failure therapy regimen or hospitalization for acute decompensation of heart failure within preceding 6 weeks. Unstable angina within the past 3 months Current smoker, defined as having smoked in the preceding 1 year Uncontrolled hypertension (resting systolic BP > 160 mmHg or resting diastolic BP > 100mmHg) Resting hypoxia (SaO2 <93%). Contraindication to MRI scanning Pregnant females Positive drugs of abuse or alcohol screen. Unwillingness or inability to follow the procedures outlined in the protocol. Healthy Volunteers History of primary pulmonary disease requiring current medication or other therapy Current smoker, defined as having smoked in the preceding 1 year Hip or leg pathology of sufficient severity to prevent extension of both legs to 45 degrees Contraindication to MRI scanning Pregnant females Positive drugs of abuse or alcohol screen Unwillingness or inability to follow the procedures outlined in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Healthy Volunteer<br>Healthy Volunteer cohort | Procedure: MRI<br>* MRI of lungs to measure lung water content before and after passive leg raising (PLR)<br>|
| Other: Heart Failure<br>Heart Failure cohort | Procedure: MRI<br>* MRI of lungs to measure lung water content before and after passive leg raising (PLR)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung water distribution as measured by MRI | MRI test | Visit 1 and Visit 2 will be approximately 1 week apart | 
| Lung water concentration as measured by MRI | MRI test | Visit 1 and Visit 2 will be approximately 1 week apart | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between patient variability in lung water concentration as measured by MRI at 2 independent visits | MRI test | Visit 1 and Visit 2 will be approximately 1 week apart | 
| Within patient variability in lung water concentration as measured by MRI at 2 independent visits | MRI test | Visit 1 and Visit 2 will be approximately 1 week apart | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, lung water measures, pulmonary edema, heart failure