Heart Failure, Congestive
Conditions
Keywords
lung water measures, pulmonary edema, MRI, heart failure
Brief summary
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.
Interventions
PROCEDUREMRI
MRI of lungs to measure lung water content before and after passive leg raising (PLR)
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lung water distribution as measured by MRI | Visit 1 and Visit 2 will be approximately 1 week apart | MRI test |
| Lung water concentration as measured by MRI | Visit 1 and Visit 2 will be approximately 1 week apart | MRI test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Between patient variability in lung water concentration as measured by MRI at 2 independent visits | Visit 1 and Visit 2 will be approximately 1 week apart | MRI test |
| Within patient variability in lung water concentration as measured by MRI at 2 independent visits | Visit 1 and Visit 2 will be approximately 1 week apart | MRI test |
Countries
United Kingdom
Outcome results
None listed