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

Phase 1
Completed
Conditions
Heart Failure, Congestive
Registration Number
NCT01277679
Lead Sponsor
GlaxoSmithKline
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Lung water distribution as measured by MRIVisit 1 and Visit 2 will be approximately 1 week apart

MRI test

Lung water concentration as measured by MRIVisit 1 and Visit 2 will be approximately 1 week apart

MRI test

Secondary Outcome Measures
NameTimeMethod
Between patient variability in lung water concentration as measured by MRI at 2 independent visitsVisit 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 visitsVisit 1 and Visit 2 will be approximately 1 week apart

MRI test

Trial Locations

Locations (1)

GSK Investigational Site

🇬🇧

London, United Kingdom

GSK Investigational Site
🇬🇧London, United Kingdom

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