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

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure, Congestive
• Intervention / Treatment: Procedure: MRI

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: November 18, 2010
• First Submitted That Met QC Criteria: January 13, 2011
• First Posted (Estimate): January 17, 2011

Study Record Updates

• Last Update Posted (Estimate): June 2, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: MRI; heart failure; lung water measures; pulmonary edema
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Heart Failure; Pulmonary Edema
• Other Study ID Numbers: 114747

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No