- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03340233
Understanding the Mechanisms of Diastolic Dysfunction
April 29, 2019 updated by: Daniel Ennis, PhD, University of California, Los Angeles
A New Framework for Understanding the Mechanism of Diastolic Dysfunction
Heart failure is a clinical syndrome marked by breathlessness, even at low levels of exertion, general fatigue, and fluid retention and is estimated to affect 5.1 million people in the United States.
Heart failure with preserved ejection fraction (HFpEF) means that the heart pumps enough blood to the body, but patients still have terrible symptoms.
It is estimated to account for about 50% of all heart failure cases.
Experts agree that impaired filling of the heart, perhaps due to "stiffness" of the heart muscle itself, critically underlies HFpEF.
There is currently no clinical technique for measuring heart muscle (myocardial) stiffness; the very definition of "myocardial stiffness" remains poorly established.
Consequently, the ability to study the mechanisms that underlie HFpEF is virtually non-existent, and limited treatment options will persist without significant advances.
The objective of this project is to use an Equilibrium-Material-Stability (EMS) framework that couples patient-specific clinical MRI and heart pressure data in a computational model of the heart to diagnose changes in myocardial stiffness.
The central hypothesis is that the new EMS framework for understanding the mechanisms of diastolic dysfunction in HFpEF will be more sensitive and outperform currently available approaches.
Study Overview
Status
Withdrawn
Detailed Description
The study has three aims.
The first aim of the project is to refine MRI techniques using "free-breathing" versus "breath-holding" measurements.
Twenty-five normal volunteers will undergo MRI to refine "free-breathing" cardiac imaging and enable construction of patient-specific computer models of the heart.
The second aim of the project is to validate and test the myocardial stiffness evaluation framework derived through the first objective in human subjects.
Twenty-five normal volunteers will undergo MRI and the data from these images will be compared to specially constructed 3D printed models of the heart, enabling refinement of the EMS framework to separate structural stiffness from material stiffness.
The third aim of the project is to measure changes in myocardial stiffness in patients with HFpEF.
Thirty-three subjects with current diagnostic criteria for HFpEF will be evaluated at baseline and at six months to evaluate myocardial stiffness and cardiac MRI biomarkers.
Specifically, this aim will establish the diagnostic sensitivity of the EMS framework with comparison to cardiac MRI biomarkers of increased stiffness, thereby providing mechanistic insight to one critical underlying cause of HFpEF.
Study Type
Interventional
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
-
Los Angeles, California, United States, 90024
- University of California Los Angeles
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
Healthy volunteers
1. Healthy adults
Patients with Heart Failure with Preserved Ejection Fraction
- Patient scheduled for catheterization at UCLA Medical Center
- Ejection fraction >/= 50%
- Signs and symptoms of heart failure
- Excluded other potential non-cardiac etiologies of heart failure
Exclusion Criteria:
Healthy volunteers
- Known medical condition that impacts heart health
- Contraindications to MRI (e.g., pacemaker/ICD, or claustrophobia)
Patients with Heart Failure with Preserved Ejection Fraction
Exclusion Criteria:
- Contraindications to MRI (e.g., pacemaker/ICD, or claustrophobia)
- Prior MI or history of PCI/CABG
- Worse than mild valvular disease
- Any indication for ICD implantation
- Contraindication to MRI contrast agents or eGRF <30 ml/min/1.73m2 or MRI exams (e.g., pacemaker/ICD or claustrophobia).
- Atrial fibrillation or unstable cardiac rhythm
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1
Group 1 includes 25 healthy subjects recruited in Year 1 to undergo cardiac MRI without contrast.
|
MRI without contrast
|
Experimental: Group 2
Group 2 includes 25 healthy subjects recruited in Year 2 to undergo cardiac MRI without contrast.
|
MRI without contrast
|
Experimental: Group 3
Group 3 includes 33 patients with Heart Failure with Preserved Ejection Fraction (HFpEF) who will undergo cardiac MRI at baseline and at six months to assess diagnostic sensitivity of MRI measurement.
|
Clinical MRI
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The sensitivity of the EMS framework with comparison to cardiac MRI biomarkers of increased stiffness, thereby providing mechanistic insight to one critical underlying cause of HFpEF.
Time Frame: Five years
|
Assess the diagnostic sensitivity of MRI method by analyzing baseline and six month longitudinal characteristics in myocardial stiffness measured in patients with HFpEF
|
Five years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Daniel J Ennis, PhD, University of California, Los Angeles
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
June 1, 2018
Primary Completion (Anticipated)
September 1, 2021
Study Completion (Anticipated)
August 1, 2022
Study Registration Dates
First Submitted
November 8, 2017
First Submitted That Met QC Criteria
November 8, 2017
First Posted (Actual)
November 13, 2017
Study Record Updates
Last Update Posted (Actual)
May 1, 2019
Last Update Submitted That Met QC Criteria
April 29, 2019
Last Verified
April 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB#17-000695
- 1R01HL131823-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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