Look at Way the Heart Functions in People With Pulmonary Hypertension (PH) Who Have Near Normal Right Ventricle (RV) Function and People With Pulmonary Hypertension Who Have Impaired RV Function. Using Imaging Studies PET Scan and Cardiac MRI.

Pulmonary Arterial Hypertension Clinical Trial

Official title:

11C-acetate/18Fluorodeoxyglucose-FDG PET/Cardiac MRI in Pulmonary Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01953965
• Other study ID #: CMREF-PH Imaging
• Status: Terminated
• Phase: Phase 2
• First received: September 26, 2013
• Last updated: July 27, 2016
• Start date: September 2013
• Est. completion date: July 2016

Study information

• Verified date: July 2016
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study to look at differences in the way the heart functions in people with pulmonary hypertension (PH) who have near normal right ventricle (RV) function and people with pulmonary hypertension who have impaired RV function. The right ventricle is a chamber of the heart that pumps blood into the pulmonary artery (the artery that carried blood from the heart to the lungs). Learning more about how the heart is working in people with pulmonary hypertension may help researchers to understand how to better treat pulmonary hypertension and prevent the disease from getting worse.

To do this, we will use two imaging techniques, MRI (Magnetic Resonance Imaging) and PET/CT (Positron Emission Tomography/Computed Tomography). MRI uses a strong magnet and radio waves to take pictures of your heart. A PET/CT scan combines a PET and CT scan into one machine. A CT scan uses x-0rays to take a 3-day picture of the inside of your body, while a PET scan measures small amounts of radiation from a dye called a "tracer" that we inject into your veins.

You will be given two tracers as part of the PET/CT scan. A tracer is a special type of dye with a small amount of radioactivity in it. The tracers that are used in this study are called [18F]fluorodeoxyglucose (FDG) and [11C]-acetate.

In order to take part in this study, you must also have agreed to take part in a companion study. In the companion study, we are trying to learn whether the drug ranolazine is safe and effective in people with PH.

Description:

Historically, RV failure had been described as a stereotyped response to hemodynamic overload. More recent large patient cohort data suggests that RV, independently from Pulmonary Arterial Pressure (PAP), predicts mortality. Thus, a recent hypothesis suggests that individual genetic differences dysregulate cardiomyocyte function and, in doing so, predispose to RV failure in humans, control patient-specific manifestations of disease, and thus would represent key diagnostic markers and therapeutic targets. In fact, multiple key metabolic regulatory factors have been found to be altered in RV failure, any one of which could contribute to individual predisposition to RV failure. Based on their established functions in left ventricular injury and metabolism19 and known alterations in right ventricular failure20, we propose to evaluate metabolic dysfunction of the RV using positron emission topography (PET) and cardiac magnetic resonance imaging (CMR).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: July 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

Inclusion Criteria:

• Participation in the companion treatment protocol "A randomized, double-blind, placebo-controlled, multi-center study to assess the effect of ranolazine on outcomes in subjects with pulmonary hypertension and right ventricular dysfunction accompanied by a comparative study of cellular metabolism in subjects with pulmonary hypertension with and without right ventricular dysfunction".

Exclusion Criteria:

• Pregnancy or lactation: Women of childbearing potential must have a negative urine or blood pregnancy test on the day of the PET/CT scan.

• Anxiety or claustrophobia prohibiting completion of imaging

• Inability to tolerate imaging procedures (up to 2 hours on scanner)

• Moderate to severe chronic renal disease defined as an estimated glomerular filtration rate < 30 ml/min/1.73m2

• Implantable cardioverter-defibrillator, pacemaker, hazardous metallic implants or any other contraindication to MRI

• History of uncontrolled diabetes mellitus with fasting glucose > 150 mg/dL at the treatment protocol screening visit.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Familial Primary Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Arterial Hypertension

Intervention

Drug:
• 11C-acetate
For each PET/CT imaging session subject will receive a 15-25 millicurie intravenous injection of 11C-acetate
• [18F]Fluoro-2-deoxy-2-D-glucose
For each PET/CT imaging session subjects will receive a 10 millicurie injection of 18F-FDG
• MultiHance
Cardiac MRI is performed at 6 months to measure any change in structure and function of the treatment groups. MultiHance is the contrast that will be given to subjects.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	University of Maryland, University of Pennsylvania, Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. To demonstrate that there are differences in metabolism and function between subjects with near normal RV function and persistent RV dysfunction as defined by CMR Right Ventricular Ejection Fraction (RVEF) of <= 40%.	Compare myocardial oxygen consumption, FDG uptake, and myocardial perfusion at baseline for subjects with near normal right ventricular function and those with persistent right ventricular dysfunction.	baseline and 6 months	No
Primary	2. To measure changes in RV energy and contractility in subjects with persistent RV dysfunction using serial 11C-acetate and 18F-FDG PET/CT and CMR. perfusion	Compare myocardial oxygen consumption, FDG uptake, and myocardial perfusion at baseline for subjects with near normal right ventricular function and those with persistent right ventricular dysfunction.	Baseline to 6 months	No
Secondary	Changes in myocardial structure and function	Using CMR, comparing myocardial structure and function in patients treated with ranolazine or placebo.	6 months	No