Ignite Creation Date:
2024-05-06 @ 10:07 AM
Last Modification Date:
2024-10-26 @ 12:25 PM
Study NCT ID:
NCT03166306
Status:
COMPLETED
Last Update Posted:
2021-05-06
First Post:
2017-05-09
Brief Title:
Angiogenic Imaging in Pulmonary Arterial Hypertension
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
Angiogenic Imaging in Pulmonary Arterial Hypertension
Status:
COMPLETED
Status Verified Date:
2021-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AIPAH
Brief Summary:
Pulmonary arterial hypertension PAH is a disorder of elevated pulmonary vascular resistance characterized by progressive remodeling and obliteration of vessels of the distal pulmonary circulation Outcomes in PAH could be improved with earlier diagnosis and with the early deployment of therapies before irreversible changes have occurred This study tests the sensitivity of positron emission tomography PET-CT scanning with 89Zr-bevacizumab a radioisotope-conjugated anti-VEGF antibody for detecting pulmonary vascular remodeling in PAH disease This test could enable non-invasive diagnosis early in the course of the disease and potentially improve outcomes in PAH
Detailed Description:
PAH is a disease of progressive remodeling and obliteration of the distal pulmonary vasculature The overexpression of VEGF-A in the pulmonary vasculature of patients with PAH and animal models of disease is thought to reflect a process of disordered angiogenesis that is tightly coupled to disease progression It is hypothesized that positron emission tomography PET-CT scan utilizing 89Zr-bevacizumab a radioisotope-conjugated humanized monoclonal antibody against VEGF-A would provide a sensitive and specific molecular imaging modality to detect pulmonary vascular remodeling activity
To test this hypothesis the investigators propose a Phase III pilot study to enroll 10 patients with known severe idiopathic or familial PAH 10 individuals with exercise-associated PAH EPAH thought to be a mild and early stage of PAH and 10 healthy volunteers with no evidence of cardiopulmonary disease This pilot study will compare standardized uptake values SUV for the retention of 89Zr-bevacizumab in the distal pulmonary vasculature in these three populations The kinetics of equilibration and wash-out of this probe will be assessed with sequential scans at 4 and 7 days following the injection of radionuclide In patients with PAH or EPAH repeat scans will be performed 1 year after the initial scan to assess whether changes in clinical status correlate with 89Zr-bevacizumab retention
The ability of these protocols to discriminate between the lungs of healthy individuals versus patients with PAH or EPAH will be evaluated using the measure of peripheral lung tissue probe SUV corresponding to distal pulmonary vessel uptake normalized to the proximal aortic SUV corresponding to the blood pool These data will be used to define normative values for healthy controls versus PAH patients and to generate cutoffs in signaling ratios with optimal sensitivity and specificity for disease detection These normative ranges will be applied to the EPAH cohort to determine if this test retains sensitivity and specificity for a potentially milder earlier form of PAH
This study is divided into 4 Aims
AIM 1 Test the hypothesis that expression of VEGF-A discerned by 89Zr-bevacizumab imaging is increased in the distal pulmonary vascular bed in PAH patients compared to healthy individuals
AIM 2 Test the hypothesis that expression of VEGF-A discerned by 89Zr-bevacizumab imaging is increased in the distal pulmonary vascular bed in patients with exercise-associated PAH compared to healthy individuals
AIM 3 Ascertain whether or not distal pulmonary vascular uptake of 89Zr-bevacizumab correlates with clinical markers of PAH severity including 6 minute walk distance New York Heart Association functional class right atrial pressure mean pulmonary artery pressure pulmonary vascular resistance cardiac index NT-proBNP tricuspid annular plane systolic excursion TAPSE by echocardiography
AIM 4 Ascertain whether or not changes in distal pulmonary vascular uptake of 89Zr-bevacizumab over 1 year in patients with PAH or EPAH correlates with changes in clinical status based on clinical markers of PAH severity
To test this hypothesis the investigators propose a Phase III pilot study to enroll 10 patients with known severe idiopathic or familial PAH 10 individuals with exercise-associated PAH EPAH thought to be a mild and early stage of PAH and 10 healthy volunteers with no evidence of cardiopulmonary disease This pilot study will compare standardized uptake values SUV for the retention of 89Zr-bevacizumab in the distal pulmonary vasculature in these three populations The kinetics of equilibration and wash-out of this probe will be assessed with sequential scans at 4 and 7 days following the injection of radionuclide In patients with PAH or EPAH repeat scans will be performed 1 year after the initial scan to assess whether changes in clinical status correlate with 89Zr-bevacizumab retention
The ability of these protocols to discriminate between the lungs of healthy individuals versus patients with PAH or EPAH will be evaluated using the measure of peripheral lung tissue probe SUV corresponding to distal pulmonary vessel uptake normalized to the proximal aortic SUV corresponding to the blood pool These data will be used to define normative values for healthy controls versus PAH patients and to generate cutoffs in signaling ratios with optimal sensitivity and specificity for disease detection These normative ranges will be applied to the EPAH cohort to determine if this test retains sensitivity and specificity for a potentially milder earlier form of PAH
This study is divided into 4 Aims
AIM 1 Test the hypothesis that expression of VEGF-A discerned by 89Zr-bevacizumab imaging is increased in the distal pulmonary vascular bed in PAH patients compared to healthy individuals
AIM 2 Test the hypothesis that expression of VEGF-A discerned by 89Zr-bevacizumab imaging is increased in the distal pulmonary vascular bed in patients with exercise-associated PAH compared to healthy individuals
AIM 3 Ascertain whether or not distal pulmonary vascular uptake of 89Zr-bevacizumab correlates with clinical markers of PAH severity including 6 minute walk distance New York Heart Association functional class right atrial pressure mean pulmonary artery pressure pulmonary vascular resistance cardiac index NT-proBNP tricuspid annular plane systolic excursion TAPSE by echocardiography
AIM 4 Ascertain whether or not changes in distal pulmonary vascular uptake of 89Zr-bevacizumab over 1 year in patients with PAH or EPAH correlates with changes in clinical status based on clinical markers of PAH severity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None