TranspulmonarY Estrogen Gradient and Estrogen Receptors (TYEGER) in PAH (TYEGER)
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|ClinicalTrials.gov Identifier: NCT04280523|
Recruitment Status : Recruiting
First Posted : February 21, 2020
Last Update Posted : January 20, 2021
Pulmonary arterial hypertension (PAH) is a disease characterized by elevated pressures in the blood vessels of the lungs that is not caused by another disease processes. More specifically, it is defined by a mean pulmonary artery pressure > 25 mm Hg, a pulmonary vascular resistance > 3 Wood Units (WU), and a normal pulmonary capillary wedge pressure in the absence of other etiology of pulmonary hypertension. The underlying mechanism of the disease in still unknown, but marked changes to the small arteries in the lungs have been observed. These changes include thickening of vessel walls and clot formation -- making the vessels less capable of gas exchange. Currently, PAH therapies focus on dilating the "good" remaining vessels that haven't been altered by this disease process; however, this therapy does not cure the disease. Survival remains low despite progress.
There is growing human and experimental evidence supporting the concept that estrogens and estrogen receptors in the lungs are involved in the process that leads to PAH.
As mentioned above, no current therapies attack the cause of PAH; they only act to dilate remaining "good" vessels which can reduce the burden of the disease, but not cure it. Thus, there is a critical need for novel therapeutics, as recently highlighted by a National Institute of Health workshop on pulmonary vascular diseases which called for the exploration of novel therapeutic approaches. None of the current FDA-approved treatments for PAH target estrogen or estrogen receptors.
Despite the evidence supporting the concept that estrogens and estrogen receptors in the lungs contribute to PAH, no human studies investigate the estrogen level and the amount of estrogen receptors within the lungs of patients with PAH and their potential associations with current disease severity or 1 year outcomes including survival after 1 year, functional status, etc. Investigators hypothesize that a subset of PAH patients will have higher levels of estrogen and estrogen receptors in their lungs which would make them good candidates for novel therapies that block estrogen in hopes of halting the disease process.
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Arterial Hypertension||Drug: ESR-specific PET scan||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||TranspulmonarY Estrogen Gradient and Estrogen Receptors (TYEGER) in PAH|
|Actual Study Start Date :||January 5, 2021|
|Estimated Primary Completion Date :||October 2024|
|Estimated Study Completion Date :||October 2024|
Experimental: ESR-specific PET Scan
Specific Aim: To test the hypothesis that among PAH patients, higher lung ESR density associates with a more severe hemodynamic profile and worse 1 year outcomes.
Study Design: Enroll 20 randomly selected subjects from each group (PAH vs. control)
Drug: ESR-specific PET scan
Lung ESR Density by PET: Investigators will use 18F-FES as an estrogen receptor (ESR)-specific PET tracer to determine lung ESR density. 18F-FES will be prepared according to published methods. Briefly, all subjects will be evaluated by PET imaging, using standardized protocols. Blood will be obtained just before FES injection to measure the endogenous estrogen level [estradiol (E2)], to rule out pregnancy in female patients, and some reserved for future studies of mechanism. Approximately 6 mCi (222 MBq) of 18F-FES will be administered intravenously over 1~2 minutes, with scanning initiated 1 hour after administration of the tracer. Emission scans will be performed of the chest. A multimodality computer platform (Syngo; Siemens) will be used for image review and manipulation.
Other Name: [18F]FES
- To correlate lung ESR density with pulmonary vascular resistance (PVR) [ Time Frame: Day 1 ]Positron emission tomography (PET) with ESR-targeting radiopharmaceuticals is a noninvasive method for assessing regional ESR expression in vivo. For example, multiple studies have shown that the detection of ESR positive tissue by 18F-FES PET is reliable and that 18F-FES uptake correlates well with immunohistochemical scoring for ESR density. We will determine the relationship, if any, between the density of ESR in the lungs of subjects, and pulmonary vascular resistance (PVR), measured in Woods Units, acquired at time of recent cardiac catheterization.
- Survival at one year [ Time Frame: 1 year ]We will determine the association of lung ESR density with survival within one year of the PET scan study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04280523
|Contact: Eric D Austin, MD, MSCI||(615) firstname.lastname@example.org|
|Contact: Jeff Cunningham, RN||(615) email@example.com|
|United States, Tennessee|
|Vanderbilt University Medical Center||Recruiting|
|Nashville, Tennessee, United States, 37203|
|Contact: Eric D Austin, MD, MSCI 615-343-7396 firstname.lastname@example.org|
|Principal Investigator:||Eric D Austin, MD, MSCI||Vanderbilt University Medical Center|