TranspulmonarY Estrogen Gradient and Estrogen Receptors (TYEGER) in PAH

NCT04280523 | Withdrawn FDA Drug

• 1 other identifier: 191946
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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. Update 12/31/2024: This record was updated to reflect the actual status of the research:

• The study was observational, as the 18F-FES PET was not an interventional procedure, but was planned to be used as an estrogen receptor (ESR)-specific PET tracer to determine lung ESR density.
• Zero participants were enrolled. Due to Covid-19, we utilized 66 serum samples from another study to test the hypothesis that among PAH patients, transpulmonary (TP) E2 gradient associates with a more severe hemodynamic profile and worse 1 year outcomes.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• To correlate lung ESR density with pulmonary vascular resistance (PVR)

  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.

  Day 1

Secondary Outcomes (1)

• Survival at one year

  1 year

Study Arms (1)

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

Interventions

ESR-specific PET scan DRUG

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.

Also known as: [18F]FES

ESR-specific PET Scan

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Group 1 pulmonary hypertension (PAH) patients compared to Group 2 PH (pulmonary venous hypertension, PVH) patients

You may qualify if:

• Age 13 years or older
• Group 3: Healthy Control Patients, who have no known history of cardiopulmonary disease recruited from the Vanderbilt Research Notification Distribution List and the population at large.

You may not qualify if:

• Subjects with the following concurrent diagnoses
• Type 1 Diabetes Mellitus
• Polycystic ovarian disease
• Breast/uterine/endometrial cancer
• Subjects with the following concurrent exposures
• Use of hormone modifying therapy
• Use of hormone-containing pharmaceuticals including hormone replacement therapy.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

16-fluoroestradiol

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Eric D Austin, MD, MSCI

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics, Director Vanderbilt Pediatric PH Program

Study Record Dates

• First Submitted: January 15, 2020
• First Posted: February 21, 2020
• Study Start: January 5, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: January 3, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

US (1)