TranspulmonarY Estrogen Gradient and Estrogen Receptors (TYEGER) in PAH

• Status: Recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Treatments: Estrogens

Criteria

Inclusion Criteria:

• Age 13 years or older

• Group 1: PH Patients, who have precapillary PH (PAH). Patients with and without a known PAH-associated gene mutation (e.g., a BMPR2 mutation) (i.e. those with HPAH and those with IPAH) will be identified based on previous genotyping. Investigators define pulmonary hypertension diagnostically by accepted clinical and cardiac catheterization criteria, including mean pulmonary arterial pressure of more than 25 mmHg. Precapillary PH (PAH) cases have pulmonary capillary or left atrial pressure of ≤15 mm Hg, and exclusion of other causes of pulmonary hypertension in accordance with accepted international standards of diagnostic criteria.

• Group 2: PVH Patients, who have pulmonary hypertension secondary to left heart disease. PVH cases have left ventricular (LV) filling pressure >15 mmHg (measured by the pulmonary artery occlusion pressure or left ventricular end-diastolic pressure) and a diastolic pressure gradient <7mmHg, indicating the absence of pulmonary vascular disease. Inclusion in this group will require a clinical diagnosis of systolic or diastolic heart failure and right heart catheterization on at least one occasion demonstrating elevated pulmonary wedge pressure and a normal (< 16mmHg) trans-pulmonary gradient

• 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.

Exclusion Criteria:

1. Subjects with the following concurrent diagnoses

• Type 1 Diabetes Mellitus

• Polycystic ovarian disease

• Breast/uterine/endometrial cancer

2. Subjects with the following concurrent exposures

• Use of hormone modifying therapy

• Use of hormone-containing pharmaceuticals including hormone replacement therapy.