Angiotensin Converting Enzyme (ACE2), Brain, Gut Dysbiosis in Pulmonary Hypertension

University of Florida

Status: Completed

Conditions: Pulmonary Arterial Hypertension

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT04104490

IRB201900896 - N

IRB# 16-001964 (Other Identifier)

CAAE: 44197015.0.0000.5327 (Other Identifier)

R01HL102033 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Pulmonary arterial hypertension (PAH) is fatal with right heart failure due to raised pulmonary vascular pressure. Gut dysbiosis was identified in animals with pulmonary hypertension. Deidentified human samples will be tested for gut dysbiosis in PAH, circulating bacterial metabolites and markers of inflammation and gut leakiness. The gut microbiome and circulating metabolites, markers of inflammation and gut leakiness of PAH patients and healthy subjects will be compared in deidentified fecal samples and blood.

Full description

Stool samples will be collected from people with no, mild-moderate or severe pulmonary arterial hypertension. Bacterial DNA will be extracted from the feces and sequenced by whole genome sequencing (shotgun sequencing). The DNA sequences will be used to identify the bacteria present in the feces, and to model the functions of the gut microbial community in each of the three groups. This will test for gut dysbiosis in pulmonary arterial hypertensive patients compared to healthy subjects. Gut dysbiosis is a condition where the gut bacterial communities are unbalanced and has been implicated in disease processes.

In subjects recruited in the USA, blood samples will be tested for markers of gut leakiness and inflammation as well as gut bacterial metabolites found in the circulation.

Enrollment: 79 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• severe, mild-moderate or no pulmonary arterial hypertensive subjects

Exclusion criteria

• Patients with pulmonary hypertension due to left heart disease, lung diseases and / or hypoxia, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension with unclear multifactorial mechanisms.

Trial design

79 participants in 3 patient groups

Severe pulmonary arterial hypertension.

Description:

This cohort will consist of patients with severe pulmonary arterial hypertension. This is defined as mean pulmonary arterial pressure 25 mm Hg or greater and pulmonary artery occlusion pressure 15 mmHg or less measured by right cardiac catheterization and a clinical diagnosis of severe disease. Participants will be without signs of left heart disease, lung disease and or hypoxia, chronic thromboembolic pulmonary hypertension or pulmonary hypertension of unclear multifactorial mechanisms. This is an observational study with no interventions.

Mild-moderate pulmonary arterial hypertension

Description:

This cohort will consist of patients with mild-moderate pulmonary arterial hypertension. This is defined as mean pulmonary arterial pressure 25 mm Hg or greater and pulmonary artery occlusion pressure 15 mmHg or less measured by right cardiac catheterization and a clinical diagnosis of mild-moderate disease. Participants will be without signs of left heart disease, lung disease and or hypoxia, chronic thromboembolic pulmonary hypertension or pulmonary hypertension of unclear multifactorial mechanisms. This is an observational study with no interventions.

Reference subjects without pulmonary hypertension

Description:

Reference subjects will be healthy people, age- and sex-matched to the other two cohorts, who have no pulmonary artery hypertension.