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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 79

Contacts and Locations

Study Locations

• Brazil
  • Porto Alegre, Brazil, CEP 900050-170
    • Universidade Federal de Ciências da Saúde de Porto Alegre
• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be recruited from pulmonary circulation clinic (Brazil) and the Mayo Clinic (Cardiovascular Division) in Jacksonville, FL

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut-microbial dysbiosis	Identification of fecal microbiota and the function of the gut microbial community	3 weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Mayo Clinic; National Heart, Lung, and Blood Institute (NHLBI); Federal University of Health Science of Porto Alegre
• Investigators: Principal Investigator: Mohan Raizada, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2015
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Dysbiosis
• Other Study ID Numbers: IRB201900896 - N; R01HL102033 (U.S. NIH Grant/Contract); IRB# 16-001964 (Other Identifier: Mayo Clinic); CAAE: 44197015.0.0000.5327 (Other Identifier: Federal University of Health Sciences Porto Alegre, Brazil)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data for primary and secondary outcomes will be made available to other researchers
• IPD Sharing Time Frame: Data will be released a year after completion of the study and or publication of manuscripts containing the data as required by the journal and NIH guidelines.
• IPD Sharing Access Criteria: The sequence data will be deposited on publicly available sites.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No