Targeting Breathing Limitations to Improve Functional Outcomes in HFpEF

NCT ID: NCT05723679

Last Updated: 2025-04-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-01

Study Completion Date

2029-06-30

Brief Summary

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The overall purpose of this study is to investigate whether pulmonary limitations that increase the oxygen (O2) cost of breathing impact dyspnea on exertion (DOE) and peak exercise capacity in patients with HFpEF and obesity. As per investigator's hypothesis, obesity is likely a significant contributor to DOE and exercise intolerance in patients with HFpEF.

Detailed Description

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Clinical screening tests including cardiopulmonary exercise testing (CPET), pulmonary function testing, and dual-energy x-ray absorptiometry (DEXA) scans will be performed on all subjects. Investigator's approach will be to undertake the following objectives:

Objective 1: (Observational) is a cross-sectional study designed to test the interaction of HFpEF (underlying changes in pulmonary function) and obesity (obesity-related changes in pulmonary function) on the O2 cost of breathing, and its association with DOE and peak exercise capacity. The specific hypotheses proposed to test as part of this objective are:

Hypothesis 1.1: Due to the presence of obesity-related mechanical ventilatory constraints, the O2 cost of breathing will be greater in obese HFpEF patients and obese controls vs. nonobese HFpEF patients and nonobese controls, but will be similar between obese HFpEF patients vs. obese controls.

Hypothesis 1.2: The association between the O2 cost of breathing and DOE and the association between the O2 cost of breathing and peak exercise capacity will be stronger in obese HFpEF patients and obese controls vs. nonobese HFpEF patients and nonobese controls, but will be similar between obese HFpEF patients vs. obese controls.

Objective 2: (Interventional) is a single-blind, randomized, placebo-controlled, cross-over trial designed to investigate the effects of reducing obesity-related mechanical ventilatory constraints by breathing a HeO2 gas mixture (HeO2: 21% O2 and 79% He) on DOE and peak exercise capacity. The specific hypotheses proposed to test as part of this objective are:

Hypothesis 2.1: HeO2 will decrease DOE in obese HFpEF patients and obese controls, but not in nonobese HFpEF patients or nonobese controls, as HFpEF- or cardiovascular-related limitations will not be affected by HeO2.

Hypothesis 2.2: HeO2 will increase peak exercise capacity in obese HFpEF patients and obese controls, but not in nonobese HFpEF patients or nonobese controls as HFpEF- or cardiovascular-related limitations will not be affected by HeO2.

Study Day 1:

This visit consists of a consenting process (including medical Hx , DEXA scan, and pulmonary function testing. Goals of this day are to determine fat and lean mass and to quantify pulmonary function. This visit will usually last between 3 - 3.5 hours. Any subjects who demonstrate severe pulmonary disease at this point will be excluded.

Study Day 2:

This visit will consist of O2 cost of breathing tests, as well as submaximal and maximal CPET tests. This visit is designed to test Hypotheses 1.1 and 1.2. and will usually last between 3 - 3.5 hours.

Study Day 3 and 4:

These visits consist of submaximal and maximal CPET tests with either breathing room air or HeO2 gas mixtures on separate days. These visits are designed to test Hypotheses 2.1 and 2.2. and will usually last between 2 - 2.5 hours.

The Diagnostic test including : 1) Submaximal and maximal cardiopulmonary exercise test 2) pulmonary function testing 3) Eucapnic Voluntary Hyperventilation 3) Dual-Energy X-Ray absorptiometry (DEXA), are the procedures that will be performed by the participants for investigator to gather data (observational) and assess DOE, peak exercise capacity, pulmonary function, body composition, and O2 cost of breathing between study groups.

Conditions

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Heart Failure With Preserved Ejection Fraction Obesity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Mechanistic Clinical Trial
Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Participants
The order of the room air and HeO2 tests will be randomized and the subjects will not be told what gas mixture they will be breathing.

Study Groups

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HeO2 gas mixture, then Room air gas mixture

Participant will be randomized to each intervention on separate days (Study visit 3 and 4) in this cross-over trial. Participants that receive HeO2 first will then receive the room air gas mixture. At least 24 hours will separate each visit.

Group Type EXPERIMENTAL

HeO2 gas mixture

Intervention Type OTHER

Low-density helium-oxygen gas mixture (HeO2: 21% O2 and 79% He). Participant will be breathing this gas mixture.

Room air gas mixture

Intervention Type OTHER

Normal room air

Room air gas mixture, then HeO2 gas mixture

Participant will be randomized to each intervention on separate days (Study visit 3 and 4) in this cross-over trial. Participants that receive Room air first will then receive the HeO2 mixture. At least 24 hours will separate each visit.

Group Type EXPERIMENTAL

HeO2 gas mixture

Intervention Type OTHER

Low-density helium-oxygen gas mixture (HeO2: 21% O2 and 79% He). Participant will be breathing this gas mixture.

Room air gas mixture

Intervention Type OTHER

Normal room air

Interventions

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HeO2 gas mixture

Low-density helium-oxygen gas mixture (HeO2: 21% O2 and 79% He). Participant will be breathing this gas mixture.

Intervention Type OTHER

Room air gas mixture

Normal room air

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* signs and symptoms of heart failure
* an ejection fraction \> 0.50;
* objective evidence of diastolic dysfunction. elevated biomarkers (NT-proBNP \>300 ng/dl) or HF hospitalization
* healthy volunteers

Exclusion Criteria

* age \< 55 years
* BMI \> 50 kg/m2
* Atrial fibrillation with poorly controlled heart rate
* phosphodiesterase type 5 (PDE5) inhibitor use
* severe valvular disease
* severe Chronic obstructive pulmonary disease (COPD)
* Chronic kidney disease (CKD) 4 or higher
* any restriction of ambulation and mobility.
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Bryce Balmain

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tony G Babb, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Bryce N Balmain, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

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UT Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Raksa B Moran, RN

Role: CONTACT

214-345-6574

Jessica N Alcala, RN

Role: CONTACT

214-345-6574

Facility Contacts

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Raksa B Moran, RN

Role: primary

214-345-6574

Jessica N Alcala, RN

Role: backup

2143456574

Other Identifiers

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STU-2022-1174

Identifier Type: -

Identifier Source: org_study_id

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