Clinical trial NCT05723679: Targeting Breathing Limitations to Improve Functional Outcomes in HFpEF
Official title: Targeting Breathing Limitations to Improve Functional Outcomes in Heart Failure With Preserved Ejection Fraction (HFpEF)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure With Preserved Ejection Fraction
Obesity
Keywords: exertional dyspnea
exercise intolerance
HFpEF
breathing limitations
cardiopulmonary physiology
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2023-02-13
Enrollment: 78
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Mechanistic Clinical Trial
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: O2 cost of breathing (Objective 1)
timeFrame: Day 2
measure: Change in DOE during HeO2 breathing (Objective 2)
timeFrame: Day 3 or 4
measure: Change in peak exercise capacity during HeO2 breathing (Objective 2)
timeFrame: Day 3 or 4
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Tony G Babb, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: UT Southwestern Medical Center
name: Bryce N Balmain, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: