Targeting Breathing Limitations to Improve Functional Outcomes in HFpEF

Targeting Breathing Limitations to Improve Functional Outcomes in Heart Failure With Preserved Ejection Fraction (HFpEF)

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Other: HeO2 gas mixture; Other: Room air gas mixture

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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Raksa B Moran, RN; Phone Number: 214-345-6574; Email: raksamoran@texashealth.org
• Study Contact Backup: Name: Jessica N Alcala, RN; Phone Number: 214-345-6574; Email: jessicaalcala@texashealth.org

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Contact: Raksa B Moran, RN; Phone Number: 214-345-6574; Email: raksamoran@texashealth.org
      • Contact: Jessica N Alcala, RN; Phone Number: 2143456574; Email: jessicaalcala@texashealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: HeO2 gas mixture; Low-density helium-oxygen gas mixture (HeO2: 21% O2 and 79% He). Participant will be breathing this gas mixture.; Other: Room air gas mixture; Normal room air
Experimental: 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.	Other: HeO2 gas mixture; Low-density helium-oxygen gas mixture (HeO2: 21% O2 and 79% He). Participant will be breathing this gas mixture.; Other: Room air gas mixture; Normal room air

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
O2 cost of breathing (Objective 1)	O2 cost of breathing measured during eucapnic voluntary hyperventilation, and calculated using oxygen uptake and ventilation variables.	Day 2
Change in DOE during HeO2 breathing (Objective 2)	Dyspnea on Exertion (DOE) will be assessed via ratings of perceived breathlessness (RPB) using a 0-10 Borg Scale, and will be compared with that measured during room air breathing.	Day 3 or 4
Change in peak exercise capacity during HeO2 breathing (Objective 2)	Peak exercise capacity will be assessed by measuring peak oxygen uptake (in L/min, measured via a breath-by-breath metabolic measurement system), peak power output recorded from a cycle ergometer (Watts), and/or total exercise duration (minutes).	Day 3 or 4

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Bryce N Balmain, Ph.D., UT Southwestern Medical Center; Principal Investigator: Tony G Babb, Ph.D., UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: February 8, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: exercise intolerance; HFpEF; exertional dyspnea; breathing limitations; cardiopulmonary physiology
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: STU-2022-1174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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