Neuromuscular Fatigue During Exercise in COPD-HF Overlap

NCT05235685 | Recruiting DMC

• 1 other identifier: 2021-A02359-32
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale. Chronic obstructive pulmonary disease (COPD) and heart failure (HF) coexist in approximately one third of patients presenting with one of these conditions. From a clinical standpoint, impaired tissue oxygen (O2) delivery stands as a common pathological mechanism of these cardiorespiratory diseases. Recent evidence suggest that muscle and cerebral blood flow and oxygenation are further impaired during exercise in patients with COPD-HF overlap compared to isolated diseases. However, it remains unknown whether impaired O2 delivery is associated with exaggerated manifestations of peripheral and central fatigue in COPD-HF overlap. In addition, improving cardiopulmonary interactions through non invasive positive pressure ventilation or through the addition of a hyperoxic gas mixture during exercise have been associated with enhanced cerebral and muscle O2 delivery and oxygenation in patients with COPD or HF. It is, therefore, conceivable that improved O2 delivery to these structures have beneficial influence on exercise capacity in patients with COPD-HF overlap due to less peripheral and central fatigue. Aims. To investigate the influence of impaired O2 delivery during exercise, and its alleviation with different interventions (non invasive positive pressure ventilation or hyperoxia), on neuromuscular fatigue in patients with COPD-HF.

Conditions

Pulmonary Disease, Chronic Obstructive; Heart Failure

Keywords

Exercise Tolerance; Hypoxia, Brain; Muscle Fatigue; Oxygen; Spectroscopy, Near-Infrared; Ultrasonography, Doppler, Transcranial

Outcome Measures

Primary Outcomes (1)

• Muscle fatigue

  Muscle fatigue assessed by magnetic stimulation of the femoral nerve

  Muscle fatigue assessed immediately after exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trial in COPD-HF) comparisons

Secondary Outcomes (4)

• Exertional symptoms

  Symptoms during exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trial in COPD-HF) comparisons

• Tissue oxygenation

  Tissue oxygenation during exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trial in COPD-HF) comparisons

• Cerebral blood flow

  Cerebral blood flow during exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trial in COPD-HF) comparisons

• Cardiac output

  Cardiac output during exercise, between-group (COPD vs COPD-HF under medical air) and within-group (medical air vs intervention trial in COPD-HF) comparisons

Study Arms (2)

Patients with COPD

ACTIVE COMPARATOR

Patients with COPD will only exercise under medical air (for between-group comparison: COPD vs COPD-HF)

Other: Medical air

Patients with COPD-HF overlap

EXPERIMENTAL

Patients with COPD-HF overlap will first exercise under medical air (for between-group comparison: COPD vs COPD-HF); Patients with COPD-HF overlap will then exercise under intervention (hyperoxia, for within-group comparison: medical air vs intervention trial)

Other: Medical air; Other: Hyperoxia

Interventions

Medical air OTHER

Exercise under medical air, both arms exposed.

Patients with COPD; Patients with COPD-HF overlap

Hyperoxia OTHER

Exercise under hyperoxia, only experimental arm exposed.

Patients with COPD-HF overlap

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years;
• COPD: mild-to-severe airflow obstruction (forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio \<0.70; post-bronchodilator FEV1 \> 30% predicted);
• HF: reduced left ventricular ejection fraction (\<50%, for COPD-HF patients only);
• HF: New York Heart Association Functional Classification I to III (for COPD-HF patients only);
• Clinical stability for both diseases (COPD and/or HF) and no recent (within 3 months) exacerbation requiring a change in medications;
• Patient benefiting from health care coverage;
• Patient able to provide written informed consent.

You may not qualify if:

• Inability to perform cycle ergometry;
• Medical device incompatible with magnetic stimulation;
• Counter-indication to perform exercise test;
• Patient refusing to sign written informed consent;
• Patient not benefiting from health care coverage;
• Patient exceeding the annual ceiling of authorized compensation received following participation to a clinical trial;
• Patient deprived of freedom by judicial or administrative decision;
• Patient subject to a measure of legal protection (safeguard of justice, guardianship, curatorship), who cannot be included in clinical trials;
• Pregnant or nursing woman.

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

CHU Grenoble Alpes - Hopital Sud (Laboratoire HP2)

Échirolles, Auvergne-Rhône-Alpes, 38130, France

RECRUITING

Related Publications (7)

• Rutten FH, Cramer MJ, Grobbee DE, Sachs AP, Kirkels JH, Lammers JW, Hoes AW. Unrecognized heart failure in elderly patients with stable chronic obstructive pulmonary disease. Eur Heart J. 2005 Sep;26(18):1887-94. doi: 10.1093/eurheartj/ehi291. Epub 2005 Apr 28.

  PMID: 15860516 BACKGROUND

• Oliveira MF, Zelt JT, Jones JH, Hirai DM, O'Donnell DE, Verges S, Neder JA. Does impaired O2 delivery during exercise accentuate central and peripheral fatigue in patients with coexistent COPD-CHF? Front Physiol. 2015 Jan 7;5:514. doi: 10.3389/fphys.2014.00514. eCollection 2014.

  PMID: 25610401 BACKGROUND

• Oliveira MF, Alencar MC, Arbex F, Souza A, Sperandio P, Medina L, Medeiros WM, Hirai DM, O'Donnell DE, Neder JA. Effects of heart failure on cerebral blood flow in COPD: Rest and exercise. Respir Physiol Neurobiol. 2016 Jan 15;221:41-8. doi: 10.1016/j.resp.2015.10.005. Epub 2015 Oct 31.

  PMID: 26528895 BACKGROUND

• Oliveira MF, Arbex FF, Alencar MC, Souza A, Sperandio PA, Medeiros WM, Mazzuco A, Borghi-Silva A, Medina LA, Santos R, Hirai DM, Mancuso F, Almeida D, O'Donnell DE, Neder JA. Heart Failure Impairs Muscle Blood Flow and Endurance Exercise Tolerance in COPD. COPD. 2016 Aug;13(4):407-15. doi: 10.3109/15412555.2015.1117435. Epub 2016 Jan 20.

  PMID: 26790095 BACKGROUND

• Borghi-Silva A, Oliveira CC, Carrascosa C, Maia J, Berton DC, Queiroga F Jr, Ferreira EM, Almeida DR, Nery LE, Neder JA. Respiratory muscle unloading improves leg muscle oxygenation during exercise in patients with COPD. Thorax. 2008 Oct;63(10):910-5. doi: 10.1136/thx.2007.090167. Epub 2008 May 20.

  PMID: 18492743 BACKGROUND

• Borghi-Silva A, Carrascosa C, Oliveira CC, Barroco AC, Berton DC, Vilaca D, Lira-Filho EB, Ribeiro D, Nery LE, Neder JA. Effects of respiratory muscle unloading on leg muscle oxygenation and blood volume during high-intensity exercise in chronic heart failure. Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2465-72. doi: 10.1152/ajpheart.91520.2007. Epub 2008 Mar 28.

  PMID: 18375714 BACKGROUND

• Oliveira MF, Rodrigues MK, Treptow E, Cunha TM, Ferreira EM, Neder JA. Effects of oxygen supplementation on cerebral oxygenation during exercise in chronic obstructive pulmonary disease patients not entitled to long-term oxygen therapy. Clin Physiol Funct Imaging. 2012 Jan;32(1):52-8. doi: 10.1111/j.1475-097X.2011.01054.x. Epub 2011 Oct 3.

  PMID: 22152079 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Heart Failure; Hypoxia, Brain

Interventions

Air

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment and Public Health

Study Officials

• Stéphane Doutreleau, MD, PhD

  CHU Grenoble Alpes, Grenoble Alpes University

  PRINCIPAL INVESTIGATOR

• Mathieu Marillier, PhD

  CHU Grenoble Alpes, Grenoble Alpes University

  STUDY CHAIR

Central Study Contacts

Stéphane Doutreleau, MD, PhD

CONTACT

+33476767773; sdoutreleau@chu-grenoble.fr

Mathieu Marillier, PhD

CONTACT

+33681552231; mmarillier@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients masked from intervention (gas mixture being delivered). Non-randomized (air medical condition tested first).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2 parralel study groups: patients with COPD (N=20); patients with COPD-HF overlap (N=20) Between-group comparison (COPD vs COPD-HF) under medical air Only patients with COPD-HF overlap exposed to intervention (hyperoxia)

Study Record Dates

• First Submitted: January 18, 2022
• First Posted: February 11, 2022
• Study Start: February 21, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: June 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available on reasonable request to the Investigators (unidentified patients' data) upon study completion and for an unrestricted period of time.
• Access Criteria: Data available on reasonable request to the Investigators.

Locations

FR (1)