Acute Muscular and Vascular Responses to a Single Session of Exercise With BFR in COPD

Official title

Blood Flow Restriction (BFR): a Novel Approach to Potentiate the Effects of Rehabilitative Exercise Training in COPD? Study of Acute - Muscular, and Vascular - Responses to a Single Session of Exercise With BFR

Overview

Exercise training is a cornerstone of pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD). However, some patients derive limited benefits from conventional exercise programs. Previous studies suggest that the magnitude of exercise-induced muscle fatigue is associated with training effectiveness, with patients unable to develop significant muscle fatigue ("non-fatiguers") showing smaller improvements in functional capacity and quality of life. Blood flow restriction (BFR) exercise consists in performing physical exercise while applying external pressure to the proximal part of the exercising limb, thereby reducing oxygen delivery to the muscles and limiting metabolite clearance. This approach has been shown to induce significant muscular adaptations despite the use of low exercise intensities. Because exercise intensity in COPD patients is often constrained by ventilatory limitations, BFR training may enhance muscle adaptations while reducing respiratory stress, potentially improving the effectiveness of PR. The primary objective of this monocentric randomized crossover study is to compare lower-limb muscle fatigue induced by a single exercise session performed with BFR versus a standard exercise session in patients with COPD.

Detailed description

Two exercise modalities commonly used in pulmonary rehabilitation will be investigated independently in two sub-studies: (1) resistance training performed with BFR or without BFR, and (2) aerobic endurance training performed with BFR or without BFR.

Interventions

• Device Blood Flow Restriction
  Sub-study 1 (RE-BFR): Resistance training consisting of 1 × 30 repetitions followed by 3 × 15 repetitions at 30% 1-RM, performed with thigh BFR to 50-60% of arterial occlusion pressure (AOP). Sub-study 2 (END-BFR): Low-intensity cycling exercise (\~30% peak aerobic power) performed with thigh BFR to 50-60% of AOP.
• Device Standard exercise session
  Sub-study 1 (RE): Resistance exercise consisting of 4 × 10 repetitions at 60-70% 1-RM. Sub-study 2 (END): Conventional aerobic endurance cycling exercise performed at \~50% peak aerobic power.

Primary outcome measures

• Muscle fatigue [Time frame: Assessed 15-minutes before, and 3, 30, 60-minutes after exercise]

Secondary outcome measures (12)

• Flow Mediated Dilation (FMD) [Time frame: 30-minutes pre-exercise, and 10 and 75-minutes post-exercise]
• Symptoms of dyspnea [Time frame: Assessed at the end of each exercise set/bout (sub-study 1) or every 2 minutes throughout exercise (sub-study 2)]
• Leg discomfort [Time frame: Assessed at the end of each exercise set/bout (sub-study 1) or every 2 minutes throughout exercise (sub-study 2)]
• Affective valence [Time frame: Assessed at the end of each exercise set/bout (sub-study 1) or every 2 minutes throughout exercise (sub-study 2)]
• Affective intensity [Time frame: Assessed at the end of each exercise set/bout (sub-study 1) or every 2 minutes throughout exercise (sub-study 2)]
• Oxygen uptake [Time frame: Assessed at the end of each exercise set/bout (sub-study 1) or continuously throughout exercise (sub-study 2).]
• Carbon dioxide output [Time frame: Assessed at the end of each exercise set/bout (sub-study 1) or continuously throughout exercise (sub-study 2).]
• Minute ventilation [Time frame: Assessed at the end of each exercise set/bout (sub-study 1) or continuously throughout exercise (sub-study 2).]
• Breathing pattern [Time frame: Assessed at the end of each exercise set/bout (sub-study 1) or continuously throughout exercise (sub-study 2).]
• Heart rate [Time frame: Continuous monitoring throughout the exercise session.]
• Blood pressure [Time frame: Continuous monitoring throughout the exercise session.]
• Cardiac output [Time frame: Continuous monitoring throughout the exercise session.]

Eligibility criteria

Inclusion criteria

• Negative pregnancy test and use of an acceptable contraceptive method throughout the study duration for women of childbearing potential
• Established COPD defined as obstructive ventilatory defect (FEV1/FVC < 0.70 or below the 5th percentile)
• Resting lung hyperinflation defined as functional residual capacity > 2.5 z-scores according to the Global Lung Function Initiative (GLI)
• Clinical stability of COPD for at least 3 months, with no recent exacerbation requiring treatment modification
• Covered by a national health insurance system
• Able and willing to provide written informed consent

Non-inclusion Criteria:

• Presence of a medical device incompatible with magnetic stimulation
• Inability to perform an exercise test on a cycle ergometer
• Any usual contraindication to exercise testing, including:

• Recent myocardial infarction (3-5 days)
• Unstable coronary insufficiency
• Severe stenotic valvular disease
• Uncontrolled arrhythmia with hemodynamic instability
• Recent unexplained syncope
• Uncontrolled heart failure
• Uncontrolled arterial hypertension (systolic blood pressure ≥200 mmHg and/or diastolic blood pressure ≥110 mmHg at rest)
• Acute thromboembolic disease and/or pulmonary edema
• Conditions contraindicating the use of blood flow restriction (BFR), including:

• Coagulation disorder
• Peripheral neuropathy
• Uncontrolled hypertension (>160/100 mmHg)
• Peripheral arterial disease
• History of venous thrombosis
• Intensive care unit stay within the last 3 months
• Participation in another study during an exclusion period
• Inability to be contacted in case of emergency
• Individuals covered under Articles L1121-5 to L1121-8 of the French Public Health Code (protected populations, including pregnant or breastfeeding women, prisoners, minors, individuals under legal protection, psychiatric inpatients, etc.)
• Staff members with a hierarchical relationship with the principal investigator

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• CReSI - Laboratoire HP2 — La Tronche

Publications

• Kilgas MA, Yoon T, McDaniel J, Phillips KC, Elmer SJ. Physiological Responses to Acute Cycling With Blood Flow Restriction. Front Physiol. 2022 Mar 11;13:800155. doi: 10.3389/fphys.2022.800155. eCollection 2022. PMID 35360241
• Burtin C, Saey D, Saglam M, Langer D, Gosselink R, Janssens W, Decramer M, Maltais F, Troosters T. Effectiveness of exercise training in patients with COPD: the role of muscle fatigue. Eur Respir J. 2012 Aug;40(2):338-44. doi: 10.1183/09031936.00111811. Epub 2011 Dec 1. PMID 22135284
• Spruit MA, Augustin IM, Vanfleteren LE, Janssen DJ, Gaffron S, Pennings HJ, Smeenk F, Pieters W, van den Bergh JJ, Michels AJ, Groenen MT, Rutten EP, Wouters EF, Franssen FM; CIRO+ Rehabilitation Network. Differential response to pulmonary rehabilitation in COPD: multidimensional profiling. Eur Respir J. 2015 Dec;46(6):1625-35. doi: 10.1183/13993003.00350-2015. Epub 2015 Oct 9. PMID 26453626
• Mador MJ, Mogri M, Patel A. Contractile fatigue of the quadriceps muscle predicts improvement in exercise performance after pulmonary rehabilitation. J Cardiopulm Rehabil Prev. 2014 Jan-Feb;34(1):54-61. doi: 10.1097/HCR.0000000000000023. PMID 24165798

Identifiers

NCT: NCT07668921 · EssaiClinique_2BFREEaigu · 2026-A00501-50

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗