Acute Muscular and Vascular Responses to a Single Session of Exercise With BFR in COPD (2BFREE_aigu)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Disease (COPD), Chronic Obstructive; Control Condition; Blood Flow Restriction Training (BFRT)
• Intervention / Treatment: Device: Blood Flow Restriction; Device: Standard exercise session

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mathieu Marillier, PhD; Phone Number: +33681552231; Email: mmarillier@chu-grenoble.fr
• Study Contact Backup: Name: Bruno Degano, MD, PhD; Phone Number: +33664810986; Email: bdegano@chu-grenoble.fr

Study Locations

• France
  • Auvergne-Rhône-Alpes
    • La Tronche, Auvergne-Rhône-Alpes, France, 38700
      • CReSI - Laboratoire HP2
      • Contact: Mathieu Marillier, PhD; Phone Number: +33681552231; Email: mmarillier@chu-grenoble.fr
      • Contact: Bruno Degano, MD, PhD; Phone Number: +33664810986; Email: bdegano@chu-grenoble.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood flow restricted exercise session; Sub-study 1: resistance exercise session with Blood Flow Restriction (RE-BFR); Sub-study 2: aerobic endurance exercise session with Blood Flow Restriction (END-BFR).	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.
Active Comparator: Standard exercise session; Sub-study 1: resistance exercise session (RE); Sub-study 2: aerobic endurance exercise session (END).	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle fatigue	Muscle fatigue assessed by magnetic stimulation of the femoral nerve	Assessed 15-minutes before, and 3, 30, 60-minutes after exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow Mediated Dilation (FMD)	Brachial artery FMD assessed by ultrasound	30-minutes pre-exercise, and 10 and 75-minutes post-exercise
Symptoms of dyspnea	Modified Borg scale: ranging from 0 (nothing at all) to 10 (maximal)	Assessed at the end of each exercise set/bout (sub-study 1) or every 2 minutes throughout exercise (sub-study 2)
Affective valence	Feeling scale: ranging from -5 (very bad) to 5 (very good)	Assessed at the end of each exercise set/bout (sub-study 1) or every 2 minutes throughout exercise (sub-study 2)
Affective intensity	Felt Arousal Scale: ranging from 1 (low activation state) to 6 (high activation state)	Assessed at the end of each exercise set/bout (sub-study 1) or every 2 minutes throughout exercise (sub-study 2)
Oxygen uptake	Using metabolic chart, in L/min	Assessed at the end of each exercise set/bout (sub-study 1) or continuously throughout exercise (sub-study 2).
Carbon dioxide output	Using metabolic chart, in L/min	Assessed at the end of each exercise set/bout (sub-study 1) or continuously throughout exercise (sub-study 2).
Minute ventilation	Using metabolic chart, in L/min	Assessed at the end of each exercise set/bout (sub-study 1) or continuously throughout exercise (sub-study 2).
Breathing pattern	Tidal volume (in L) and respiratory rate (in breaths per minute), using metabolic chart	Assessed at the end of each exercise set/bout (sub-study 1) or continuously throughout exercise (sub-study 2).
Heart rate	Using electrocardiogram, in beats/min	Continuous monitoring throughout the exercise session.
Blood pressure	Using digital cuff system, in mmHg	Continuous monitoring throughout the exercise session.
Cardiac output	Using impedance cardiography, in L/min	Continuous monitoring throughout the exercise session.
Leg discomfort	Modified Borg scale: ranging from 0 (nothing at all) to 10 (maximal)	Assessed at the end of each exercise set/bout (sub-study 1) or every 2 minutes throughout exercise (sub-study 2)

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble

Publications and helpful links

General 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: June 11, 2026
• First Submitted That Met QC Criteria: June 19, 2026
• First Posted (Actual): June 25, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Aerobic exercise; COPD; Resistance exercise; Muscle Fatigue; Blood Flow Restriction Training
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Therapeutics; Physical Therapy Modalities; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Blood Flow Restriction Therapy
• Other Study ID Numbers: EssaiClinique_2BFREEaigu; 2026-A00501-50 (Registry Identifier: CPP Sud-Méditerranée I)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data that support the findings of this study will be made available from the contact person/backup upon reasonable request.

Drug and device information, study documents

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