The Acute Cardiorespiratory Response to Blood-flow Restricted Versus Traditional Exercise Training Regimens (CaRe BFR) (CaRe-BFR)

The Acute Cardiorespiratory Response to Blood-flow Restricted Versus Traditional Exercise Training Regimens (CaRe BFR):4 Randomized Crossover Studies

The investigators hypothesize that BFR exercise regimens result in a different acute cardiorespiratory response pattern compared to traditional exercise regimens. Furthermore, the investigators hypothesize that these patterns differ between healthy participants and participants with COPD.

Regarding secondary objective, the investigators hypothesize that BFR results in lower blood pressure responses compared to traditional exercise training in both healthy and COPD participants.

Study Overview

• Status: Recruiting
• Conditions: COPD
• Intervention / Treatment: Other: BFR-CYC 3x2min; Other: BFR Resistance 80% LOP; Other: BFR-CYC 50% peak / 50% AOP (exhaustive); Other: BFR REsistance 48% vs. 80% LOP

Detailed Description

Detailed Description

This study investigates the acute physiological and perceptual responses to blood flow restriction (BFR) exercise compared with conventional endurance and resistance exercise in both patients with chronic obstructive pulmonary disease (COPD) and healthy individuals. The study consists of multiple experimental arms using randomized crossover designs to enable within-subject comparisons across exercise modalities and conditions.

Endurance Exercise - COPD Participants (Exhaustive Protocol)

Patients with COPD will complete three cycling exercise conditions in a randomized, crossover design:

Blood Flow Restriction Cycling (BFR-CYC)

Continuous Cycling (CONT-CYC)

Interval Cycling (INT-CYC)

All sessions will be performed on a cycle ergometer under standardized laboratory conditions, including a warm-up followed by the respective protocol. Exercise will be performed to symptom limitation (volitional exhaustion) unless predefined safety criteria are reached.

BFR-CYC: Continuous cycling at 50% peak work rate (PWR) with bilateral thigh cuffs inflated to 50% limb occlusion pressure (LOP). A maximum duration of 30 minutes is applied as a safety limit.

CONT-CYC: Continuous cycling at 65% PWR until symptom limitation.

INT-CYC: Interval cycling with repeated bouts at 80% PWR, interspersed with recovery periods at 50% PWR, until symptom limitation.

During all sessions, cardiorespiratory parameters (ventilation, oxygen uptake, carbon dioxide production), muscle oxygenation (NIRS), blood lactate, hemodynamic responses, and perceptual responses (dyspnea, perceived exertion) will be continuously measured.

Endurance Exercise - COPD and Healthy Participants (Fixed-Duration Protocol)

Both COPD patients and healthy participants will complete two endurance exercise conditions in a randomized, crossover design:

Blood Flow Restriction Cycling (BFR-CYC)

Non-BFR Control Cycling

All sessions will be conducted under standardized laboratory conditions on a cycle ergometer. Exercise will follow a fixed-duration protocol and will not be performed to volitional exhaustion, unless predefined safety criteria require early termination.

BFR-CYC: Three intervals of 2 minutes at 50% PWR, separated by 1-minute recovery periods, with bilateral thigh cuffs inflated to 50% LOP during exercise intervals.

Control: Time- and structure-matched protocol (3 × 2 minutes) without blood flow restriction at 65% PWR, with identical recovery periods.

During all sessions, cardiorespiratory, hemodynamic, and perceptual responses (dyspnea, perceived exertion) will be continuously measured.

Resistance Exercise - COPD and Healthy Participants (BFR vs Control, Fixed Protocol)

Both COPD patients and healthy participants will complete two resistance exercise conditions in a randomized, crossover design:

Blood Flow Restriction Resistance Exercise (BFR-RE)

Non-BFR Control Resistance Exercise

All sessions will be performed on a leg press device under standardized laboratory conditions. Exercise will follow a fixed set and repetition scheme and will not be performed to volitional exhaustion, unless predefined safety criteria require early termination.

BFR-RE: Unilateral right-leg press at 40% of one-repetition maximum (1RM) with cuffs inflated to 80% LOP. Protocol: 4 sets (30-15-15-15 repetitions).

Control: Bilateral leg press at 40% 1RM, 3 sets of 15 repetitions, without blood flow restriction.

During all sessions, cardiorespiratory, hemodynamic, and perceptual responses will be continuously measured.

Resistance Exercise - Healthy Participants (LOP Comparison Arm)

Healthy participants will complete two BFR resistance exercise conditions in a randomized, crossover design:

BFR at 40% LOP

BFR at 80% LOP

All sessions will be conducted on a leg press device under standardized laboratory conditions. Pneumatic cuffs will be applied to the proximal thigh of the right leg.

Participants will perform unilateral right-leg press exercise at 40% 1RM using a standardized protocol of 4 sets (30-15-15-15 repetitions) with fixed rest intervals. The protocol will be completed as prescribed (not to volitional exhaustion) unless predefined safety criteria require early termination.

Neuromuscular function will be assessed using maximal voluntary contraction (MVC) of the knee extensors measured before and immediately after exercise. Voluntary activation will be evaluated using the twitch interpolation technique with supramaximal electrical stimulation.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christan Clarenbach, Dr. med; Phone Number: 044 255 22 21; Email: Christian.clarenbach@usz.ch
• Study Contact Backup: Name: Manuel Kuhn, PhD Student; Phone Number: 0798526722; Email: manuel.kuhn@usz.ch

Study Locations

• Switzerland
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8091
      • Recruiting
      • University Hospital Zurich
      • Contact: Manuel Kuhn, MSc; Phone Number: 0432532681; Email: manuel.kuhn@usz.ch
      • Contact: Alexandra Arvaji; Phone Number: 0432530131; Email: alexandra.arvaji@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion and exclusion for the healthy participants are defined by the following criteria.

Inclusion criteria:

• Age ≥ 18 years
• Clinically healthy

Exclusion criteria:

• Physical or intellectual impairment precluding informed consent or protocol adherence
• Non-German speaking (precluding informed consent)
• Pain during exercise of any origin
• Pregnancy
• History of thromboembolic event in the lower extremity
• Resting systolic blood pressure <100 mmHg

Inclusion and exclusion for the COPD participants are defined by the following criteria.

Inclusion criteria:

• Age ≥ 18 years
• Diagnosed COPD according to GOLD-guidelines12

Exclusion criteria:

• Physical or intellectual impairment precluding informed consent or protocol adherence
• Non-German speaking (precluding informed consent)
• Acute or recent (within the last 6 weeks) exacerbation of COPD
• Pain during exercise of any origin
• Pregnancy
• History of thromboembolic event in the lower extremity
• Resting systolic blood pressure <100 mmHg

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endurance Exercise - COPD and Healthy Participants (Fixed-Duration Protocol); Both COPD patients and healthy participants will complete two endurance exercise conditions in a randomized, crossover design: Blood Flow Restriction Cycling (BFR-CYC); Non-BFR Control Cycling BFR-CYC: Three intervals of 2 minutes at 50% PWR, separated by 1-minute recovery periods, with bilateral thigh cuffs inflated to 50% LOP during exercise intervals. Control: Time- and structure-matched protocol (3 × 2 minutes) without blood flow restriction at 65% PWR, with identical recovery periods.	Other: BFR-CYC 3x2min; BFR-CYC: Three intervals of 2 minutes at 50% PWR, separated by 1-minute recovery periods, with bilateral thigh cuffs inflated to 50% LOP during exercise intervals.
Experimental: Resistance Exercise - COPD and Healthy Participants (BFR vs Control, Fixed Protocol); Both COPD patients and healthy participants will complete two resistance exercise conditions in a randomized, crossover design: Blood Flow Restriction Resistance Exercise (BFR-RE); Non-BFR Control Resistance Exercise BFR-RE: Unilateral right-leg press at 40% of one-repetition maximum (1RM) with cuffs inflated to 80% LOP. Protocol: 4 sets (30-15-15-15 repetitions). Control: Bilateral leg press at 40% 1RM, 3 sets of 15 repetitions, without blood flow restriction.	Other: BFR Resistance 80% LOP; BFR-RE: Unilateral right-leg press at 40% of one-repetition maximum (1RM) with cuffs inflated to 80% LOP. Protocol: 4 sets (30-15-15-15 repetitions).
Experimental: Endurance Exercise - COPD Participants (Exhaustive Protocol); Patients with COPD will complete three cycling exercise conditions in a randomized, crossover design: Blood Flow Restriction Cycling (BFR-CYC); Continuous Cycling (CONT-CYC); Interval Cycling (INT-CYC)	Other: BFR-CYC 50% peak / 50% AOP (exhaustive); BFR-CYC: Continuous cycling at 50% peak work rate (PWR) with bilateral thigh cuffs inflated to 50% limb occlusion pressure (LOP). A maximum duration of 30 minutes is applied as a safety limit.
Experimental: Resistance Exercise - Healthy Participants (LOP Comparison Arm); Healthy participants will complete two BFR resistance exercise conditions in a randomized, crossover design: BFR at 40% LOP; BFR at 80% LOP Participants will perform unilateral right-leg press exercise at 40% 1RM using a standardized protocol of 4 sets (30-15-15-15 repetitions) with fixed rest intervals. The protocol will be completed as prescribed (not to volitional exhaustion) unless predefined safety criteria require early termination.	Other: BFR REsistance 48% vs. 80% LOP; BFR at 40% LOP; BFR at 80% LOP All sessions will be conducted on a leg press device under standardized laboratory conditions. Pneumatic cuffs will be applied to the proximal thigh of the right leg. Participants will perform unilateral right-leg press exercise at 40% 1RM using a standardized protocol of 4 sets (30-15-15-15 repetitions) with fixed rest intervals. The protocol will be completed as prescribed (not to volitional exhaustion) unless predefined safety criteria require early termination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endurance Exercise:(Fixed-Duration Protocol):	Minute ventilation (VE) will be continuously assessed during cycling exercise across all conditions to evaluate ventilatory demand.	Continuously during exercise and at end of exercise, with recovery measurements obtained within 4 minutes post-exercise
Resistance Exercise - Healthy Participants (LOP Comparison Arm): Within-subject difference change in Maximal Voluntary Contraction (MVC)	Maximal voluntary contraction (MVC) of the knee extensors will be assessed before and immediately after unilateral leg press exercise performed with blood flow restriction at 40% and 80% limb occlusion pressure (LOP). MVC will be measured using an isometric setup, and voluntary activation will be evaluated using the twitch interpolation technique with supramaximal electrical stimulation. The primary outcome is the change in MVC from pre- to post-exercise, reflecting exercise-induced neuromuscular fatigue.	Pre-exercise and immediately post-exercise (within minutes after completion of the exercise protocol)
Endurance Exercise - COPD Participants (Exhaustive Protocol): Within-subject difference in maximal minute ventilation (VE) between BFR and traditional exercise regimens	Minute ventilation (VE) will be continuously assessed during cycling exercise across all conditions to evaluate ventilatory demand and response.	Continuously during exercise, at end of exercise (peak value), and within 4 minutes post-exercise
Resistance Exercise:(Healthy and COPD): Ventilatory Response (Ventilation, VE)	Minute ventilation (VE) will be continuously assessed during cycling exercise across all conditions to evaluate ventilatory demand.	Continuously during exercise and at end of exercise, with recovery measurements obtained within 4 minutes post-exercise

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resistance Exercise - Healthy Participants (LOP Comparison Arm): Muscle Oxygenation (NIRS)	Muscle oxygenation of the knee extensors will be continuously assessed using near-infrared spectroscopy (NIRS) during unilateral leg press exercise performed with blood flow restriction at 40% and 80% limb occlusion pressure (LOP). Parameters such as tissue oxygen saturation will be analyzed to evaluate local muscular oxygenation responses.	Continuously during exercise and immediately post-exercise
Resistance Exercise - Healthy Participants (LOP Comparison Arm): Perceived Exertion / Dyspnea (Borg Scale)	Perceived exertion will be assessed using the Borg rating of perceived exertion (RPE) scale during cycling exercise. Perceived breathlessness will be assessed using the Borg dyspnea scale during exercise.	At baseline (pre-exercise), after each set, immediately post-exercise, and at 2 and 4 minutes post-exercise
Endurance Exercise - COPD Participants (Exhaustive Protocol): Cardiorespiratory Response (Vo2 , VCO2)	Oxygen uptake (VO₂) will be continuously measured during cycling exercise performed under three conditions (BFR-CYC, CONT-CYC, INT-CYC) to symptom limitation. The primary outcome will be the peak VO₂ achieved at end of exercise, reflecting maximal cardiorespiratory response. Carbon dioxide production (VCO₂) will be continuously measured during exercise to assess metabolic and ventilatory responses.	Continuously during exercise and at end of exercise, with recovery measurements obtained within 4 minutes post-exercise
Endurance Exercise - COPD Participants (Exhaustive Protocol):NIRS	Muscle oxygenation will be assessed using near-infrared spectroscopy (NIRS) during cycling exercise to evaluate local muscular oxygenation under BFR and non-BFR conditions.	Continuously during exercise and at end of exercise, with recovery measurements obtained within 4 minutes post-exercise
Endurance Exercise - COPD Participants (Exhaustive Protocol): Blood Lactate Concentration	Capillary blood lactate concentration will be measured to assess metabolic stress induced by the different exercise conditions.	At baseline (pre-exercise) at peak and 3 min wpost-exercise
Endurance Exercise - COPD Participants (Exhaustive Protocol): Perceived Exertion and Dyspnea (Borg Scale)	Perceived exertion will be assessed using the Borg rating of perceived exertion (RPE) scale during cycling exercise. Perceived breathlessness will be assessed using the Borg dyspnea scale during exercise.	At baseline (pre-exercise), during exercise (at regular intervals), at end of exercise, and within 4 minutes post-exercise
Endurance Exercise - COPD Participants (Exhaustive Protocol): Exercise Tolerance (Time to Exhaustion)	Exercise tolerance will be defined as the time from the start of exercise to symptom limitation (volitional exhaustion).	During exercise (recorded at end of exercise)
Endurance Exercise:(Fixed-Duration Protocol): Cardiorespiratory Response (Vo2 , VCO2)	Carbon dioxide production (VCO₂) will be continuously measured during exercise to assess metabolic and ventilatory responses Oxygen uptake (VO₂) will be continuously measured during cycling exercise performed under two conditions. The primary outcome will be the peak VO₂ achieved at end of exercise, reflecting maximal cardiorespiratory response.	Continuously during exercise and at end of exercise, with recovery measurements obtained within 4 minutes post-exercise
Endurance Exercise:(Fixed-Duration Protocol): Borg Scale (Dyspnea/Perceived Exertion)	Perceived exertion will be assessed using the Borg rating of perceived exertion (RPE) scale during cycling exercise. Perceived breathlessness will be assessed using the Borg dyspnea scale during exercise.	At baseline (pre-exercise), during exercise (at regular intervals), at end of exercise, and within 4 minutes post-exercise
Resistance Exercise:(Healthy and COPD): Cardiorespiratory Response	Oxygen uptake (VO₂) will be continuously measured during cycling exercise performed under two conditions. Carbon dioxide production (VCO₂) will be continuously measured during exercise to assess metabolic and ventilatory responses.	Continuously during exercise and at end of exercise, with recovery measurements obtained within 4 minutes post-exercise
Resistance Exercise:(Healthy and COPD): Dyspnea (Borg Scale/ Perceived Exertion )	Perceived exertion will be assessed using the Borg rating of perceived exertion (RPE) scale during cycling exercise. Perceived breathlessness will be assessed using the Borg dyspnea scale during exercise.	At baseline (pre-exercise), during exercise (at regular intervals), at end of exercise, and within 4 minutes post-exercise

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Christian Clarenbach, Dr. med, University of Zurich

Publications and helpful links

General Publications

• Kuhn M, Clarenbach CF, Klay A, Kohler M, Mayer LC, Luchinger M, Andrist B, Radtke T, Haile SR, Sievi NA, Kohlbrenner D. Exploring immediate cardiorespiratory responses: low-intensity blood flow restricted cycling vs. moderate-intensity traditional exercise in a randomized crossover trial. BMC Sports Sci Med Rehabil. 2024 Aug 15;16(1):172. doi: 10.1186/s13102-024-00951-0.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: December 17, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 2021-02038

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