Femoral Artery Blood Flow During Rest and One-leg Knee Extensor Exercise in Patients With COPD (COPD-DOPPLER)

Doppler ultrasound is generally considered to provide reliable femoral blood flow measurements between rest and exercise, and the blood flow response to exercise is widely believed to be reduced in patients with chronic obstructive pulmonary disease (COPD). However, the test-retest reliability of the method during one-leg knee extensor exercise has not previously been compared between matched healthy individuals.

Study Overview

• Status: Completed
• Conditions: Healthy; Chronic Obstructive Pulmonary Disease; COPD
• Intervention / Treatment: Diagnostic test: One-legged knee-extensor exercise with Doppler measurements

Detailed Description

Experimental assessments of changes in skeletal muscle blood flow during exercise in humans are important for elucidating the factors that limit exercise capacity and adaptations, both in healthy humans, including athletes, as well as in various disease states with functional impairment, such as chronic obstructive pulmonary disease COPD). A classical 'gold standard' for measuring blood flow is thermodilution, and this has notably applied to provide data on femoral blood flow during exercise. Because thermodilution required invasive catheterization, many have replaced it with Doppler ultrasound, but the test-retest reliability of Doppler ultrasound in this context is unknown. However, many studies have used Doppler ultrasound to document that the femoral blood flow response to exercise is impaired in COPD, which ultimately affects oxygen uptake and thus exercise capacity, but the interpretation of these findings is currently hampered by the lack of knowledge regarding the test-retest reliability of the method in this patient group.

The investigators aim is to compare the femoral blood flow response to one-legged knee extensor exercise in patients with COPD vs. healthy participants, and to provide an estimate of the test-retest reliability the femoral blood flow measurements obtained by Doppler ultrasound.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • København Ø
    • Copenhagen, København Ø, Denmark, 2100
      • Center for Aktiv Sundhed (CFAS), Rigshospitalet, Copenhagen, Denmark.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for COPD patients:

• Men and women
• 45-80 years
• COPD (GOLD stage I to III)
• Forced expiratory volume in 1 sec (FEV1)/forced vital capacity ratio (FVC) < 0.8, FEV1 < 90% of predicted value
• Modified Medical Research Council score (mMRC 0 - 3) Resting arterial oxygenation > 90%

Exclusion Criteria for COPD patients:

• Symptoms of ischaemic heart disease
• Known heart failure
• Claudication
• Symptoms of disease within 2 weeks prior to the study
• Participation in pulmonary rehabilitation within 6 months
• Known malignant disease
• Pregnancy
• Unstable cardiac arrhythmic disease
• Renal or liver dysfunction

Inclusion Criteria for healthy matched controls:

• Men and women
• 45-80 years
• Normal FEV1, FVC, FEV1/FVC, and single-breath diffusion capacity
• Same sex, age (± 3 years) as the COPD patients

Exclusion Criteria for healthy matched controls:

• Known chronic lung disease
• Known ischaemic heart disease
• Known heart failure
• Symptoms of disease within 2 weeks prior to the study
• Known malignant disease
• Claudication
• Pregnancy
• Unstable cardiac arrhythmic disease
• Renal or liver dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: COPD-patients; The participants will be instructed to abstain from caffeine, nicotine, alcohol, and strenuous exercise all known to affect blood flow to the limb for 12 hours prior to the study day. After being placed on the one-leg kicking chair, baseline measurements will be performed, followed by passive leg movement for 2 minutes. Then participants will perform one-legged knee-extension exercise at submaximal intensity, first at 10% and then at 20% of the previously measured WLpeak, remaining 3.5 minutes at each level, while femoral blood flow is measured. This study day will be repeated within 2-10 days.	Diagnostic test: One-legged knee-extensor exercise with Doppler measurements; Doppler ultrasound is used while participants exercise according to the one-legged knee-extensor exercise model
Experimental: Matched healthy volunteers; The participants will be instructed to abstain from caffeine, nicotine, alcohol, and strenuous exercise all known to affect blood flow to the limb for 12 hours prior to the study day. After being placed on the one-leg kicking chair, baseline measurements will be performed, followed by passive leg movement for 2 minutes. Then participants will perform one-legged knee-extension exercise at submaximal intensity, first at 10% and then at 20% of the previously measured WLpeak, remaining 3.5 minutes at each level, while femoral blood flow is measured. This study day will be repeated within 2-10 days.	Diagnostic test: One-legged knee-extensor exercise with Doppler measurements; Doppler ultrasound is used while participants exercise according to the one-legged knee-extensor exercise model

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Between-day smallest real difference (SRD) for femoral blood flow at rest and at each relative exercise intensity in COPD vs. healthy controls	Doppler ultrasound measured blood flow during one leg knee extensor exercise with different intensities.	Measured at day 1 and day 2
• Between-day coefficient of variance (CV) for femoral blood flow at rest and at each relative exercise intensity in COPD vs. healthy controls (co-primary)	Doppler ultrasound measured blood flow during one leg knee extensor exercise with different intensities.	Measured at day 1 and day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Femoral blood flow response to exercise at each relative exercise intensity in COPD vs. healthy controls (key secondary)	Doppler ultrasound measured blood flow during one leg knee extensor exercise with different intensities.	Measured at day 1 and day 2
Between-day smallest real difference (SRD) for femoral blood flow at rest and at each absolute exercise intensity in COPD vs. healthy controls	Doppler ultrasound measured blood flow during one leg knee extensor exercise with different intensities.	Measured at day 1 and day 2
• Between-day coefficient of variance (CV) for femoral blood flow at rest and at each absolute exercise intensity in COPD vs. healthy controls (co-primary)	Doppler ultrasound measured blood flow during one leg knee extensor exercise with different intensities.	Measured at day 1 and day 2

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2023
• Primary Completion (Actual): January 12, 2024
• Study Completion (Actual): January 12, 2024

Study Registration Dates

• First Submitted: November 12, 2023
• First Submitted That Met QC Criteria: November 12, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Ultrasound; COPD; Test-retest
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: H-23049997

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Can be retrieved upon request from primary investigator.

Drug and device information, study documents

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