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Impact of Muscle Afferent Feedback During Exercise in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Not Applicable
Completed
Conditions
Chronic Obstructive Pulmonary Disease
Interventions
Drug: Placebo comparator
Registration Number
NCT01522729
Lead Sponsor
Laval University
Brief Summary

Recently, direct evidences point to the contributing role of peripheral muscle fatigue in exercise tolerance among patients with COPD. However, the physiological mechanisms by which peripheral muscle fatigue impairs exercise tolerance are still unknown, as factors regulating peripheral muscle fatigue in COPD may be complex. One possible link between limb muscle fatigue and exercise intolerance could be enhanced afferent signals from the active limb muscles to the central command, thereby limiting central motor output and eventually leading to exercise termination.

A direct method to investigate the regulation of peripheral muscle fatigue during exercise in patients with COPD is the blockade of peripheral neural afferents via lumbar anesthesia. Consequently, investigating the interplay between the peripheral muscular component and the central motor command during self-paced exercise could shed light on the regulation of peripheral muscle fatigue in COPD and its implication in exercise intolerance.

Detailed Description

The aim of the study is to characterize the role of peripheral muscle afferents on the development of muscle fatigue, cardiorespiratory response and exercise tolerance to constant-workrate endurance cycling exercise in patients with COPD.

In a double-blind randomized design, patients with GOLD stage II-III COPD will be recruited and will complete a constant-workrate cycling test following either the injection of a placebo \[NaCl, interspinous L2-L3\] or an opioid \[Fentanyl 25 µg, intrathecal L2-L3\] inhibiting central feedback of peripheral muscles sensory afferents. Quadriceps force (TwQ) will be measured by magnetic stimulation of the femoral nerve and central chemoreceptors response will be assessed by CO2 rebreathing, both performed before and after the injection. Finally, TwQ will also be measured after the endurance cycling test to assess the magnitude of quadriceps fatigue induced by symptom-limited exercise.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
8
Inclusion Criteria
  • Smoking history > 15 pack-years
  • COPD GOLD II-III (30 % predicted < FEV1 < 80 % predicted; FEV1/FVC < 0.70)
Exclusion Criteria
  • Unstable condition
  • Recent exacerbation (<3 months)
  • Recent cancer (<3 months)
  • Myopathy, neuromuscular disease
  • Unstable cardiac disease
  • Hepatic, kidney, intestinal disease
  • BMI > 35
  • PaCO2 > 45 mmHg
  • PaO2 < 60 mmHg

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo comparator-
FentanylFentanyl-
Primary Outcome Measures
NameTimeMethod
Endurance time60-min post-anesthesia - From the start to the end of the constant-workload cycling test (limited by symptoms of the patients)

Exercise tolerance is referred as the endurance time (sec) during constant-workrate cycling test at 80 % of the predetermined maximal workload in every conditions (placebo and fentanyl)

Secondary Outcome Measures
NameTimeMethod
Ventilatory response60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients)

The ventilatory response (Ventilation, L/min) will be monitored continuously during the cycling test and will be compared between the two conditions (placebo vs. fentanyl)

Quadriceps muscle fatigue15-min after the end of constant-workload cycling test

The quadriceps muscle fatigue will be monitored before and after the cycling test to quantify the extent of muscle fatigue produced by the cycling test. This will be done by magnetic stimulation of the femoral nerve and maximal voluntary contraction. Also, non-invasive surface electromyography (EMG) of the quadriceps will help to better characterize muscle fatigue.

Dynamic hyperinflation60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients) - Every 2-min during exercise

Dynamic hyperinflation will be monitored periodically every 2-min during the cycling test by manoeuvres of inspiratory capacity and will be compared between the two conditions (placebo vs. fentanyl)

Effort perception60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients) - Every 2-min during exercise

Leg fatigue and dyspnea perception (Borg scale scores) will be monitored periodically every 2-min during the cycling test and will be compared between the two conditions (placebo vs. fentanyl)

Trial Locations

Locations (1)

Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval

🇨🇦

Québec, Quebec, Canada

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