Clinical trial NCT01522729: Impact of Muscle Afferent Feedback During Exercise in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: Impact of Somatosensory Feedback on Peripheral Muscle Fatigue and Exercise Tolerance in Patients With COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: Chronic pulmonary obstructive disease
Muscle dysfunction
Exercise intolerance
Muscle afferents
Ventilation
Lead sponsor: Laval University
Sponsor class: OTHER
First posted: 2012-02-01
Enrollment: 8
Sex: MALE
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Endurance time
timeFrame: 60-min post-anesthesia - From the start to the end of the constant-workload cycling test (limited by symptoms of the patients)
Secondary outcomes:
measure: Ventilatory response
timeFrame: 60-min post-anesthesia-From the start to the end of the constant-workload cycling test (limited by symptoms of the patients)
measure: Quadriceps muscle fatigue
timeFrame: 15-min after the end of constant-workload cycling test
measure: Dynamic hyperinflation
timeFrame: 60-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
measure: Effort perception
timeFrame: 60-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
Other outcomes:
Locations:
city: Québec
country: Canada
facility: Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
state: Quebec
Study officials:
affiliation: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
name: François Maltais, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gagnon P, Bussieres JS, Ribeiro F, Gagnon SL, Saey D, Gagne N, Provencher S, Maltais F. Influences of spinal anesthesia on exercise tolerance in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012 Oct 1;186(7):606-15. doi: 10.1164/rccm.201203-0404OC. Epub 2012 Jul 19.