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

Laval University

Status: Completed

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: Fentanyl; Drug: Placebo comparator

Study type: Interventional

Funder types: Other

Identifiers

NCT01522729

SPINAL-20520

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: Male

Ages: 55 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

8 participants in 2 patient groups

Fentanyl

Experimental group

Treatment:

Drug: Fentanyl

Placebo

Experimental group

Treatment:

Drug: Placebo comparator