Effects of Long Acting Bronchodilators on CARDiac Autonomic Control in Chronic Obstructive Pulmonary Disease (COPD)

The aim of this interventional, randomized, double-blind, monocentric, cross-over study is to quantify the possible deleterious effect on the cardiac autonomic nervous system control of two long-acting anticholinergic bronchodilatators (tiotropium and glycopyrronium) and one beta-2 agonist long-acting bronchodilatator (indacaterol ) in patients with mild COPD.

This is a cross-over study with randomization in terms of 4 treatments: two long-acting muscarinic antagonists (tiotropium and glycopyrronium), one long-acting beta-adrenoceptor agonist(indacaterol) and placebo. Each subject will pass 4 experimental random sessions, separated by at least 48 hours given the pharmacokinetic properties of the drugs tested. During each of the 4 sessions, blood pressure will be measured. Drugs inhaled by the patient will be prepared and administered by the nurse according to the randomization schedule. Patients and investigators will be blinded regarding the administered drug/placebo (anonymized inhaler). After 15 minutes (at rest, at neutral temperature), patients will have continuous measurement of blood pressure and heart rate (by a sphygmomanometer) (1) in supine position and (2) after a passive tilt test on a tilt test table. A flow-volume loop (BDV) will be performed after the tilt table test (measurement of Forced expiratory volume in 1 second (FEV1) and FVC).