Clinical trial NCT02872090: Effects of Long Acting Bronchodilators on CARDiac Autonomic Control in Chronic Obstructive Pulmonary Disease (COPD)
Official title: Effects of Long Acting Bronchodilators on CARDiac Autonomic Nervous System Control in Patients With COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
bronchodilatators
autonomic nervous system
cardiovascular system
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2016-08-18
Enrollment: 42
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

* patients with FEV1 / FVC \<70%

Exclusion Criteria:

* beta blocker
* supraventricular rhythm disorder
* previous history of respiratory disease other than COPD
* diabetes
* autonomic dysfunction
* dysautonomia
* renal failure
* long-term oxygen therapy
* history of psychiatric illness

Primary outcomes:
measure: Low-frequency (LF)/High-frequency (HF) ratio in supine position during a tilt table test after bronchodilators inhalation
timeFrame: 10 minutes
Secondary outcomes:
measure: Slope of baroreflex in supine position
timeFrame: 10 minutes
measure: LF / HF ratio derived from the spectral analysis of R-R intervals measured after verticalisation during a tilt table test
timeFrame: 10 minutes
measure: Total spectral power during a tilt table tes
timeFrame: 20 minutes
measure: Value of HF (gross value then normalized according to the average R-R interval) during a tilt table tes
timeFrame: 20 minutes
measure: RMSSD (Root Mean Square of the Successive Differences) index during a tilt table test
timeFrame: 20 minutes
measure: Variability in blood pressure during a tilt table test
timeFrame: 20 minutes
Other outcomes:
Locations:
city: Besançon
country: France
facility: Centre Hospitalier Régional Universitaire
Study officials:
affiliation: CHU Besançon
name: Matthieu VEIL-PICARD
role: PRINCIPAL_INVESTIGATOR
References: