Effects of Long Acting Bronchodilators on CARDiac Autonomic Control in Chronic Obstructive Pulmonary Disease (COPD)
- Conditions
- Chronic Obstructive Pulmonary Disease
- Interventions
- Registration Number
- NCT02872090
- Lead Sponsor
- Centre Hospitalier Universitaire de Besancon
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- patients with FEV1 / FVC <70%
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm 4 photoplethysmography The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium Arm 2 photoplethysmography The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol Arm 4 Placebo The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium Arm 2 Placebo The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol Arm 1 Placebo The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo Arm 1 photoplethysmography The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo Arm 3 Glycopyrronium The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium, Arm 3 Placebo The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium, Arm 3 photoplethysmography The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium, Arm 1 Tiotropium The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo Arm 1 Indacaterol The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo Arm 1 Glycopyrronium The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo Arm 2 Indacaterol The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol Arm 2 Glycopyrronium The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol Arm 2 Tiotropium The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol Arm 3 Indacaterol The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium, Arm 3 Tiotropium The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium, Arm 4 Indacaterol The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium Arm 4 Glycopyrronium The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium Arm 4 Tiotropium The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium
- Primary Outcome Measures
Name Time Method Low-frequency (LF)/High-frequency (HF) ratio in supine position during a tilt table test after bronchodilators inhalation 10 minutes For each patient, the LF/HF ratio after inhalation of an active drug (indacaterol or glycopyrronium or tiotropium) will be compared to LF / HF ratio measured after inhalation of a placebo.
- Secondary Outcome Measures
Name Time Method Total spectral power during a tilt table tes 20 minutes Drugs vs placebo
Value of HF (gross value then normalized according to the average R-R interval) during a tilt table tes 20 minutes Drugs vs placebo
RMSSD (Root Mean Square of the Successive Differences) index during a tilt table test 20 minutes Drugs vs placebo
Variability in blood pressure during a tilt table test 20 minutes Drugs vs placebo
Slope of baroreflex in supine position 10 minutes Drugs vs placebo
LF / HF ratio derived from the spectral analysis of R-R intervals measured after verticalisation during a tilt table test 10 minutes Drugs vs placebo
Trial Locations
- Locations (1)
Centre Hospitalier Régional Universitaire
🇫🇷Besançon, France