Effects of Long Acting Bronchodilators on CARDiac Autonomic Nervous System Control in Patients With COPD
Overview
- Phase
- Phase 4
- Intervention
- Indacaterol
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- Centre Hospitalier Universitaire de Besancon
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Low-frequency (LF)/High-frequency (HF) ratio in supine position during a tilt table test after bronchodilators inhalation
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •patients with FEV1 / FVC \<70%
Exclusion Criteria
- •beta blocker
- •supraventricular rhythm disorder
- •previous history of respiratory disease other than COPD
- •autonomic dysfunction
- •dysautonomia
- •renal failure
- •long-term oxygen therapy
- •history of psychiatric illness
Arms & Interventions
Arm 1
The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo
Intervention: Indacaterol
Arm 1
The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo
Intervention: Glycopyrronium
Arm 1
The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo
Intervention: Tiotropium
Arm 1
The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo
Intervention: Placebo
Arm 1
The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo
Intervention: photoplethysmography
Arm 2
The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol
Intervention: Indacaterol
Arm 2
The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol
Intervention: Glycopyrronium
Arm 2
The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol
Intervention: Tiotropium
Arm 2
The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol
Intervention: Placebo
Arm 2
The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol
Intervention: photoplethysmography
Arm 3
The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium,
Intervention: Indacaterol
Arm 3
The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium,
Intervention: Glycopyrronium
Arm 3
The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium,
Intervention: Tiotropium
Arm 3
The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium,
Intervention: Placebo
Arm 3
The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium,
Intervention: photoplethysmography
Arm 4
The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium
Intervention: Indacaterol
Arm 4
The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium
Intervention: Glycopyrronium
Arm 4
The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium
Intervention: Tiotropium
Arm 4
The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium
Intervention: Placebo
Arm 4
The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium
Intervention: photoplethysmography
Outcomes
Primary Outcomes
Low-frequency (LF)/High-frequency (HF) ratio in supine position during a tilt table test after bronchodilators inhalation
Time Frame: 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 Outcomes
- Value of HF (gross value then normalized according to the average R-R interval) during a tilt table tes(20 minutes)
- RMSSD (Root Mean Square of the Successive Differences) index during a tilt table test(20 minutes)
- Variability in blood pressure during a tilt table test(20 minutes)
- Slope of baroreflex in supine position(10 minutes)
- LF / HF ratio derived from the spectral analysis of R-R intervals measured after verticalisation during a tilt table test(10 minutes)
- Total spectral power during a tilt table tes(20 minutes)