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

Sponsor

Centre Hospitalier Universitaire de Besancon (Other)

Overall Status

Completed

CT.gov ID

NCT02872090

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Indacaterol Drug: Glycopyrronium Drug: Tiotropium Drug: Placebo Procedure: photoplethysmography	Phase 4

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effects of Long Acting Bronchodilators on CARDiac Autonomic Nervous System Control in Patients With COPD

Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Jun 1, 2021

Actual Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 The patients receive once a week during 4 weeks, in the order: indacaterol, tiotropium, glycopyrronium and placebo	Drug: Indacaterol inhalation Drug: Glycopyrronium inhalation Drug: Tiotropium inhalation Drug: Placebo Procedure: photoplethysmography inhalation
Experimental: Arm 2 The patients receive once a week during 4 weeks, in the order: tiotropium, glycopyrronium, placebo and indacaterol	Drug: Indacaterol inhalation Drug: Glycopyrronium inhalation Drug: Tiotropium inhalation Drug: Placebo Procedure: photoplethysmography inhalation
Experimental: Arm 3 The patients receive once a week during 4 weeks, in the order: glycopyrronium, placebo, indacaterol and tiotropium,	Drug: Indacaterol inhalation Drug: Glycopyrronium inhalation Drug: Tiotropium inhalation Drug: Placebo Procedure: photoplethysmography inhalation
Experimental: Arm 4 The patients receive once a week during 4 weeks, in the order: placebo, indacaterol and tiotropium and glycopyrronium	Drug: Indacaterol inhalation Drug: Glycopyrronium inhalation Drug: Tiotropium inhalation Drug: Placebo Procedure: photoplethysmography inhalation

Outcome Measures

Primary Outcome Measures

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

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
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