Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, bronchodilatators, autonomic nervous system, cardiovascular system
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).
Interventions
DRUGIndacaterol
inhalation
DRUGGlycopyrronium
inhalation
DRUGTiotropium
inhalation
DRUGPlacebo
PROCEDUREphotoplethysmography
inhalation
Sponsors
Centre Hospitalier Universitaire de Besancon
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Slope of baroreflex in supine position | 10 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 |
| Value of HF (gross value then normalized according to the average R-R interval) during a tilt table tes | 20 minutes | Drugs vs placebo |
Countries
France
Outcome results
None listed