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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Placebo; Drug: Indacaterol; Drug: Glycopyrronium; Drug: Tiotropium; Procedure: photoplethysmography

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 Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Besançon, France
    • Centre hospitalier régional universitaire

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low-frequency (LF)/High-frequency (HF) ratio in supine position during a tilt table test after bronchodilators inhalation	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.	10 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slope of baroreflex in supine position	Drugs vs placebo	10 minutes
LF / HF ratio derived from the spectral analysis of R-R intervals measured after verticalisation during a tilt table test	Drugs vs placebo	10 minutes
Total spectral power during a tilt table tes	Drugs vs placebo	20 minutes
Value of HF (gross value then normalized according to the average R-R interval) during a tilt table tes	Drugs vs placebo	20 minutes
RMSSD (Root Mean Square of the Successive Differences) index during a tilt table test	Drugs vs placebo	20 minutes
Variability in blood pressure during a tilt table test	Drugs vs placebo	20 minutes

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Investigators: Principal Investigator: Matthieu VEIL-PICARD, CHU Besançon

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (ACTUAL): June 1, 2021
• Study Completion (ACTUAL): June 1, 2021

Study Registration Dates

• First Submitted: August 11, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (ESTIMATE): August 18, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2021
• Last Update Submitted That Met QC Criteria: August 2, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: COPD; autonomic nervous system; cardiovascular system; bronchodilatators
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Glycopyrrolate; Tiotropium Bromide
• Other Study ID Numbers: P/2015/255

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO