Brief Summary

The project will be pursued in our respiratory, autonomic nervous system physiology laboratory (Respiratory, autonomic nervous system physiology laboratory, Department of Pneumology and Intensive Care Medicine, RWTH Aachen University Hospital; Head of Department: Professor Michael Dreher). Overactivity of the sympathetic nerve activity (SNA) axis with "centrally" increased heart rate and peripheral vasoconstriction is a known phenomenon in patients with systolic heart failure (HF) and has recently been described in patients with primary lung disease as seen in chronic obstructive pulmonary disease (COPD). However, systematic analyses on this clinically relevant topic are currently lacking. Thus, using a comprehensive, multimodal approach and state-of-the-art technology, this research project is designed to determine the extent and nature of increased SNA in COPD (AIM 1) and evaluate the underlying mechanisms (AIM 2). The project will address the following hypotheses:

1.In COPD, concomitant obstructive sleep apnea is independently associated with increased SNA.
2.Precapillary pulmonary hypertension (PH), inspiratory muscle dysfunction and systemic inflammation describe a COPD phenotype characterised by increased SNA with a different subtype.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

135

participants targeted

Target at P50-P75 for all trials

Timeline

31mo left

Started May 2022

Longer than P75 for all trials

Geographic Reach

1 country

1 active site

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

6.6 years study duration

Study Progress61%

May 2022Dec 2028

First Submitted

Initial submission to the registry

April 15, 2021

Completed

4 days until next milestone

First Posted

Study publicly available on registry

April 19, 2021

Completed

1.1 years until next milestone

Study Start

First participant enrolled

May 10, 2022

Completed

6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2028

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

January 28, 2026

Status Verified

January 1, 2026

Enrollment Period

6.6 years

First QC Date

April 15, 2021

Last Update Submit

January 26, 2026

Conditions

COPD Sympathetic Nervous System Diseases Catecholamine; Overproduction

Outcome Measures

Primary Outcomes (2)

Assessments of the sympathetic nerve activity axis (Non invasive)
sympathovagal balance (SVB), HRV and dBPV will be analysed using a 3-lead electrocardiogram (sampling rate 1000Hz) and a continuous non-invasive arterial blood pressure signal (CNAP® technology, sampling rate 100Hz). HRV (ms2 based on continuously recorded variability in RR intervals) and (diastolic) BPV (expressed as mmHg2 based on continuously recorded variability in diastolic BP) will be computed by time domain analysis and by frequency domain analysis and presented as the high frequency component (HF; 0.15-0.4 Hz), low frequency component (LF; 0.04-0.15 Hz), their relative ratio (LF/HF), and the very low frequency component (VLF; 0.0-0.04 Hz) for both HRV and dBPV .
2 years
Assessments of the sympathetic nerve activity axis (Invasive)
Muscle SNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve Plasma catecholamines will be assessed Muscle SNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve Plasma catecholamines will be assessed Muscle SNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve. Plasma catecholamines will be assessed
2 years

Secondary Outcomes (4)

OSA severity
2 years
Determination of PH and right HF severity
2 years
Comprehensive lung function and inspiratory muscle function testing as previously described by our group
2 years
Assessment of systemic inflammation
2 years

Study Arms (2)

COPD patients (n=100)

The following parameters will be determined in 100 consecutive patients with COPD without established cardiovascular disease (i.e. without an indication for beta blocker therapy or other pharmacological treatments attacking on the neurohormonal pathways like angiotensin-converting enzyme inhibitors or mineralocorticoid receptor antagonists). 1. OSA severity. 2. Determination of PH and right HF severity (defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography; 3. Comprehensive lung function and inspiratory muscle function testing ;Assessment of daytime hypoxia (PaO2 \<55 mmHg) and hypercapnia (PaCO2 \>45 mmHg) using capillary blood gas analysis; 4. Assessment of systemic inflammation

Diagnostic Test: Assessments of the sympathetic nerve activity axisDiagnostic Test: OSA severityDiagnostic Test: Determination of PH and right HF severityDiagnostic Test: Comprehensive lung function and inspiratory muscle function testing.Diagnostic Test: Assessment of systemic inflammation

Controls (n=35)

(and in a group of healthy controls \[3:1\] matched for age, sex and BMI).

Interventions

Determination of PH and right HF severityDIAGNOSTIC_TEST

(defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography