Sympathetic Nerve Activity Predictors in Patients With Chronic Obstructive Pulmonary Disease
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorRWTH Aachen University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age ≥ 18
Ability and willingness to give informed consent to participate in the study
Disqualifiers
Atrial fibrillation
Active pacing of the heart by a cardiac pacemaker (i.e. no intrinsic heart rate)
Clinically pre-established cardiovascular disease (e.g. arterial hypertension or systolic heart failure)
In-patient stay in the hospital within the last 4 weeks prior to the study examination date
Trial population
COPD patients (n=60) Controls (n=20) COPD patients without an established cardiovascular disease will be enrolled and the extent, nature and mechanism of SNA increase compared with healthy controls matched in a 3:1 ratio for age, sex and body mass index (BMI).
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
Assessments of the sympathetic nerve activity axis
Diagnostic testFor assessment 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 . Muscle SNA will be recorded via a tungsten microelectrode carefully placed in the peroneal nerve. Plasma catecholamines will also be assessed.
OSA severity
Diagnostic testOSA is defined as apnoea-hypopnoea index \[AHI\] \>15/h and obstructive apnoea index \[OAI\] \>5/h) and sleep architecture
Determination of PH and right HF severity
Diagnostic test(defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography
Comprehensive lung function and inspiratory muscle function testing.
Diagnostic testRespiratory Muscle strength and function testing as previously established by our group and Assessment of daytime hypoxia (PaO2 \<55 mmHg) and hypercapnia (PaCO2 \>45 mmHg) using capillary blood gas analysis.
Assessment of systemic inflammation
Diagnostic testBased on blood samples taken.
Treatment groups
135 Participants
are divided into 2 treatment groupsGroup A: COPD patients (n=100)5 interventions
Group B: Controls (n=35)5 interventions
Trial outcomes
Primary outcomes
1
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 .
Time frame
2 years2
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
Time frame
2 yearsSecondary outcomes
1
OSA severity
See above
Time frame
2 years2
Determination of PH and right HF severity
See above
Time frame
2 years3
Comprehensive lung function and inspiratory muscle function testing as previously described by our group
See above
Time frame
2 years4
Assessment of systemic inflammation
See above
Time frame
2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
RWTH Aachen University
Lead sponsor
DFG - Deutsche Forschungs Gemeinschaft (German Research Foundation)
Collaborator
Source ClinicalTrials.gov