Sympathetic Nerve Activity Predictors in Patients With Chronic Obstructive Pulmonary Disease
NCT ID: NCT04849806
Last Updated: 2023-11-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
80 participants
OBSERVATIONAL
2022-05-10
2024-08-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Overactivity of the sympathetic nerve activity (SNA) axis 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).
Thus, insights into the nature of and factors involved in increased SNA in COPD are urgently needed.
Potentially obstructive sleep apnea (OSA) with not only repetitive obstructions but also additional hypoxia and poor sleep quality additively increase SNA in COPD. In addition, inspiratory muscle dysfunction (if adequately measured by magnetic diaphragm stimulation studies and comprehensive diaphragm ultrasound) with related hypercapnia, pulmonary hypertension (PH) and systemic inflammation all likely also impact on SNA in 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 OSA with poor sleep is independently associated with increased SNA,.
2. PH, inspiratory muscle dysfunction and systemic inflammation describe a COPD phenotype characterised by increased SNA, manifesting differently.
To test these hypotheses 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).
Invasive assessment of muscle SNA to the point of single unit recordings with analysis of single postganglionic sympathetic firing, and hence SNA drive to the peripheral vasculature, is the gold standard for quantification of SNA in humans but is only available in a few centres worldwide because it is costly, time consuming and requires a high level of training.
A small substudy will investigate the short term acute treatment effects of non-invasive ventilation and oxygen supplementation on SNA in patients with COPD.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
CASE_CONTROL
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
COPD patients (n=60)
The following parameters will be determined in 60 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
Assessments of the sympathetic nerve activity axis
For 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
OSA 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
(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.
Respiratory 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
Based on blood samples taken.
Controls (n=20)
(and in a group of healthy controls \[3:1\] matched for age, sex and BMI).
Assessments of the sympathetic nerve activity axis
For 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
OSA 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
(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.
Respiratory 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
Based on blood samples taken.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Assessments of the sympathetic nerve activity axis
For 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
OSA 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
(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.
Respiratory 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
Based on blood samples taken.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Ability and willingness to give informed consent to participate in the study
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
RWTH Aachen University
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Jens Spießhöfer
Jens Spiesshoefer, MD, PhD Candidate, Group head Respiratory Physiology
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Michael Dreher, Professor
Role: STUDY_DIRECTOR
RWTH Aachen University
Jens Spiesshoefer, MD
Role: PRINCIPAL_INVESTIGATOR
RWTH Aachen University
Binaya Regmi, MD
Role: STUDY_CHAIR
RWTH Aachen University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
RWTH Aachen University
Aachen, , Germany
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Spiesshoefer J, Becker S, Tuleta I, Mohr M, Diller GP, Emdin M, Florian AR, Yilmaz A, Boentert M, Giannoni A. Impact of Simulated Hyperventilation and Periodic Breathing on Sympatho-Vagal Balance and Hemodynamics in Patients with and without Heart Failure. Respiration. 2019;98(6):482-494. doi: 10.1159/000502155. Epub 2019 Aug 28.
Spiesshoefer J, Herkenrath S, Henke C, Langenbruch L, Schneppe M, Randerath W, Young P, Brix T, Boentert M. Evaluation of Respiratory Muscle Strength and Diaphragm Ultrasound: Normative Values, Theoretical Considerations, and Practical Recommendations. Respiration. 2020;99(5):369-381. doi: 10.1159/000506016. Epub 2020 May 12.
Spiesshoefer J, Henke C, Herkenrath S, Brix T, Randerath W, Young P, Boentert M. Transdiapragmatic pressure and contractile properties of the diaphragm following magnetic stimulation. Respir Physiol Neurobiol. 2019 Aug;266:47-53. doi: 10.1016/j.resp.2019.04.011. Epub 2019 Apr 25.
Dreher M, Neuzeret PC, Windisch W, Martens D, Hoheisel G, Groschel A, Woehrle H, Fetsch T, Graml A, Kohnlein T. Prevalence Of Chronic Hypercapnia In Severe Chronic Obstructive Pulmonary Disease: Data From The HOmeVent Registry. Int J Chron Obstruct Pulmon Dis. 2019 Oct 18;14:2377-2384. doi: 10.2147/COPD.S222803. eCollection 2019.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CTCA 20-423
Identifier Type: -
Identifier Source: org_study_id