- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04849806
Sympathetic Nerve Activity Predictors in Patients With Chronic Obstructive Pulmonary Disease (SNAP-COPD)
Dissecting the Nature and Determinants of Sympathetic Nerve Activity in Patients With COPD
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:
- In COPD, concomitant obstructive sleep apnea is independently associated with increased SNA.
- Precapillary pulmonary hypertension (PH), inspiratory muscle dysfunction and systemic inflammation describe a COPD phenotype characterised by increased SNA with a different subtype.
Study Overview
Status
Intervention / Treatment
Detailed Description
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 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:
- In COPD, concomitant OSA with poor sleep is independently associated with increased SNA,.
- 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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Michael Dreher, Professor
- Phone Number: 88763 +492418088763
- Email: mdreher@ukaachen.de
Study Contact Backup
- Name: Jens Dr. Spiesshoefer, MD
- Phone Number: +492418037036
- Email: jspiesshoefe@ukaachen.de
Study Locations
-
-
-
Aachen, Germany
- Recruiting
- RWTH Aachen University
-
Contact:
- Michael Dreher, Professor
- Phone Number: 88763 +4924180
- Email: mdreher@ukaachen.de
-
Contact:
- Jens Spiesshoefer, MD
- Phone Number: 37036 +4924180
- Email: jspiesshoefer@ukaachen.de
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Age ≥ 18
- Ability and willingness to give informed consent to participate in the study
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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).
|
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 is defined as apnoea-hypopnoea index [AHI] >15/h and obstructive apnoea index [OAI] >5/h) and sleep architecture
(defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography
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.
Based on blood samples taken.
|
Controls (n=20)
(and in a group of healthy controls [3:1] matched for age, sex and BMI).
|
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 is defined as apnoea-hypopnoea index [AHI] >15/h and obstructive apnoea index [OAI] >5/h) and sleep architecture
(defined as tricuspid annular plane systolic excursion ≤14 mm) and pulmonary arterial pressure (PAsys) using transthoracic echocardiography
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.
Based on blood samples taken.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessments of the sympathetic nerve activity axis (Non invasive)
Time Frame: 2 years
|
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)
Time Frame: 2 years
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
OSA severity
Time Frame: 2 years
|
See above
|
2 years
|
Determination of PH and right HF severity
Time Frame: 2 years
|
See above
|
2 years
|
Comprehensive lung function and inspiratory muscle function testing as previously described by our group
Time Frame: 2 years
|
See above
|
2 years
|
Assessment of systemic inflammation
Time Frame: 2 years
|
See above
|
2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Michael Dreher, Professor, RWTH Aachen University
- Principal Investigator: Jens Spiesshoefer, MD, RWTH Aachen University
- Study Chair: Binaya Regmi, MD, RWTH Aachen University
Publications and helpful links
General Publications
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTCA 20-423
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on COPD
-
University Medical Center GroningenCompleted
-
Istituto Nazionale di Ricovero e Cura per AnzianiRecruiting
-
Bio-Sensing Solutions S.L. (DyCare)Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Centre...Not yet recruiting
-
Sir Run Run Shaw HospitalRecruiting
-
University Hospital, BrestRecruiting
-
The First Affiliated Hospital of Guangzhou Medical...Recruiting
-
Association des Réseaux BronchioliteLaboratoire Système et Matériaux pour la Mécatronique (SYMME)Recruiting
-
Baylor Research InstituteNot yet recruiting
-
Polytechnic Institute of PortoNippon Gases PortugalRecruiting
Clinical Trials on Assessments of the sympathetic nerve activity axis
-
Université Catholique de LouvainErasme University HospitalUnknownHeart Rate Variability | Autonomic Nervous System | Muscle Sympathetic Nerve ActivityBelgium
-
University of Wisconsin, MadisonUnited States Department of DefenseRecruitingBrain Blood Flow | Neurovascular ControlUnited States
-
Kolding SygehusAarhus University HospitalCompletedPostoperative Pain | Regional AnesthesiaDenmark
-
University of MinnesotaRecruitingHypertension | Menopause | Blood Pressure | Menopause, PrematureUnited States
-
Peking Union Medical College HospitalCompletedAnalgesia | Total Knee Arthroplasty | Nerve BlockChina
-
Frank BochmannActive, not recruitingCataract Senile | AstigmatismSwitzerland
-
Swiss Federal Institute of TechnologyCLINICA HILDEBRAND CENTRO DI RIABILITAZIONE BRISSAGO; Neurocentro - Istituto...CompletedParkinson DiseaseSwitzerland
-
University of Sao Paulo General HospitalFundação de Amparo à Pesquisa do Estado de São PauloCompleted
-
University Hospital, MontpellierReims University Hospital; Institute for Neurosciences of Montpellier U1051Completed
-
Tampere University HospitalCompletedSignificance of Latissimus Dorsi Flap Innervation in Delayed Breast Reconstruction