Sympathetic Nerve ActivityPhase 2NCT02939469
Skin Sympathetic Nerve Activity and Cardiac Arrhythmias
A Phase 2 study testing Physiologic maneuvers in people with Sympathetic Nerve Activity, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
Since the invention of electrocardiogram (ECG), ECG has been an important part of clinical practice. A primary reason for the popularity of the ECG is that it is non-invasive and can be performed in any patient by placing electrodes on the skin. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Sympathetic Nerve Activity
- What is being tested?
- Physiologic maneuvers
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2016to 1 Nov 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-45 years of age
- BMI < 35 kg/m2
Who cannot join
- History of hypertension, diabetes, pulmonary disease, metabolic disease or heart failure
- Cardiac rhythm disorder, specifically: rhythm other than sinus
- Use of any medications other than common supplements
- Unable to perform handgrip exercise
- Pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: STTR Phase II : Skin Sympathetic Nerve Activity and Cardiac Arrhythmias
Since the invention of electrocardiogram (ECG), ECG has been an important part of clinical practice. A primary reason for the popularity of the ECG is that it is non-invasive and can be performed in any patient by placing electrodes on the skin. The present methods of ECG recording focus on detecting electrical signals from the heart. the investigators propose that with high frequency sampling and high pass filtering, the investigators can also record SNA from the skin. The somata of the subcutaneous sympathetic nerves on the skin are located at the ipsilateral cervical and stellate ganglia. Because the left stellate ganglion nerve activity (SGNA) is known to trigger cardiac arrhythmias, including AF, VF and VF, It is possible that skin SNA can also be used for arrhythmia prediction. the investigators tested that hypothesis in our preclinical studies (supported by R01 HL71140) using canine models. The results showed that subcutaneous nerve activity (SCNA) recorded with implanted electrodes can be used to estimate stellate ganglion nerve activity(SGNA) in normal dogs and in a canine model of ventricular arrhythmia and sudden death. the investigators also showed that SCNA is more accurate than heart rate variability in estimating cardiac sympathetic tone in ambulatory dogs with myocardial infarction.Therefore, SKNA and SCNA may be useful in estimating cardiac sympathetic tone. In addition to studying the autonomic mechanisms of cardiac arrhythmia, these new methods may have broad application in studying both cardiac and non-cardiac diseases. For example, sympathetic tone is important in the pathogenesis of heart failure, atherosclerosis, peripheral neuropathies, epilepsy, vasovagal syncope, renal failure, hypertension and many others diseases. Direct SKNA and SCNA recording may provide new approaches to study the mechanisms of these common diseases. SKNA recording may also have immediate clinical applications by assisting in the diagnosis and treatment of hyperhidrosis (sweaty palms), paralysis, stroke, diabetes, and neuromuscular diseases. It may be used to assist biofeedback monitoring performed by neurologists to control neuropsychiatric disorders. Because of these potential clinical and commercial applications, the investigators propose that this research project is significant.
- Innovation
- Using conventional electrodes on the skin to record SNA. The neuECG utilizes the conventional skin electrodes that are widely used in health care facilities. Skin SNA had been recorded using microneurography techniques, and had been estimated using cutaneous blood flow (vasodilator responses) skin temperature, skin conductance and sweat release. However, microneurography cannot be used in ambulatory patients. The other methods are not direct measurements of SNA. neuECG is the first method that can directly and non-invasively measure the SNA from the skin.
- Automated real-time signal processing. the investigators will develop signal processing software to automatically eliminate noise, such as that generated by muscle contraction, electrical appliances, body motion, respiration, and radiofrequency signals. The remaining signals are then processed to separately display in real time to provide health care providers a new method to instantly estimate sympathetic tone. The ECG signals are used for automated arrhythmia detection while the SNA signals are available for risk stratification. This approach allows us to improve and broaden the clinical application of Einthoven's original invention by simultaneous detecting ECG and SNA from the skin.
- SKNA patterns as new biomarkers. the investigators have identified unique SKNA patterns that precede the onset of human AF. If proven correct by Specific Aim 3, this new biomarker can help physicians to estimate the arrhythmia risk and to predict the efficacy of catheter ablation for AF.
Read the detailed description
Background Cardiac sympathetic innervation comes from the paravertebral cervical and thoracic ganglia. Among them, the stellate (cervicothoracic) ganglion is a major source of sympathetic innervation. It constantly connects with phrenic nerves and almost as often to the vagal nerves.37 The paravertebral ganglia also directly connect with spinal nerves, which connect with the intercostal nerves. These intercostal nerves split into ramus cutaneous lateralis and a deep branch to the musculus rectus abdominis. Histological studies of human skin biopsy confirmed the presence of abundant sympathetic nerves in arteriovenous anastomoses arrector pilorum muscles, and arterioles. Using horseradish peroxidase as tracer, Baron et al and Taniguchi et al found that all skin sensory and sympathetic neurons are located ipsilaterally. The sympathetic somata are located in the middle cervical and stellate ganglia as well as the thoracic ganglia. Because of the direct and extensive connections among various nerve structures, it is possible for the sympathetic nerves in the various structures to activate simultaneously. Therefore, the investigators hypothesized that SKNA recorded from the upper thorax can be used to estimate the cardiac sympathetic tone.
Utilize the differential frequency contents of ECG and SNA to record neuECG To preserve the signal and eliminate noise, the American Heart Association (AHA) standard recommendation for low pass filtering of the ECG is 150 Hz for adolescents and adults, and 250 Hz for children. Higher frequency signals, although known to be clinically important, are routinely eliminated by this low pass filtering. Because there is no need to record high frequency signals, the conventional ECG and Holter monitoring devices do not have a wide bandwidth and high sampling rate. neuECG recording takes a different approach. the investigators use equipment with wide bandwidth (2K Hz) and high sampling rate (4K/s-10K/s) to record the signals from the skin. The signal is then band passed between 0.5 Hz and 150 Hz to display ECG signal. The same signals are then high passed at > 150 Hz to reveal nerve activities. Figure 1 illustrates the above concept. It shows Fast Fourier Transform (FFT) analyses of the signals recorded from the skin. High pass filtering at 150 Hz eliminated the ECG signals. The remaining high frequency signals may contain both muscle and nerve activities. McAuley et al reported that the electromyography (EMG) usually has a frequency of <100 Hz. At most, small amounts of muscle activities could reach 400 Hz. By high pass filtering at 500 Hz, the EMG is eliminated but so are other signals with frequencies < 500 Hz. The standard high pass setting for microneurography study is 700 Hz. High pass filtering at 500 or 700 Hz increased the specificity but reduced the sensitivity of SKNA recording. The signal to noise ratio is reduced. However, the basic patterns of nerve discharges remain.
- Conditions
- Sympathetic Nerve Activity
- Being tested
- Physiologic maneuvers
- Keywords
- Sympathetic Nerve Activity, Skin Sympathetic Nerve Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physiologic maneuversOther
Subjects will perform
Valsalva maneuver Hand Grip Post exercise cuff occlusion Loud Noise and Skin pinch
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Sympathetic nerve activity | Experimental | Healthy volunteers will undergo microneurography, and non invasive sympathetic nerve activity by EKG analysis at baseline and in response to stress. Receives: Other: Physiologic maneuvers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Chane in Sympathetic nerve activity
Multi-unit recordings of sympathetic nerve activity will be obtained with single-use sterile
Measured: Change from baseline in sympathetic nerve activity at 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2016 (estimated)
- Study start1 Nov 2016
- Primary completion1 Nov 2018
- Study completion1 Nov 2018
Why it stopped: The PI passed away.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sympathetic Nerve ActivityStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Florian Rader, Cedars-Sinai Medical Center
- Investigators
- Ronald Victor, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02939469
- Sponsor's protocol ID
- Pro 42959
- Status last verified
- Jun 2019
- First submitted
- 11 Oct 2016
- Last updated
- 14 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- STTR Phase II : Skin Sympathetic Nerve Activity and Cardiac Arrhythmias
- ClinicalTrials.gov ID
- NCT02939469
- Acronym / sponsor ID
- Pro 42959
- Conditions
- Sympathetic Nerve Activity
- Keywords
- Sympathetic Nerve Activity, Skin Sympathetic Nerve Activity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The PI passed away.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 1 Nov 2018 (actual)
- First posted
- 20 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Since the invention of electrocardiogram (ECG), ECG has been an important part of clinical practice. A primary reason for the popularity of the ECG is that it is non-invasive and can be performed in any patient by placing electrodes on the skin. The present methods of ECG recording focus on detecting electrical signals from the heart. the investigators propose that with high frequency sampling and high pass filtering, the investigators can also record SNA from the skin. The somata of the subcutaneous sympathetic nerves on the skin are located at the ipsilateral cervical and stellate ganglia. Because the left stellate ganglion nerve activity (SGNA) is known to trigger cardiac arrhythmias, including AF, VF and VF, It is possible that skin SNA can also be used for arrhythmia prediction. the investigators tested that hypothesis in our preclinical studies (supported by R01 HL71140) using canine models. The results showed that subcutaneous nerve activity (SCNA) recorded with implanted electrodes can be used to estimate stellate ganglion nerve activity(SGNA) in normal dogs and in a canine model of ventricular arrhythmia and sudden death. the investigators also showed that SCNA is more accurate than heart rate variability in estimating cardiac sympathetic tone in ambulatory dogs with myocardial infarction.Therefore, SKNA and SCNA may be useful in estimating cardiac sympathetic tone. In addition to studying the autonomic mechanisms of cardiac arrhythmia, these new methods may have broad application in studying both cardiac and non-cardiac diseases. For example, sympathetic tone is important in the pathogenesis of heart failure, atherosclerosis, peripheral neuropathies, epilepsy, vasovagal syncope, renal failure, hypertension and many others diseases. Direct SKNA and SCNA recording may provide new approaches to study the mechanisms of these common diseases. SKNA recording may also have immediate clinical applications by assisting in the diagnosis and treatment of hyperhidrosis (sweaty palms), paralysis, stroke, diabetes, and neuromuscular diseases. It may be used to assist biofeedback monitoring performed by neurologists to control neuropsychiatric disorders. Because of these potential clinical and commercial applications, the investigators propose that this research project is significant.
- Innovation
- Using conventional electrodes on the skin to record SNA. The neuECG utilizes the conventional skin electrodes that are widely used in health care facilities. Skin SNA had been recorded using microneurography techniques, and had been estimated using cutaneous blood flow (vasodilator responses) skin temperature, skin conductance and sweat release. However, microneurography cannot be used in ambulatory patients. The other methods are not direct measurements of SNA. neuECG is the first method that can directly and non-invasively measure the SNA from the skin.
- Automated real-time signal processing. the investigators will develop signal processing software to automatically eliminate noise, such as that generated by muscle contraction, electrical appliances, body motion, respiration, and radiofrequency signals. The remaining signals are then processed to separately display in real time to provide health care providers a new method to instantly estimate sympathetic tone. The ECG signals are used for automated arrhythmia detection while the SNA signals are available for risk stratification. This approach allows us to improve and broaden the clinical application of Einthoven's original invention by simultaneous detecting ECG and SNA from the skin.
- SKNA patterns as new biomarkers. the investigators have identified unique SKNA patterns that precede the onset of human AF. If proven correct by Specific Aim 3, this new biomarker can help physicians to estimate the arrhythmia risk and to predict the efficacy of catheter ablation for AF.
Detailed description
Background Cardiac sympathetic innervation comes from the paravertebral cervical and thoracic ganglia. Among them, the stellate (cervicothoracic) ganglion is a major source of sympathetic innervation. It constantly connects with phrenic nerves and almost as often to the vagal nerves.37 The paravertebral ganglia also directly connect with spinal nerves, which connect with the intercostal nerves. These intercostal nerves split into ramus cutaneous lateralis and a deep branch to the musculus rectus abdominis. Histological studies of human skin biopsy confirmed the presence of abundant sympathetic nerves in arteriovenous anastomoses arrector pilorum muscles, and arterioles. Using horseradish peroxidase as tracer, Baron et al and Taniguchi et al found that all skin sensory and sympathetic neurons are located ipsilaterally. The sympathetic somata are located in the middle cervical and stellate ganglia as well as the thoracic ganglia. Because of the direct and extensive connections among various nerve structures, it is possible for the sympathetic nerves in the various structures to activate simultaneously. Therefore, the investigators hypothesized that SKNA recorded from the upper thorax can be used to estimate the cardiac sympathetic tone.
Utilize the differential frequency contents of ECG and SNA to record neuECG To preserve the signal and eliminate noise, the American Heart Association (AHA) standard recommendation for low pass filtering of the ECG is 150 Hz for adolescents and adults, and 250 Hz for children. Higher frequency signals, although known to be clinically important, are routinely eliminated by this low pass filtering. Because there is no need to record high frequency signals, the conventional ECG and Holter monitoring devices do not have a wide bandwidth and high sampling rate. neuECG recording takes a different approach. the investigators use equipment with wide bandwidth (2K Hz) and high sampling rate (4K/s-10K/s) to record the signals from the skin. The signal is then band passed between 0.5 Hz and 150 Hz to display ECG signal. The same signals are then high passed at > 150 Hz to reveal nerve activities. Figure 1 illustrates the above concept. It shows Fast Fourier Transform (FFT) analyses of the signals recorded from the skin. High pass filtering at 150 Hz eliminated the ECG signals. The remaining high frequency signals may contain both muscle and nerve activities. McAuley et al reported that the electromyography (EMG) usually has a frequency of <100 Hz. At most, small amounts of muscle activities could reach 400 Hz. By high pass filtering at 500 Hz, the EMG is eliminated but so are other signals with frequencies < 500 Hz. The standard high pass setting for microneurography study is 700 Hz. High pass filtering at 500 or 700 Hz increased the specificity but reduced the sensitivity of SKNA recording. The signal to noise ratio is reduced. However, the basic patterns of nerve discharges remain.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: Sympathetic nerve activity | Experimental | Other: Physiologic maneuversHealthy volunteers will undergo microneurography, and non invasive sympathetic nerve activity by EKG analysis at baseline and in response to stress. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Age 18-45 years of age
- BMI < 35 kg/m2
Key exclusion criteria (5 listed)
- History of hypertension, diabetes, pulmonary disease, metabolic disease or heart failure
- Cardiac rhythm disorder, specifically: rhythm other than sinus
- Use of any medications other than common supplements
- Unable to perform handgrip exercise
- Pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Physiologic maneuversSubjects will perform Valsalva maneuver Hand Grip Post exercise cuff occlusion Loud Noise and Skin pinch | Other | Experimental: Sympathetic nerve activity |
Primary outcome
Chane in Sympathetic nerve activity
Time frame: Change from baseline in sympathetic nerve activity at 2 hours
Multi-unit recordings of sympathetic nerve activity will be obtained with single-use sterile
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald Victor, MD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Physiologic maneuvers in people with Sympathetic Nerve Activity, run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Chane in Sympathetic nerve activity (time frame: Change from baseline in sympathetic nerve activity at 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2019.