Skin Sympathetic Nerve Activity and Cardiac Arrhythmias

NCT02939469 | Withdrawn Phase 2

• 1 other identifier: Pro 42959
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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. b. 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.

Conditions

Sympathetic Nerve Activity

Keywords

Sympathetic Nerve Activity; Skin Sympathetic Nerve Activity

Outcome Measures

Primary Outcomes (1)

• Chane in Sympathetic nerve activity

  Multi-unit recordings of sympathetic nerve activity will be obtained with single-use sterile

  Change from baseline in sympathetic nerve activity at 2 hours

Study Arms (1)

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.

Other: Physiologic maneuvers

Interventions

Physiologic maneuvers OTHER

Subjects will perform Valsalva maneuver Hand Grip Post exercise cuff occlusion Loud Noise and Skin pinch

Experimental: Sympathetic nerve activity

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 years of age
• BMI \< 35 kg/m2

You may not qualify if:

• 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

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Study Officials

• Ronald Victor, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Director, Clinic for Hypertrophic Cardiomyopathy and Aortopathies, Smidt Heart Institute

Study Record Dates

• First Submitted: October 11, 2016
• First Posted: October 20, 2016
• Study Start: November 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: June 14, 2019

Record last verified: 2019-06

Locations

US (1)