Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Non-Invasive Bioelectronic Analytics (NIBA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04100486
Recruitment Status : Recruiting
First Posted : September 24, 2019
Last Update Posted : September 24, 2019
Sponsor:
Information provided by (Responsible Party):
Theodoros Zanos, Northwell Health

Brief Summary:
Biomarkers can be evaluated to provide information about disease presence or intensity and treatment efficacy. By recording these biomarkers through noninvasive clinical techniques, it is possible to gain information about the autonomic nervous system (ANS), which involuntarily regulates and adapts organ systems in the body. Machine learning and signal processing methods have made it possible to quantify the behavior of the ANS by statistically analyzing recorded signals. This work will aim to systematically measure ANS function by multiple modalities and use decoding algorithms to derive an index that reflects overall ANS function and/or balance in healthy able-bodied individuals. Additionally, this study will determine how transcutaneous auricular vagus nerve stimulation (taVNS), a noninvasive method of stimulating the vagus nerve without surgery, affects the ANS function. Data from this research will enable the possibility of detecting early and significant changes in ANS from "normal" homeostasis to diagnose disease onset and assess severity to improve treatment protocols.

Condition or disease Intervention/treatment
Autonomic Dysfunction Autonomic Imbalance Autonomic Nervous System Diseases Vagus Nerve Autonomic Disorder Other: Standing-Squatting-Standing Test Other: Deep Breathing Test Other: Cold Pressor Test Other: Cold Face Test Other: Valsalva Maneuver Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Show Show detailed description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 48 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: A Pilot Study to Quantify the Autonomic Nervous System Balance in Healthy, Able-Bodied Individuals
Actual Study Start Date : August 29, 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : September 2020

Group/Cohort Intervention/treatment
Healthy, Able-Bodied Individuals
This study will only enroll healthy, able-bodied individuals.
Other: Standing-Squatting-Standing Test
The participant will begin by actively standing for one minute, followed by a transition to a squat for one minute, and one last transition to one minute of standing.

Other: Deep Breathing Test
The participant will be asked to lay down for seven minutes and take long, controlled breaths at a rate within 4 to 10 breaths per minute.

Other: Cold Pressor Test
The participant will be asked to immerse their hand into ice water (1- 10°C) for up to three minutes, followed by removal of the hand from the bath and continuation for recording for a further three to five minutes. The participant will be informed that he or she can remove his or her hand at any point if there is discomfort.

Other: Cold Face Test
The cold stimulus will be applied with refrigerated gel-filled compresses places on the forehead and cheeks of the participant for one minute.
Other Name: Diving Reflex Text

Other: Valsalva Maneuver
The participant will be asked to inhale deeply, pinch his or her nose, close his or her mouth, and forcibly exhale, while bearing down with tight chest and stomach muscles, for approximately 10 to 15 seconds. The sensors will continue recording as the participant recovers to normal breathing over the next one minute.

Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)
The participant will receive electrical stimulation applied to their ear for five minutes. The threshold for stimulation will be determined before the test begins at a level that may elicit sensation (tickling, vibrating, pricking), but no pain. There is a possibility that the participant will receive sham stimulation, or inactive stimulation, for this test.
Other Name: Noninvasive Vagus Nerve Stimulation at the Ear




Primary Outcome Measures :
  1. Changes in Heart Rate (Electrocardiography) related to Autonomic Nervous System Perturbations [ Time Frame: 4 2-hour sessions over 2 weeks ]
    The primary objective is to measure changes in ANS balance in healthy able-bodied individuals by discovering a multi-modal index to quantify the activation status of the sympathetic and parasympathetic nervous systems during a battery of clinically relevant tasks. Changes in electrocardiography (EKG) signals will be measured to measure heart rates while purposefully activating the sympathetic (e.g. cold pressor test) or parasympathetic nervous systems (e.g. deep breathing) with safe, established tests to measure responses to changes in ANS function in healthy, able-bodied individuals. Heart rates will be assessed as percent change during tasks, with a comparison to baseline (before and after each autonomic test).

  2. Changes in Brain Activity (Electroencephalography) related to Autonomic Nervous System Perturbations [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Changes in electroencephalography (EEG) signals by a dry and noninvasive electrode cap will be measured to measure brain activity while purposefully activating the sympathetic (e.g. cold pressor test) or parasympathetic nervous systems (e.g. deep breathing) with safe, established tests to measure responses to changes in ANS function in healthy, able-bodied individuals. EEG activity will be analyzed by measuring changes in power in specific frequency bands (delta, theta, alpha, beta, and gamma). Brain activity will be assessed as percent change during tasks, with a comparison to baseline (before and after each autonomic test).

  3. Changes in Respiratory Rate related to Autonomic Nervous System Perturbations [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Changes in respiratory rate will be measured by a belt while purposefully activating the sympathetic (e.g. cold pressor test) or parasympathetic nervous systems (e.g. deep breathing) with safe, established tests to measure responses to changes in ANS function in healthy, able-bodied individuals. The belt stretches and relaxes during inspiration (inhalation) and experiation (exhalation), respectively, to infer respiration rate. Respiration changes will be assessed as percent change during tasks, with a comparison to baseline (before and after each autonomic test).

  4. Changes in Sweat Gland Activity (Galvanic Skin Response) related to Autonomic Nervous System Perturbations [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Changes in sweat gland activity will be measured by dry metal electrodes on two fingers while purposefully activating the sympathetic (e.g. cold pressor test) or parasympathetic nervous systems (e.g. deep breathing) with safe, established tests to measure responses to changes in ANS function in healthy, able-bodied individuals. The electrodes measure the galvanic skin response (GSR), a measure of electrical activity that changes depends on the sweat response. Sweat responses will be assessed as percent change during tasks, with a comparison to baseline (before and after each autonomic test).

  5. Changes in Blood Pressure related to Autonomic Nervous System Perturbations [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Changes in blood pressure will be measured by an inflatable cuff on one finger while purposefully activating the sympathetic (e.g. cold pressor test) or parasympathetic nervous systems (e.g. deep breathing) with safe, established tests to measure responses to changes in ANS function in healthy, able-bodied individuals. A wrist device is placed with a Velcro strap on the wrist to provide air and power for the finger cuff to inflate and deflate with changes in blood pressure. Blood pressure will be assessed as percent change during tasks, with a comparison to baseline (before and after each autonomic test).

  6. Changes in Skin Temperature related to Autonomic Nervous System Perturbations [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Changes in skin temperature will be measured by a circular probe (smaller than a dime) placed on the skin while purposefully activating the sympathetic (e.g. cold pressor test) or parasympathetic nervous systems (e.g. deep breathing) with safe, established tests to measure responses to changes in ANS function in healthy, able-bodied individuals. Temperature will be assessed as percent change during tasks, with a comparison to baseline (before and after each autonomic test).

  7. Changes in Pupil Size related to Autonomic Nervous System Perturbations [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Changes in pupil size will be measured by eye tracking glasses while purposefully activating the sympathetic (e.g. cold pressor test) or parasympathetic nervous systems (e.g. deep breathing) with safe, established tests to measure responses to changes in ANS function in healthy, able-bodied individuals. The glasses are easily wearable and mobile glasses with multiple small cameras to track gaze and pupil size. Pupil sizes will be assessed as percent change during tasks, with a comparison to baseline (before and after each autonomic test).


Secondary Outcome Measures :
  1. Changes in Heart Rate (Electrocardiography) due to taVNS [ Time Frame: 4 2-hour sessions over 2 weeks ]
    A secondary objective is to examine how the physiological measurements and the derived ANS index are affected by non-invasive taVNS. The efficacy and specificity of taVNS as it relates to autonomic perturbations will be analyzed while maintaining safety and tolerability in healthy, able-bodied individuals. Heart rates will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).

  2. Changes in Brain Activity (Electroencephalography) due to taVNS [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Power in EEG frequency bands will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).

  3. Changes in Respiratory Rate due to taVNS [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Respiratory rates will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).

  4. Changes in Sweat Gland Activity (Galvanic Skin Response) due to taVNS [ Time Frame: 4 2-hour sessions over 2 weeks ]
    GSR will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).

  5. Changes in Blood Pressure due to taVNS [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Blood pressure will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).

  6. Changes in Skin Temperature due to taVNS [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Skin temperature will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).

  7. Changes in Pupil Size due to taVNS [ Time Frame: 4 2-hour sessions over 2 weeks ]
    Pupil size will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The study will only enroll healthy able-bodied individuals. To be eligible to participate in this study, individuals must be between the ages of 18 and 60 years (to avoid changes in ANS with age), proficient in English, BMI less than 30 based on height and weight, and able and willing to provide informed consent and comply with the requirement of the study protocol.
Criteria

Inclusion Criteria:

  • Individuals between 18-60 years of age (to avoid changes in ANS with age)
  • Individuals that are considered English Proficient due to the study requirements to follow verbal commands
  • Able-bodied persons with no known health conditions
  • BMI < 30.0, based on height and weight (to limit known effects of high BMI on ANS activity [Costa et al., 2019])
  • Able and willing to give written informed consent and comply with the requirements of the study protocol

Exclusion Criteria:

  • History of any of the following: cardiac arrhythmia, coronary artery disease, autoimmune disease, chronic inflammatory disease, anemia, malignancy, depression, neurologic disease, diabetes mellitus, renal disease, dementia, psychiatric illness including active psychosis, or any other chronic medical condition
  • Evidence of active infection
  • Family history of inflammatory disease
  • Treatment with an anti-cholinergic medication, including over-the-counter medications for allergy and sleep-aid within the past 1 week, including all drugs with Amitriptyline, Atropine, Benztropine, Chlorpheniramine, Chlorpromazine, Clomipramine, Clozapine, Cyclobenzaprine, Cyproheptadine, Desipramine, Dexchlorpheniramine, Dicyclomine, Diphenhydramine (Benadryl), Doxepin, Fesoterodine, Hydroxyzine, Hyoscyamine, Imipramine, Meclizine, Nortriptyline, Olanzapine, Orphenadrine, Oxybutynin, Paroxetine, Perphenazine, Prochlorperazine, Promethazine, Protriptyline, Pseudoephedrine, Scopolamine, Thioridazine, Tolterodine, Trifluoperazine, and Trimipramine
  • Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants, deep brain stimulators, or vagus nerve stimulators
  • Current tobacco or nicotine use (to limit any potentially confounding effects of exposure to nicotine), which includes any use within the past 1 week
  • Chronic inflammatory disorders
  • Pre-existing neurological disease, which indicates any significant neurological condition, including multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's Disease, or stroke
  • Pregnancy or lactation (determined by self-report), as early pregnancy may potentially impact ANS measurements
  • Active ear infection (otitis media or externa) or any other afflictions of the ear
  • Any condition that, in the investigator's opinion, would jeopardize the participant's safety following exposure to a study intervention
  • Inability to comply with study procedures and methods
  • Prisoners

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04100486


Contacts
Layout table for location contacts
Contact: Shubham Debnath, PhD 5165620487 sdebnath@northwell.edu
Contact: Theodoros P Zanos, PhD 5165620484 tzanos@northwell.edu

Locations
Layout table for location information
United States, New York
The Feinstein Institutes for Medical Research Recruiting
Manhasset, New York, United States, 11030
Contact: Shubham Debnath, PhD    516-562-0487    sdebnath@northwell.edu   
Principal Investigator: Theodoros P Zanos, PhD         
Sponsors and Collaborators
Northwell Health
Investigators
Layout table for investigator information
Principal Investigator: Theodoros P Zanos, PhD Northwell Health

Publications:
Addorisio, M. E., Imperato, G. H., de Vos, A. F., Forti, S., Goldstein, R. S., Pavlov, V. A., … Chavan, S. S. (2019). Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear. Bioelectronic Medicine, 5(1), 4. https://doi.org/10.1186/s42234-019-0020-4
Freeman, R., & Chapleau, M. W. (2013). Testing the Autonomic Nervous System. In Handbook of Clinical Neurology (1st ed., Vol. 115). https://doi.org/10.1055/s-2004-817725
Gibbons, C. H., Cheshire, W. P., & Fife, T. D. (2014). Autonomic Testing. American Academy of Neurology, (October), 1-10. Retrieved from https://pdfs.semanticscholar.org/2ca5/0a89aa14e473b4ba3db9eeb7434eaf0b9c6f.pdf
Krassioukov, A., Biering-Sorensen, F., Donovan, W., Kennelly, M., Kirshblum, S., Krogh, K., … Wecht, J. (2012). International standards to document remaining autonomic function after spinal cord injury. Spinal Cord, 47(1), 36-43. https://doi.org/10.1038/sc.2008.121
Verrotti, A., Prezioso, G., Scattoni, R., & Chiarelli, F. (2014). Autonomic neuropathy in diabetes mellitus. Frontiers in Endocrinology, 5. https://doi.org/10.3389/fendo.2014.00205
Weimer, L. H. (2010). Autonomic testing. The Neurologist, 16(4), 215-224. https://doi.org/10.1016/S1567-4231(09)70083-8

Layout table for additonal information
Responsible Party: Theodoros Zanos, Assistant Professor, Neural and Data Science Laboratory, Northwell Health
ClinicalTrials.gov Identifier: NCT04100486    
Other Study ID Numbers: 19-0461
First Posted: September 24, 2019    Key Record Dates
Last Update Posted: September 24, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Theodoros Zanos, Northwell Health:
Vagus Nerve Stimulation
Noninvasive
Autonomic Nervous System
Biosensors
Vitals Monitoring
Machine Learning
Deep Learning
Additional relevant MeSH terms:
Layout table for MeSH terms
Autonomic Nervous System Diseases
Primary Dysautonomias
Nervous System Diseases