Autonomic DysfunctionNIBANCT04100486
Non-Invasive Bioelectronic Analytics
An observational study of Autonomic Dysfunction and Autonomic Imbalance, run by Northwell Health at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Autonomic Dysfunction, Autonomic Imbalance, Autonomic Nervous System Diseases
- What is being tested?
- Standing-Squatting-Standing Test, Deep Breathing Test and Cold Pressor Test
- Type of treatment
- Medical device
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Aug 2019to Jul 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
The Feinstein Institutes for Medical Research
Manhasset, New York, 11030
About this study
Official title: A Pilot Study to Quantify the Autonomic Nervous System Balance in Healthy, Able-Bodied Individuals
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.
Read the detailed description
Biomarkers that reflect disease presence or intensity, or treatment efficacy are central to medical advancements. Recorded biomarkers provide information about physiological processes regulated by the autonomic nervous system (ANS), which include blood pressure, heart rate, sweating, and body temperature. The ANS has two major divisions: sympathetic and parasympathetic systems. Most organs receive reciprocal input from both systems to achieve homeostasis through ANS balance. This regulation occurs without conscious control (i.e., autonomously). Dysregulation of the ANS can occur as the result of disorders or injuries, including diabetes, sepsis, spinal cord injuries (SCI), Parkinson's disease, and many other conditions.
The ANS is the part of the nervous system that regulates and integrates bodily functions that typically run involuntary, particularly internal organs including blood vessels, lungs, pupils, heart, sweat, and salivary glands. Along with immunological systems, it controls and adapts homeostasis of the internal environment based on changes in the external environment. Disturbances in autonomic regulation have been described in a variety of diseases and disorders, including those that directly affect the nervous system, such as spinal cord injuries and stroke, and those that afflict other organ systems, such as sepsis and infection, rheumatoid arthritis, Crohn's disease, diabetes mellitus, and numerous heart conditions. This dysregulation manifests differently for each of these conditions, even inconsistently across patients, and the significance of symptoms due to ANS dysfunction are not well understood.
The ANS can be divided into two major branches: the sympathetic and parasympathetic systems. All internal organs are innervated by one or both component systems through the ANS main conduits, which include the brainstem, spinal cord, and cranial nerves, such as the vagus nerve. The branches typically function opposite and complementary of each other; physiological changes associated with the sympathetic system include accelerating heart rate, dilating pupils, and perspiration, while the parasympathetic system slows the heart, lowers blood pressure, and relaxes muscles. Both systems work in tandem to modulate and maintain blood pressure, vagal tone, heart rate, respiration, and cardiac contractility. While both systems operate to maintain homeostasis, the sympathetic system can be considered a quick response and mobilizing system, while the parasympathetic is a more slowly activated and dampening system.
Instead of measuring the ANS directly from the central or peripheral nervous system through invasive implants, it is possible to record physiological signals through advances in noninvasive clinical testing. Laboratories are able to test autonomic function and rely on batteries of accepted, noninvasive tests. According to the American Academy of Neurology (AAN), standard techniques of autonomic testing include measuring heart rate and blood pressure variability during deep breathing, tilt table, and the Valsalva maneuver to assess cardiovagal (parasympathetic) and sudomotor (sympathetic) function. It is straightforward to add to the limited necessary equipment (blood pressure cuff, electrocardiogram [ECG]) by including electroencephalography (EEG) to measure brain activity, electromyography (EMG) to measure muscle activity, and eye tracking glasses to measure pupillometry during this battery. All noninvasive signals can be measured during controlled perturbations to characterize the ANS. Assessment of ANS function is now used in multiple disciplines, including neurology, cardiology, psychology, psychophysiology, obstetrics, anesthesiology, and psychiatry.
Neural reflexes control responses in the cardiovascular, pulmonary, gastrointestinal, renal, hepatic, and endocrine systems. The vagus nerve-based inflammatory reflex is of particularly interest at the Feinstein Institute for Medical Research and has been shown to regulate immune function. The nervous system interacts with the immune system by this pathway; molecular mediators of innate immunity activate afferent signals in the vagus nerve to the brainstem, which sends efferent signals down the vagus nerve to regulate inflammation and cytokine release. Vagus nerve stimulation (VNS) has been shown to decrease production and release of pro-inflammatory cytokines; bioelectronic devices have been used in preclinical and pilot clinical trials to reduce inflammation in patients with rheumatoid arthritis and Crohn's disease.
The auricular branch of the vagus nerve comes from the vagus and innervates cutaneous areas of the outer ear. Transcutaneous auricular vagus nerve stimulation (taVNS) offers a non-invasive means of stimulating the vagus nerve without surgical intervention. The device consists of a clip that supplies electrical signals to processes of the auricle, and it has been used in previous clinical studies for multiple conditions, including refractory epilepsy, depression, pre-diabetes, tinnitus, memory, stroke, oromotor dysfunction, and rheumatoid arthritis, with additional studies planned for therapy or treatment of stroke, atrial fibrillation, and heart failure. These studies have used a range of electrical stimulation settings and sites; the mechanism of taVNS and responses are not well understood, as well as the effects of changes in stimulation parameters on ANS.
Recently, application of machine learning models and decoding algorithms permits utilizing commonly used clinical measurement of physiological signals to better understand broader phenomena of autonomic function and dysregulation. Research has been focused on developing quantitative standards based on biomarkers to aid with diagnosis, prognosis, and estimates of treatment efficacy. Autonomic data could potentially capture objective measures of disease states, and machine learning techniques can be used to extract relevant features towards building a predictive model of ANS balance. By training such a model on recordings from healthy, able-bodied individuals, the investigators plan to characterize ANS balance, and then apply this model to new data sets and individuals to diagnose or predict disease states.
Modern methods of computational science have been used to decode complex clinical and experimental data by detecting patterns, classifying signals, and extracting information towards new knowledge. Through signal processing techniques, it has been possible to decode autonomic nervous system signals conveyed through the vagus nerve by identifying groups of vagal neurons that fire in response to the administration of specific cytokines. Additionally, machine learning has been used to quantify clinical pain using multimodal autonomic metrics and neuroimaging, and large-scale ambulatory data has been used to monitor physiological signals and develop multi-sensor models to detect stress in daily life.
Additionally, the investigators want to examine how these measurements are affected by the use of non-invasive transcutaneous electrical stimulation of the vagus nerve. Stimulation of the vagus nerve by a surgically implanted stimulator regulates and suppresses pro-inflammatory cytokine release. This has now been used in a successful clinical trial to treat rheumatoid arthritis and Crohn's disease. Non-invasive transcutaneous stimulation of the vagus nerve has also been showing promising early results, indicating that non-invasive methods of activating a specific part of the autonomic nervous system can be used successfully to treat disease. However, real-time biomarkers of efficacy of this treatment are not available.
Here, the study will develop a framework to decode a multitude of noninvasive physiological signals during controlled autonomic testing to form a model that can quantify ANS balance, as well as the effects of taVNS on the system, in healthy and able-bodied individuals. Data derived from this study will enable the ability to detect early and significant deviations from "normal" homeostasis and provide novel non-invasive real-time biomarkers that could be used to assess disease onset or severity, as well as efficacy of a therapy in activating the ANS in a specific way. In the long-term, this will improve current treatment protocols and suggest new therapeutic opportunities.
- Conditions
- Autonomic Dysfunction, Autonomic Imbalance, Autonomic Nervous System Diseases, Vagus Nerve Autonomic Disorder
- Being tested
- Standing-Squatting-Standing Test, Deep Breathing Test, Cold Pressor Test, Cold Face Test, Valsalva Maneuver
- Keywords
- Vagus Nerve Stimulation, Noninvasive, Autonomic Nervous System, Biosensors, Vitals Monitoring, Machine Learning, Deep Learning
- Medical subject headings
- Primary Dysautonomias, Autonomic Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standing-Squatting-Standing TestOther
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.
Deep Breathing TestOther
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.
Cold Pressor TestOther
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.
Cold Face TestOther
Also called Diving Reflex Text
The cold stimulus will be applied with refrigerated gel-filled compresses places on the forehead and cheeks of the participant for one minute.
Valsalva ManeuverOther
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.
Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)Device
Also called Noninvasive Vagus Nerve Stimulation at the Ear
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.
| Study group | Role | What they receive |
|---|---|---|
| Healthy, Able-Bodied Individuals | This study will only enroll healthy, able-bodied individuals. Receives: 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Heart Rate (Electrocardiography) related to Autonomic Nervous System Perturbations
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).
Measured: 4 2-hour sessions over 2 weeks
Changes in Brain Activity (Electroencephalography) related to Autonomic Nervous System Perturbations
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).
Measured: 4 2-hour sessions over 2 weeks
Changes in Respiratory Rate related to Autonomic Nervous System Perturbations
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 expiration (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).
Measured: 4 2-hour sessions over 2 weeks
Changes in Sweat Gland Activity (Galvanic Skin Response) related to Autonomic Nervous System Perturbations
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).
Measured: 4 2-hour sessions over 2 weeks
Changes in Blood Pressure related to Autonomic Nervous System Perturbations
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).
Measured: 4 2-hour sessions over 2 weeks
Changes in Skin Temperature related to Autonomic Nervous System Perturbations
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).
Measured: 4 2-hour sessions over 2 weeks
Changes in Pupil Size related to Autonomic Nervous System Perturbations
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).
Measured: 4 2-hour sessions over 2 weeks
Secondary outcomes (7)
Changes in Heart Rate (Electrocardiography) due to taVNS
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).
Measured: 4 2-hour sessions over 2 weeks
Changes in Brain Activity (Electroencephalography) due to taVNS
Power in EEG frequency bands will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).
Measured: 4 2-hour sessions over 2 weeks
Changes in Respiratory Rate due to taVNS
Respiratory rates will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).
Measured: 4 2-hour sessions over 2 weeks
Changes in Sweat Gland Activity (Galvanic Skin Response) due to taVNS
GSR will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).
Measured: 4 2-hour sessions over 2 weeks
Changes in Blood Pressure due to taVNS
Blood pressure will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).
Measured: 4 2-hour sessions over 2 weeks
Changes in Skin Temperature due to taVNS
Skin temperature will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).
Measured: 4 2-hour sessions over 2 weeks
Changes in Pupil Size due to taVNS
Pupil size will be assessed as percent change during taVNS, with a comparison to baseline (before and after stimulation).
Measured: 4 2-hour sessions over 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2019
- Study start29 Aug 2019
- Primary completionJul 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (43)Papers the sponsor has linked to this study.
- Other trials for Autonomic DysfunctionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Theodoros Zanos, Northwell Health
- Investigators
- Theodoros P Zanos, PhD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04100486
- Sponsor's protocol ID
- 19-0461
- Acronym
- NIBA
- Status last verified
- Jun 2026
- First submitted
- 16 Sep 2019
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Addorisio ME, Imperato GH, de Vos AF, Forti S, Goldstein RS, Pavlov VA, van der Poll T, Yang H, Diamond B, Tracey KJ, Chavan SS. Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear. Bioelectron Med. 2019 Apr 17;5:4. doi: 10.1186/s42234-019-0020-4. eCollection 2019.
PubMed 32232095Andersson U, Tracey KJ. Neural reflexes in inflammation and immunity. J Exp Med. 2012 Jun 4;209(6):1057-68. doi: 10.1084/jem.20120571.
PubMed 22665702Badke CM, Marsillio LE, Weese-Mayer DE, Sanchez-Pinto LN. Autonomic Nervous System Dysfunction in Pediatric Sepsis. Front Pediatr. 2018 Oct 9;6:280. doi: 10.3389/fped.2018.00280. eCollection 2018.
PubMed 30356758Badran BW, Mithoefer OJ, Summer CE, LaBate NT, Glusman CE, Badran AW, DeVries WH, Summers PM, Austelle CW, McTeague LM, Borckardt JJ, George MS. Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate. Brain Stimul. 2018 Jul-Aug;11(4):699-708. doi: 10.1016/j.brs.2018.04.004. Epub 2018 Apr 6.
PubMed 29716843Bonaz B, Sinniger V, Hoffmann D, Clarencon D, Mathieu N, Dantzer C, Vercueil L, Picq C, Trocme C, Faure P, Cracowski JL, Pellissier S. Chronic vagus nerve stimulation in Crohn's disease: a 6-month follow-up pilot study. Neurogastroenterol Motil. 2016 Jun;28(6):948-53. doi: 10.1111/nmo.12792. Epub 2016 Feb 27.
PubMed 26920654Carthy ER. Autonomic dysfunction in essential hypertension: A systematic review. Ann Med Surg (Lond). 2013 Dec 11;3(1):2-7. doi: 10.1016/j.amsu.2013.11.002. eCollection 2014 Mar.
PubMed 25568776Chavan SS, Pavlov VA, Tracey KJ. Mechanisms and Therapeutic Relevance of Neuro-immune Communication. Immunity. 2017 Jun 20;46(6):927-942. doi: 10.1016/j.immuni.2017.06.008.
PubMed 28636960Coote JH, Chauhan RA. The sympathetic innervation of the heart: Important new insights. Auton Neurosci. 2016 Aug;199:17-23. doi: 10.1016/j.autneu.2016.08.014. Epub 2016 Aug 24.
PubMed 27568995Costa J, Moreira A, Moreira P, Delgado L, Silva D. Effects of weight changes in the autonomic nervous system: A systematic review and meta-analysis. Clin Nutr. 2019 Feb;38(1):110-126. doi: 10.1016/j.clnu.2018.01.006. Epub 2018 Jan 9.
PubMed 29395374Engel T, Ben-Horin S, Beer-Gabel M. Autonomic Dysfunction Correlates with Clinical and Inflammatory Activity in Patients with Crohn's Disease. Inflamm Bowel Dis. 2015 Oct;21(10):2320-6. doi: 10.1097/MIB.0000000000000508.
PubMed 26181429Ferreira JA, Bissell BD. Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock. J Intensive Care Med. 2018 Feb;33(2):74-86. doi: 10.1177/0885066616689548. Epub 2017 Jan 31.
PubMed 28142307Freeman R, Chapleau MW. Testing the autonomic nervous system. Handb Clin Neurol. 2013;115:115-36. doi: 10.1016/B978-0-444-52902-2.00007-2.
PubMed 23931777Gibbons, 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
Hilz MJ, Stemper B, Sauer P, Haertl U, Singer W, Axelrod FB. Cold face test demonstrates parasympathetic cardiac dysfunction in familial dysautonomia. Am J Physiol. 1999 Jun;276(6):R1833-9. doi: 10.1152/ajpregu.1999.276.6.R1833.
PubMed 10362767Huang F, Dong J, Kong J, Wang H, Meng H, Spaeth RB, Camhi S, Liao X, Li X, Zhai X, Li S, Zhu B, Rong P. Erratum to: Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study. BMC Complement Altern Med. 2016 Jul 13;16(1):218. doi: 10.1186/s12906-016-1190-1. No abstract available.
PubMed 27411374
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Quantify the Autonomic Nervous System Balance in Healthy, Able-Bodied Individuals
- ClinicalTrials.gov ID
- NCT04100486
- Acronym / sponsor ID
- NIBA / 19-0461
- Conditions
- Autonomic Dysfunction, Autonomic Imbalance, Autonomic Nervous System Diseases, Vagus Nerve Autonomic Disorder
- Keywords
- Vagus Nerve Stimulation, Noninvasive, Autonomic Nervous System, Biosensors, Vitals Monitoring, Machine Learning, Deep Learning
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 29 Aug 2019 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 24 Sep 2019 (actual)
- 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.
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.
Detailed description
Biomarkers that reflect disease presence or intensity, or treatment efficacy are central to medical advancements. Recorded biomarkers provide information about physiological processes regulated by the autonomic nervous system (ANS), which include blood pressure, heart rate, sweating, and body temperature. The ANS has two major divisions: sympathetic and parasympathetic systems. Most organs receive reciprocal input from both systems to achieve homeostasis through ANS balance. This regulation occurs without conscious control (i.e., autonomously). Dysregulation of the ANS can occur as the result of disorders or injuries, including diabetes, sepsis, spinal cord injuries (SCI), Parkinson's disease, and many other conditions.
The ANS is the part of the nervous system that regulates and integrates bodily functions that typically run involuntary, particularly internal organs including blood vessels, lungs, pupils, heart, sweat, and salivary glands. Along with immunological systems, it controls and adapts homeostasis of the internal environment based on changes in the external environment. Disturbances in autonomic regulation have been described in a variety of diseases and disorders, including those that directly affect the nervous system, such as spinal cord injuries and stroke, and those that afflict other organ systems, such as sepsis and infection, rheumatoid arthritis, Crohn's disease, diabetes mellitus, and numerous heart conditions. This dysregulation manifests differently for each of these conditions, even inconsistently across patients, and the significance of symptoms due to ANS dysfunction are not well understood.
The ANS can be divided into two major branches: the sympathetic and parasympathetic systems. All internal organs are innervated by one or both component systems through the ANS main conduits, which include the brainstem, spinal cord, and cranial nerves, such as the vagus nerve. The branches typically function opposite and complementary of each other; physiological changes associated with the sympathetic system include accelerating heart rate, dilating pupils, and perspiration, while the parasympathetic system slows the heart, lowers blood pressure, and relaxes muscles. Both systems work in tandem to modulate and maintain blood pressure, vagal tone, heart rate, respiration, and cardiac contractility. While both systems operate to maintain homeostasis, the sympathetic system can be considered a quick response and mobilizing system, while the parasympathetic is a more slowly activated and dampening system.
Instead of measuring the ANS directly from the central or peripheral nervous system through invasive implants, it is possible to record physiological signals through advances in noninvasive clinical testing. Laboratories are able to test autonomic function and rely on batteries of accepted, noninvasive tests. According to the American Academy of Neurology (AAN), standard techniques of autonomic testing include measuring heart rate and blood pressure variability during deep breathing, tilt table, and the Valsalva maneuver to assess cardiovagal (parasympathetic) and sudomotor (sympathetic) function. It is straightforward to add to the limited necessary equipment (blood pressure cuff, electrocardiogram [ECG]) by including electroencephalography (EEG) to measure brain activity, electromyography (EMG) to measure muscle activity, and eye tracking glasses to measure pupillometry during this battery. All noninvasive signals can be measured during controlled perturbations to characterize the ANS. Assessment of ANS function is now used in multiple disciplines, including neurology, cardiology, psychology, psychophysiology, obstetrics, anesthesiology, and psychiatry.
Neural reflexes control responses in the cardiovascular, pulmonary, gastrointestinal, renal, hepatic, and endocrine systems. The vagus nerve-based inflammatory reflex is of particularly interest at the Feinstein Institute for Medical Research and has been shown to regulate immune function. The nervous system interacts with the immune system by this pathway; molecular mediators of innate immunity activate afferent signals in the vagus nerve to the brainstem, which sends efferent signals down the vagus nerve to regulate inflammation and cytokine release. Vagus nerve stimulation (VNS) has been shown to decrease production and release of pro-inflammatory cytokines; bioelectronic devices have been used in preclinical and pilot clinical trials to reduce inflammation in patients with rheumatoid arthritis and Crohn's disease.
The auricular branch of the vagus nerve comes from the vagus and innervates cutaneous areas of the outer ear. Transcutaneous auricular vagus nerve stimulation (taVNS) offers a non-invasive means of stimulating the vagus nerve without surgical intervention. The device consists of a clip that supplies electrical signals to processes of the auricle, and it has been used in previous clinical studies for multiple conditions, including refractory epilepsy, depression, pre-diabetes, tinnitus, memory, stroke, oromotor dysfunction, and rheumatoid arthritis, with additional studies planned for therapy or treatment of stroke, atrial fibrillation, and heart failure. These studies have used a range of electrical stimulation settings and sites; the mechanism of taVNS and responses are not well understood, as well as the effects of changes in stimulation parameters on ANS.
Recently, application of machine learning models and decoding algorithms permits utilizing commonly used clinical measurement of physiological signals to better understand broader phenomena of autonomic function and dysregulation. Research has been focused on developing quantitative standards based on biomarkers to aid with diagnosis, prognosis, and estimates of treatment efficacy. Autonomic data could potentially capture objective measures of disease states, and machine learning techniques can be used to extract relevant features towards building a predictive model of ANS balance. By training such a model on recordings from healthy, able-bodied individuals, the investigators plan to characterize ANS balance, and then apply this model to new data sets and individuals to diagnose or predict disease states.
Modern methods of computational science have been used to decode complex clinical and experimental data by detecting patterns, classifying signals, and extracting information towards new knowledge. Through signal processing techniques, it has been possible to decode autonomic nervous system signals conveyed through the vagus nerve by identifying groups of vagal neurons that fire in response to the administration of specific cytokines. Additionally, machine learning has been used to quantify clinical pain using multimodal autonomic metrics and neuroimaging, and large-scale ambulatory data has been used to monitor physiological signals and develop multi-sensor models to detect stress in daily life.
Additionally, the investigators want to examine how these measurements are affected by the use of non-invasive transcutaneous electrical stimulation of the vagus nerve. Stimulation of the vagus nerve by a surgically implanted stimulator regulates and suppresses pro-inflammatory cytokine release. This has now been used in a successful clinical trial to treat rheumatoid arthritis and Crohn's disease. Non-invasive transcutaneous stimulation of the vagus nerve has also been showing promising early results, indicating that non-invasive methods of activating a specific part of the autonomic nervous system can be used successfully to treat disease. However, real-time biomarkers of efficacy of this treatment are not available.
Here, the study will develop a framework to decode a multitude of noninvasive physiological signals during controlled autonomic testing to form a model that can quantify ANS balance, as well as the effects of taVNS on the system, in healthy and able-bodied individuals. Data derived from this study will enable the ability to detect early and significant deviations from "normal" homeostasis and provide novel non-invasive real-time biomarkers that could be used to assess disease onset or severity, as well as efficacy of a therapy in activating the ANS in a specific way. In the long-term, this will improve current treatment protocols and suggest new therapeutic opportunities.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy, Able-Bodied Individuals | – | 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)This study will only enroll healthy, able-bodied individuals. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
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 |
|---|---|---|
| Standing-Squatting-Standing TestThe 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 | Healthy, Able-Bodied Individuals |
| Deep Breathing TestThe 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 | Healthy, Able-Bodied Individuals |
| Cold Pressor TestThe 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 | Healthy, Able-Bodied Individuals |
| Cold Face TestAlso: Diving Reflex TextThe cold stimulus will be applied with refrigerated gel-filled compresses places on the forehead and cheeks of the participant for one minute. | Other | Healthy, Able-Bodied Individuals |
| Valsalva ManeuverThe 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. | Other | Healthy, Able-Bodied Individuals |
| Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)Also: Noninvasive Vagus Nerve Stimulation at the EarThe 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. | Device | Healthy, Able-Bodied Individuals |
Primary outcome
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).
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).
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 expiration (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).
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).
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).
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).
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).
7 secondary outcomes
Changes in Heart Rate (Electrocardiography) due to taVNS
Time frame: 4 2-hour sessions over 2 weeks
Changes in Brain Activity (Electroencephalography) due to taVNS
Time frame: 4 2-hour sessions over 2 weeks
Changes in Respiratory Rate due to taVNS
Time frame: 4 2-hour sessions over 2 weeks
Changes in Sweat Gland Activity (Galvanic Skin Response) due to taVNS
Time frame: 4 2-hour sessions over 2 weeks
Changes in Blood Pressure due to taVNS
Time frame: 4 2-hour sessions over 2 weeks
Changes in Skin Temperature due to taVNS
Time frame: 4 2-hour sessions over 2 weeks
Changes in Pupil Size due to taVNS
Time frame: 4 2-hour sessions over 2 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Background: PubMed 32232095Addorisio ME, Imperato GH, de Vos AF, Forti S, Goldstein RS, Pavlov VA, van der Poll T, Yang H, Diamond B, Tracey KJ, Chavan SS. Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear. Bioelectron Med. 2019 Apr 17;5:4. doi: 10.1186/s42234-019-0020-4. eCollection 2019.
- Background: PubMed 22665702Andersson U, Tracey KJ. Neural reflexes in inflammation and immunity. J Exp Med. 2012 Jun 4;209(6):1057-68. doi: 10.1084/jem.20120571.
- Background: PubMed 30356758Badke CM, Marsillio LE, Weese-Mayer DE, Sanchez-Pinto LN. Autonomic Nervous System Dysfunction in Pediatric Sepsis. Front Pediatr. 2018 Oct 9;6:280. doi: 10.3389/fped.2018.00280. eCollection 2018.
- Background: PubMed 29716843Badran BW, Mithoefer OJ, Summer CE, LaBate NT, Glusman CE, Badran AW, DeVries WH, Summers PM, Austelle CW, McTeague LM, Borckardt JJ, George MS. Short trains of transcutaneous auricular vagus nerve stimulation (taVNS) have parameter-specific effects on heart rate. Brain Stimul. 2018 Jul-Aug;11(4):699-708. doi: 10.1016/j.brs.2018.04.004. Epub 2018 Apr 6.
- Background: PubMed 26920654Bonaz B, Sinniger V, Hoffmann D, Clarencon D, Mathieu N, Dantzer C, Vercueil L, Picq C, Trocme C, Faure P, Cracowski JL, Pellissier S. Chronic vagus nerve stimulation in Crohn's disease: a 6-month follow-up pilot study. Neurogastroenterol Motil. 2016 Jun;28(6):948-53. doi: 10.1111/nmo.12792. Epub 2016 Feb 27.
- Background: PubMed 25568776Carthy ER. Autonomic dysfunction in essential hypertension: A systematic review. Ann Med Surg (Lond). 2013 Dec 11;3(1):2-7. doi: 10.1016/j.amsu.2013.11.002. eCollection 2014 Mar.
- Background: PubMed 28636960Chavan SS, Pavlov VA, Tracey KJ. Mechanisms and Therapeutic Relevance of Neuro-immune Communication. Immunity. 2017 Jun 20;46(6):927-942. doi: 10.1016/j.immuni.2017.06.008.
- Background: PubMed 27568995Coote JH, Chauhan RA. The sympathetic innervation of the heart: Important new insights. Auton Neurosci. 2016 Aug;199:17-23. doi: 10.1016/j.autneu.2016.08.014. Epub 2016 Aug 24.
- Background: PubMed 29395374Costa J, Moreira A, Moreira P, Delgado L, Silva D. Effects of weight changes in the autonomic nervous system: A systematic review and meta-analysis. Clin Nutr. 2019 Feb;38(1):110-126. doi: 10.1016/j.clnu.2018.01.006. Epub 2018 Jan 9.
- Background: PubMed 26181429Engel T, Ben-Horin S, Beer-Gabel M. Autonomic Dysfunction Correlates with Clinical and Inflammatory Activity in Patients with Crohn's Disease. Inflamm Bowel Dis. 2015 Oct;21(10):2320-6. doi: 10.1097/MIB.0000000000000508.
- Background: PubMed 28142307Ferreira JA, Bissell BD. Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock. J Intensive Care Med. 2018 Feb;33(2):74-86. doi: 10.1177/0885066616689548. Epub 2017 Jan 31.
- Background: PubMed 23931777Freeman R, Chapleau MW. Testing the autonomic nervous system. Handb Clin Neurol. 2013;115:115-36. doi: 10.1016/B978-0-444-52902-2.00007-2.
- Individual participant dataSharing planned: No
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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.
Theodoros P Zanos, PhD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Autonomic Dysfunction and Autonomic Imbalance, run by Northwell Health 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 5 inclusion and 13 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: enrolling by invitation, as of the sponsor's last update on 9 Jun 2026. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Changes in Heart Rate (Electrocardiography) related to Autonomic Nervous System Perturbations (time frame: 4 2-hour sessions over 2 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04100486, which also lists 43 linked publications.
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 9 Jun 2026.