Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
ENROLLING_BY_INVITATION
Total Enrollment
48 participants
Study Classification
OBSERVATIONAL
Study Start Date
2019-08-29
Study Completion Date
2025-09-30
Brief Summary
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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.
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Detailed Description
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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.
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
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Autonomic Dysfunction
Autonomic Imbalance
Autonomic Nervous System Diseases
Vagus Nerve Autonomic Disorder
Study Design
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Observational Model Type
OTHER
Study Time Perspective
PROSPECTIVE
Study Groups
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Healthy, Able-Bodied Individuals
This study will only enroll healthy, able-bodied individuals.
Standing-Squatting-Standing Test
Intervention Type
OTHER
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 Test
Intervention Type
OTHER
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 Test
Intervention Type
OTHER
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 Test
Intervention Type
OTHER
The cold stimulus will be applied with refrigerated gel-filled compresses places on the forehead and cheeks of the participant for one minute.
Valsalva Maneuver
Intervention Type
OTHER
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)
Intervention Type
DEVICE
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.
Interventions
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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.
Intervention Type
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.
Intervention Type
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.
Intervention Type
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.
Intervention Type
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.
Intervention Type
OTHER
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.
Intervention Type
DEVICE
Other Intervention Names
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Diving Reflex Text
Noninvasive Vagus Nerve Stimulation at the Ear
Eligibility Criteria
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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
* 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
* 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
Minimum Eligible Age
18 Years
Maximum Eligible Age
60 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
Yes
Sponsors
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Northwell Health
OTHER
Sponsor Role
lead
Responsible Party
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Theodoros Zanos
Assistant Professor, Neural and Data Science Laboratory
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
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Theodoros P Zanos, PhD
Role: PRINCIPAL_INVESTIGATOR
Northwell Health
Locations
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The Feinstein Institutes for Medical Research
Manhasset, New York, United States
Site Status
Countries
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United States
References
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Engel 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.
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Huang 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.
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Kishi T. Heart failure as an autonomic nervous system dysfunction. J Cardiol. 2012 Mar;59(2):117-22. doi: 10.1016/j.jjcc.2011.12.006. Epub 2012 Feb 16.
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Kong J, Fang J, Park J, Li S, Rong P. Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives. Front Psychiatry. 2018 Feb 5;9:20. doi: 10.3389/fpsyt.2018.00020. eCollection 2018.
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Badran 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.
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Bonaz 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.
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Carthy 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.
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Chavan 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.
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Coote 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.
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Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8284-9. doi: 10.1073/pnas.1605635113. Epub 2016 Jul 5.
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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
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Broadstone VL, Roy T, Self M, Pfeifer MA. Cardiovascular autonomic dysfunction: diagnosis and prognosis. Diabet Med. 1991;8 Spec No:S88-93. doi: 10.1111/j.1464-5491.1991.tb02165.x.
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Lee J, Mawla I, Kim J, Loggia ML, Ortiz A, Jung C, Chan ST, Gerber J, Schmithorst VJ, Edwards RR, Wasan AD, Berna C, Kong J, Kaptchuk TJ, Gollub RL, Rosen BR, Napadow V. Machine learning-based prediction of clinical pain using multimodal neuroimaging and autonomic metrics. Pain. 2019 Mar;160(3):550-560. doi: 10.1097/j.pain.0000000000001417.
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Levine YA, Koopman FA, Faltys M, Caravaca A, Bendele A, Zitnik R, Vervoordeldonk MJ, Tak PP. Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis. PLoS One. 2014 Aug 11;9(8):e104530. doi: 10.1371/journal.pone.0104530. eCollection 2014.
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DERIVED
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
19-0461
Identifier Type: -
Identifier Source: org_study_id
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