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Mechanisms of Vasovagal Syncope

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. Read our disclaimer for details. Identifier: NCT01791816
Recruitment Status : Active, not recruiting
First Posted : February 15, 2013
Last Update Posted : February 25, 2021
Information provided by (Responsible Party):
Julian Stewart, New York Medical College

Brief Summary:
Vasovagal Syncope (simple postural faint) is the most common cause of acute loss of consciousness. Postural tachycardia syndrome(POTS) is the most common chronic form of postural lightheadedness. Together they afflict many Americans, mostly young women, who are prevented from gainful employ or school attendance. The underlying mechanism is not known. Our past work suggests that a simple molecule, nitric oxide, acts to subvert normal blood flow controls causing blood to pool in the gut when standing. Our proposal will show the mechanism behind this problem and will indicate effective medical treatments. Patients will be compared to healthy control subjects.

Condition or disease Intervention/treatment Phase
Vasovagal Syncope Postural Tachycardia Syndrome Drug: Phenylephrine Drug: L-Ng-monomethyl Arginine (L-NMMA) Early Phase 1

Detailed Description:
Vasovagal Syncope (VVS,simple faint) is the most common cause of transient loss of consciousness and is the acute episodic form of orthostatic intolerance(OI). Postural tachycardia syndrome (POTS) is the common chronic form of OI. Both are defined by debilitating symptoms and signs while upright relieved by recumbency. Pathophysiological mechanisms have remained elusive although our past work shows that excessive upright central hypovolemia results from splanchnic pooling due to defective splanchnic arterial and venous constriction. Preliminary data support the hypothesis that production of nitric oxide (NO) is enhanced in these patients resulting in reduced sympathetic noradrenergic neurotransmission at pre-junctional and post-junctional sites. Our approach is two-fold: 1) We will use intradermal microdialysis and laser Doppler flowmetry (LDF) to delineate the microvascular mechanisms of NO modulation of noradrenergic neurotransmission free of confounding systemic reflex changes. 2) We will systemically apply this mechanism to a model of orthostatic stress, lower body negative pressure(LBNP), while measuring cardiac output by inert gas rebreathing, regional blood volume, and regional blood flow using plethysmographic techniques focusing on splanchnic changes, and muscle sympathetic nerve activity by peroneal microneurography. We will study synaptic peripheral neurotransmission of Norepinephrine and how it is affected by supplemental NO and by nitric oxide synthase inhibitor.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Mechanisms of Vasovagal Syncope
Study Start Date : February 2013
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fainting

Arm Intervention/treatment
Experimental: Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA) Drug: Phenylephrine

Phenylephrine dose-response comprises infusion of 0.5, 1, 2, 3, 4 micrograms/kg/min for 10 min at each dose.

If bloods pressure increases by 30% or if heart rate decreases below 40 beats per minute we will stop infusion.

Drug: L-Ng-monomethyl Arginine (L-NMMA)
Systemic L-NMMA is infused as a 500μg/kg/min loading dose for 15 min followed by a 50μg/kg/min maintenance dose for the remainder of the experiment.

Primary Outcome Measures :
  1. Heart rate and blood pressure in response to Lower Body Negative Pressure(LBNP) [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. Adrenergic neurotransmission as measured by Muscle Sympathetic Nerve Activity(MSNA), doppler ultrasound blood flow, venous Norepinephrine in response to Phenylephrine infusion [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. POTS patients referred for day to day orthostatic intolerance with greater than 3 symptoms for greater than 3 months and will have the diagnosis of symptomatic postural tachycardia made during a screening tilt table test :

    • dizziness
    • nausea and vomiting
    • palpitations
    • fatigue
    • headache
    • exercise intolerance
    • blurred vision
    • abnormal sweating heat.
  2. Vasovagal Syncope patients will have at least 3 episodes of fainting episodes in the past year.
  3. Healthy control subjects

Cases will be between the ages of 14 and 29 years old Cases will have normal physical examination, and normal electrocardiographic and echocardiographic evaluations.

Only those free from heart disease, and from systemic illness will be eligible to participate.

This excludes patients with illnesses and disease states known to be associated with endothelial cell dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, morbid obesity and peripheral vascular disease.

At the time of testing all patients and control subjects must refrain from vasoactive drugs for two weeks. Please check with us about any medication that you are taking.

Exclusion Criteria:

  • Cardiovascular causes of syncope
  • An active medical condition that may explain the diagnosis
  • A previous medical condition with undocumented resolution that may explain the diagnosis
  • Past or present major psychiatric disorder
  • Substance abuse within 2 years before onset of symptoms.

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 identifier (NCT number): NCT01791816

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United States, New York
New York Medical College/Bradhurst Building
Hawthorne, New York, United States, 10532
Sponsors and Collaborators
New York Medical College
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Principal Investigator: Julian M. Stewart, M.D., Ph.D. New York Medical College
Additional Information:
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Responsible Party: Julian Stewart, Professor of Pediatrics, New York Medical College Identifier: NCT01791816    
Other Study ID Numbers: 1R01HL112736-01A1 ( U.S. NIH Grant/Contract )
First Posted: February 15, 2013    Key Record Dates
Last Update Posted: February 25, 2021
Last Verified: February 2021
Keywords provided by Julian Stewart, New York Medical College:
Vasovagal Syncope
Postural Tachycardia Syndrome
Orthostatic Intolerance
Nitric Oxide (NO)
Orthostatic Stress
L-Ng-monomethyl Arginine (L-NMMA)
Sodium Nitroprusside
Additional relevant MeSH terms:
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Postural Orthostatic Tachycardia Syndrome
Syncope, Vasovagal
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Cardiotonic Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Vasoconstrictor Agents
Nasal Decongestants
Respiratory System Agents
Adrenergic alpha-1 Receptor Agonists