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Mechanisms of Vasovagal Syncope

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by New York Medical College
Sponsor:
Information provided by (Responsible Party):
Julian Stewart, New York Medical College
ClinicalTrials.gov Identifier:
NCT01791816
First received: February 12, 2013
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Vasovagal Syncope
Postural Tachycardia Syndrome
Drug: Phenylephrine
Drug: L-Ng-monomethyl Arginine (L-NMMA)
Phase 0

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Mechanisms of Vasovagal Syncope

Resource links provided by NLM:


Further study details as provided by New York Medical College:

Primary Outcome Measures:
  • Heart rate and blood pressure in response to Lower Body Negative Pressure(LBNP) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: February 2013
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   14 Years to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01791816

Contacts
Contact: Courtney R Terilli, RN, BSN 914-593-8888 courtney_terilli@nymc.edu
Contact: Julian M. Stewart, M.D., Ph.D. 914-593-8888 julian_stewart@nymc.edu

Locations
United States, New York
New York Medical College/Bradhurst Building Recruiting
Hawthorne, New York, United States, 10532
Contact: Courtney R. Terilli, RN, BSN    914-593-8888    courtney_terilli@nymc.edu   
Contact: Julian M. Stewart, M.D., Ph. D.    914-593-8888    julian_stewart@nymc.edu   
Principal Investigator: Julian M. Stewart, M.D., Ph.D.         
Sub-Investigator: Marvin M. Medow, Ph.D.         
Sponsors and Collaborators
New York Medical College
Investigators
Principal Investigator: Julian M. Stewart, M.D., Ph.D. New York Medical College
  More Information

Additional Information:
No publications provided

Responsible Party: Julian Stewart, Professor of Pediatrics, New York Medical College
ClinicalTrials.gov Identifier: NCT01791816     History of Changes
Other Study ID Numbers: 1R01HL112736-01A1
Study First Received: February 12, 2013
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by New York Medical College:
Vasovagal Syncope
Postural Tachycardia Syndrome
Orthostatic Intolerance
Nitric Oxide (NO)
Orthostatic Stress
L-Ng-monomethyl Arginine (L-NMMA)
Phenylephrine
Sodium Nitroprusside

Additional relevant MeSH terms:
Syncope
Syncope, Vasovagal
Postural Orthostatic Tachycardia Syndrome
Syndrome
Tachycardia
Arrhythmias, Cardiac
Autonomic Nervous System Diseases
Cardiovascular Diseases
Consciousness Disorders
Disease
Heart Diseases
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Orthostatic Intolerance
Pathologic Processes
Primary Dysautonomias
Signs and Symptoms
Unconsciousness
Omega-N-Methylarginine
Oxymetazoline
Phenylephrine
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Autonomic Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014