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Mechanisms of Vasovagal Syncope

Primary Purpose

Vasovagal Syncope, Postural Tachycardia Syndrome

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Phenylephrine
L-Ng-monomethyl Arginine (L-NMMA)
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Vasovagal Syncope focused on measuring Vasovagal Syncope, Postural Tachycardia Syndrome, Orthostatic Intolerance, Nitric Oxide (NO), Orthostatic Stress, L-Ng-monomethyl Arginine (L-NMMA), Phenylephrine, Sodium Nitroprusside

Eligibility Criteria

14 Years - 29 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • New York Medical College/Bradhurst Building

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA)

Arm Description

Outcomes

Primary Outcome Measures

Heart rate and blood pressure in response to Lower Body Negative Pressure(LBNP)

Secondary Outcome Measures

Adrenergic neurotransmission as measured by Muscle Sympathetic Nerve Activity(MSNA), doppler ultrasound blood flow, venous Norepinephrine in response to Phenylephrine infusion

Full Information

First Posted
February 12, 2013
Last Updated
April 5, 2022
Sponsor
New York Medical College
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1. Study Identification

Unique Protocol Identification Number
NCT01791816
Brief Title
Mechanisms of Vasovagal Syncope
Official Title
Mechanisms of Vasovagal Syncope
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2013 (undefined)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vasovagal Syncope, Postural Tachycardia Syndrome
Keywords
Vasovagal Syncope, Postural Tachycardia Syndrome, Orthostatic Intolerance, Nitric Oxide (NO), Orthostatic Stress, L-Ng-monomethyl Arginine (L-NMMA), Phenylephrine, Sodium Nitroprusside

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Phenylephrine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
L-Ng-monomethyl Arginine (L-NMMA)
Intervention Description
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 Measure Information:
Title
Heart rate and blood pressure in response to Lower Body Negative Pressure(LBNP)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
29 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Vasovagal Syncope patients will have at least 3 episodes of fainting episodes in the past year. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julian M. Stewart, M.D., Ph.D.
Organizational Affiliation
New York Medical College
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York Medical College/Bradhurst Building
City
Hawthorne
State/Province
New York
ZIP/Postal Code
10532
Country
United States

12. IPD Sharing Statement

Links:
URL
http://syncope.org/
Description
The Center for Hypotension

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Mechanisms of Vasovagal Syncope

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