Clinical trial NCT01791816: Mechanisms of Vasovagal Syncope
Official title: Mechanisms of Vasovagal Syncope
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: 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
Lead sponsor: New York Medical College
Sponsor class: OTHER
First posted: 2013-02-15
Enrollment: 90
Sex: ALL
Minimum age (years): 14
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility 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.

Primary outcomes:
measure: Heart rate and blood pressure in response to Lower Body Negative Pressure(LBNP)
timeFrame: 1 year
Secondary outcomes:
measure: Adrenergic neurotransmission as measured by Muscle Sympathetic Nerve Activity(MSNA), doppler ultrasound blood flow, venous Norepinephrine in response to Phenylephrine infusion
timeFrame: 1 year
Other outcomes:
Locations:
city: Hawthorne
country: United States
facility: New York Medical College/Bradhurst Building
state: New York
Study officials:
affiliation: New York Medical College
name: Julian M. Stewart, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: