Mechanisms of Vasovagal Syncope

NCT01791816 | Completed Early Phase 1 DMC

• 1 other identifier: 1R01HL112736-01A1
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

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

  1 year

Secondary Outcomes (1)

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

  1 year

Study Arms (1)

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

EXPERIMENTAL

Drug: Phenylephrine; Drug: L-Ng-monomethyl Arginine (L-NMMA)

Interventions

Phenylephrine DRUG

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.

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

L-Ng-monomethyl Arginine (L-NMMA) DRUG

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.

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

Eligibility Criteria

• Age: 14 Years - 29 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York Medical College: lead

Study Sites (1)

New York Medical College/Bradhurst Building

Hawthorne, New York, 10532, United States

Location

Related Links

• The Center for Hypotension

MeSH Terms

Conditions

Syncope, Vasovagal; Postural Orthostatic Tachycardia Syndrome; Orthostatic Intolerance

Interventions

Phenylephrine; omega-N-Methylarginine

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Syncope; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Julian M. Stewart, M.D., Ph.D.

  New York Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: February 12, 2013
• First Posted: February 15, 2013
• Study Start: February 1, 2013
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

US (1)