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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)

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:

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.

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

NCT ID

NCT01791816

First Posted

February 12, 2013

Last Updated

April 5, 2022

Sponsor

New York Medical College

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

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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