Vasovagal SyncopeEarly Phase 1NCT01791816
Mechanisms of Vasovagal Syncope
A Early Phase 1 study testing Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA) in people with Vasovagal Syncope and Postural Tachycardia Syndrome, run by New York Medical College at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 14 to 29 yearsHealthy volunteers can take part
- Conditions the study is for
- Vasovagal Syncope, Postural Tachycardia Syndrome
- What is being tested?
- Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Dec 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 29 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Show all 15Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York Medical College/Bradhurst Building
Hawthorne, New York, 10532
About this study
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.
Read the 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.
- Conditions
- Vasovagal Syncope, Postural Tachycardia Syndrome
- Being tested
- Phenylephrine, L-Ng-monomethyl Arginine (L-NMMA)
- Keywords
- Vasovagal Syncope, Postural Tachycardia Syndrome, Orthostatic Intolerance, Nitric Oxide (NO), Orthostatic Stress, L-Ng-monomethyl Arginine (L-NMMA), Phenylephrine, Sodium Nitroprusside
- Medical subject headings
- Syncope, Vasovagal, Postural Orthostatic Tachycardia Syndrome, Orthostatic Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenylephrineDrug
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA) | Experimental | Not described Receives: Drug: Phenylephrine; Drug: L-Ng-monomethyl Arginine (L-NMMA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate and blood pressure in response to Lower Body Negative Pressure(LBNP)
Measured: 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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionDec 2022
- Study completionDec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vasovagal SyncopeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York Medical College
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Julian Stewart, New York Medical College
- Investigators
- Julian M. Stewart, M.D., Ph.D., Principal investigator, New York Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01791816
- Sponsor's protocol ID
- 1R01HL112736-01A1
- Status last verified
- May 2025
- First submitted
- 12 Feb 2013
- Last updated
- 23 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Vasovagal Syncope
- ClinicalTrials.gov ID
- NCT01791816
- Acronym / sponsor ID
- 1R01HL112736-01A1
- 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
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- New York Medical CollegeUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Dec 2022 (actual)
- Study completion
- Dec 2022 (actual)
- First posted
- 15 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA) | Experimental | Drug: Phenylephrine, Drug: L-Ng-monomethyl Arginine (L-NMMA) |
Who may qualify
- Ages
- 14 to 29 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- 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 :
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PhenylephrinePhenylephrine 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 | Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA) |
| 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. | Drug | Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA) |
Primary outcome
Heart rate and blood pressure in response to Lower Body Negative Pressure(LBNP)
Time frame: 1 year
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julian M. Stewart, M.D., Ph.D. principal investigator
New York Medical College
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Phenylephrine and L-Ng-monomethyl Arginine (L-NMMA) in people with Vasovagal Syncope and Postural Tachycardia Syndrome, run by New York Medical College at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart rate and blood pressure in response to Lower Body Negative Pressure(LBNP) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2025.