Northera Improves Postural Tachycardia Syndrome (POTS) and Postural Vasovagal Syncope (VVS)

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-30

Study Completion Date

2022-12-31

Brief Summary

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Vasovagal syncope (VVS, simple faint) is the most common cause of transient loss of consciousness and represents 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. Northera should therefore improve both sympathetic splanchnic arterial vasoconstriction and sympathetic splanchnic venoconstriction in POTS and VVS, and may represent an ideal drug to improve the orthostatic response in POTS and VVS.

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Detailed Description

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Vasovagal syncope (VVS, simple faint) is the most common cause of transient loss of consciousness and represents 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. Most POTS patients and all VVS patients have normal supine resting hemodynamics but excessively redistribute blood flow and blood volume from the central pool to the splanchnic vasculature because of defective splanchnic arterial vasoconstriction and venoconstriction. While peripheral and splanchnic arterial vasoconstriction depend primarily on post-junctional alpha-1 adrenergic receptors, splanchnic venoconstriction also depends on post-junctional alpha-2 adrenergic receptors. Consequently, selective alpha-1 agonists such as midodrine may not produce sufficient splanchnic venoconstriction to compensate for splanchnic pooling in POTS and VVS. Such alpha adrenergic subtype restrictions do not apply to Northera (droxidopa) because it is a norepinephrine (NE) prodrug and therefore increases the amount of synaptic NE that can then bind to both alpha-2 and alpha-1 receptors. Northera should therefore improve both sympathetic splanchnic arterial vasoconstriction and sympathetic splanchnic venoconstriction in POTS and VVS, and may represent an ideal drug to improve the orthostatic response in POTS and VVS. We will test the hypothesis that Northera, in appropriate dose, improves the splanchnic adrenergic deficits that initiate POTS and postural VVS and in sufficient daily dose improves quality of life in these patients. To accomplish this, the investigator will recruit 10 POTS patients aged 18-30 years, 10 similarly aged patients with 2 or more episodes of VVS in the past year (thus defining recurrent VVS) and 10 age and gender matched healthy volunteer control subjects with the following specific aims:

Conditions

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Postural Tachycardia Syndrome (POTS) Vasovagal Syncope (VVS) Fainting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Northera-single dose

Study #1 -Does single large dose (600mg) of Northera improve upright hemodynamics and orthostatic intolerance in POTS and VVS

Group Type PLACEBO_COMPARATOR

Northera (Droxidopa)

Intervention Type DRUG

Study #1 -Supine monitoring is performed for 30 minutes before administration of a single 600mg oral dose of Northera or placebo assigned randomly, After 2 hours supine a 70 degree upright tilt will performed for 10 minutes. On another day, subjects previously given Northera will receive placebo and vice versa and studies repeated.

Placebo

Intervention Type DRUG

Study #1 -Supine monitoring is performed for 30 minutes before administration of a single 600mg oral dose of Northera or placebo assigned randomly, After 2 hours supine a 70 degree upright tilt will performed for 10 minutes. On another day, subjects previously given Northera will receive placebo and vice versa and studies repeated.

Northera- chronic administration

Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day.

Group Type PLACEBO_COMPARATOR

Northera (Droxidopa)

Intervention Type DRUG

Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day. Doses will be reduced to the preceding dose if systolic BP\>140mmHg or diastolic BP\>80mmHg measured in the seated position at home using an automated ambulatory blood pressure cuff 2 hours after receiving an oral dose. Doses will also be reduced if supine BP measured with the head of the bed elevated upon awakening in the morning exceeds 150/90 mmHg. Following a 1 week wash out period, subjects will receive the alternative treatment for 2 additional weeks and instrumented laboratory studies repeated.

Placebo

Intervention Type DRUG

Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day. Doses will be reduced to the preceding dose if systolic BP\>140mmHg or diastolic BP\>80mmHg measured in the seated position at home using an automated ambulatory blood pressure cuff 2 hours after receiving an oral dose. Doses will also be reduced if supine BP measured with the head of the bed elevated upon awakening in the morning exceeds 150/90 mmHg. Following a 1 week wash out period, subjects will receive the alternative treatment for 2 additional weeks and instrumented laboratory studies repeated.

Interventions

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Northera (Droxidopa)

Study #1 -Supine monitoring is performed for 30 minutes before administration of a single 600mg oral dose of Northera or placebo assigned randomly, After 2 hours supine a 70 degree upright tilt will performed for 10 minutes. On another day, subjects previously given Northera will receive placebo and vice versa and studies repeated.

Intervention Type DRUG

Placebo

Study #1 -Supine monitoring is performed for 30 minutes before administration of a single 600mg oral dose of Northera or placebo assigned randomly, After 2 hours supine a 70 degree upright tilt will performed for 10 minutes. On another day, subjects previously given Northera will receive placebo and vice versa and studies repeated.

Intervention Type DRUG

Northera (Droxidopa)

Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day. Doses will be reduced to the preceding dose if systolic BP\>140mmHg or diastolic BP\>80mmHg measured in the seated position at home using an automated ambulatory blood pressure cuff 2 hours after receiving an oral dose. Doses will also be reduced if supine BP measured with the head of the bed elevated upon awakening in the morning exceeds 150/90 mmHg. Following a 1 week wash out period, subjects will receive the alternative treatment for 2 additional weeks and instrumented laboratory studies repeated.

Intervention Type DRUG

Placebo

Study #2 -Patients will randomized to receive Northera or placebo for two weeks after which they will return for instrumented tilt studies as in Study 1. Doses of Northera will be titrated upwards by 100mg/dose every 48 hours from a starting dose of 100mg three times a day to a maximum of 600mg three times a day. Doses will be reduced to the preceding dose if systolic BP\>140mmHg or diastolic BP\>80mmHg measured in the seated position at home using an automated ambulatory blood pressure cuff 2 hours after receiving an oral dose. Doses will also be reduced if supine BP measured with the head of the bed elevated upon awakening in the morning exceeds 150/90 mmHg. Following a 1 week wash out period, subjects will receive the alternative treatment for 2 additional weeks and instrumented laboratory studies repeated.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Both male and female participants are being studied
* Ages 18-30 years old
* POTS cases will be referred for day-to-day Orthostatic Intolerance (OI) with ≥3 symptoms for \>6 months.
* POTS will be confirmed by medical history indicating chronic OI, and by a prior 700 tilt table test or standing test showing excessive tachycardia and symptoms OI in the absence of hypotension.
* VVS (fainting) subjects will have at least 2 episodes of postural VVS during the past calendar year.
* Healthy volunteers will be included for Study #1

Exclusion Criteria

* Only those free from all systemic illnesses will be eligible to participate. This excludes patients with illnesses associated with autonomic dysfunction such as diabetes, renal disease, congestive heart failure, systemic hypertension, acute and chronic inflammatory diseases, neoplasm, immune mediated disease, trauma, obesity, cancer, supine or upright hypertension, and peripheral vascular disease.
* No subjects will be taking neurally active, or vasoactive drugs. Prior medication will be stopped for at least 2 weeks.

Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes