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

Northera Improves Postural Tachycardia Syndrome (POTS) and Postural

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.

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:

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.