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