Autoimmune Basis for Postural Tachycardia Syndrome

Postural tachycardia syndrome (POTS) is a debilitating disorder resulting from cardiovascular
autonomic dysfunction, has many causes and is very difficult to treat effectively. The
investigators have identified the presence of autoantibodies (immune proteins) directed
against some receptors of the autonomic nervous system that can cause patient's symptoms on
standing.

The present study is designed to test the hypothesis that patients with POTS harbor
functional autoantibodies to adrenergic receptors that lead to an excessive tachycardia
characteristic of POTS. For this purpose, this study will define the prevalence, burden, and
the in vivo physiological significance of these adrenergic antibodies in a well-phenotyped
and representative cohort of patients with POTS and a matched cohort of healthy control
subjects, and will characterize the stability of these autoantibodies over time in affected
POTS patients.

Inclusion Criteria:

- 18-50 years old

- Postural Tachycardia Syndrome: Heart rate increase >30 bpm from supine within 10 min
of standing, in the absence of orthostatic hypotension (>20/10 mmHg fall in blood
pressure), with chronic symptoms (> 6 months), and in the absence of other acute cause
of orthostatic tachycardia.

- Able and willing to provide informed consent

- Female premenopausal subjects must utilize adequate birth control and willingness to
undergo serum beta-hCG testing

- The subject must understand and be able to comply with the study procedures and
restrictions.

Exclusion Criteria:

- Hypertension (>150 mmHg systolic and >100 mmHg diastolic) based on history or findings
at screening.

- Orthostatic hypotension (consistent drop in blood pressure >20/10 mmHg with 10 min
stand)

- Pregnancy

- Cardiovascular disease, such as myocardial infarction within 6 months, angina
pectoris, significant arrhythmia (sinus tachycardia is not excluded), deep vein
thrombosis, pulmonary embolism

- History of serious neurologic disease

- History or presence of significant immunological or hematological disorders

- Clinically significant gastrointestinal impairment that could interfere with dietary
compliance or drug absorption

- Impaired hepatic function (aspartate amino transaminase and/or alanine amino
transaminase >1.5 x upper limit of normal range)

- Impaired renal function (serum creatinine >1.5 mg/dL)

- Hematocrit <28%

- Current or concurrent disease that could affect the absorption, action or disposition
of the drug, or clinical or laboratory assessments.

- Any underlying or acute disease requiring regular medication that could possibly pose
a threat to the subject or make implementation of the protocol or interpretation of
the study results difficult

- Inability to comply with the protocol

Healthy control subjects will be healthy, non-smoking and on no chronic medications at the
time of the study. Healthy control subjects will be group-matched to the POTS patients for
age and gender. We will attempt to study female patients in the first half of their
menstrual cycle to minimize cyclical variability.