Dietary Sodium's Effect on Urinary Sodium and Dopamine Excretion in Patients With Postural Tachycardia Syndrome
Condition: Postural Orthostatic Tachycardia Syndrome
MeSH terms: Postural Orthostatic Tachycardia Syndrome; Tachycardia; Syndrome
Study type: Interventional

Summary: 
      Patients with Postural Tachycardia Syndrome (POTS) may not adequately expand their plasma
      volume in response to a high sodium diet. Mechanisms involved in the regulation of plasma
      volume, such as the renin-angiotensin-aldosterone system and renal dopamine (DA), may be
      impaired in POTS and may respond inappropriately to changes in dietary sodium. The
      investigators propose that the changes in urinary sodium and dopamine excretion caused by
      consuming low-sodium and high-sodium diets will be different between patients with POTS and
      healthy volunteers. The purpose of this study is to determine (1) whether changes in dietary
      sodium level appropriately influence sodium excretion in POTS; (2) whether changes in dietary
      sodium level appropriately influence DA excretion in POTS; (3) whether a high dietary sodium
      level appropriately expands plasma volume in POTS; and (4) whether patients with POTS have
      improvements in their orthostatic tachycardia and symptoms as a result of a high dietary
      sodium level.
    

Detailed description: 
      Study Day 1

        -  Start 150 mEq Na+/day diet (POTS patients as inpatients; healthy control subjects with
           Clinical Research Center(CRC)- provided outpatient diet); consume 1.5-2 liters of water
           per day

        -  Start a 24hour (24hr) urine collection (for sodium (Na+), potassium (K+), creatinine
           (Cr), fractionated catecholamines)

        -  Blood work

      Study Days 2-5

        -  Continue 24hr urine collection

        -  Start STUDY DIET (10 mEq Na+/day or 300 mEq Na+/day in a random order) after 3 meals of
           150 mEq Na+/day are complete; consume 1.5-2 liters of water per day

        -  On Day 5, a 24 hr Holter combined ECG monitor and BP monitor will be placed on the
           subjects.

      Study Day 6

        -  Continue STUDY DIET; consume 1.5-2 liters of water per day

        -  Remove 24hr Holter combined ECG monitor and BP monitor from subject

        -  Continue 24hr urine collection (for Na+, K+, Cr, fractionated catecholamines)

        -  Admit to CRC in afternoon (healthy control subjects only, as POTS patients will have
           already been admitted). Each subject will spend the night in the CRC and remain supine

        -  Nothing by mouth (NPO) after midnight for study next day

      Study Day 7

        -  Awaken early (~6am) to void (still collecting 24hr urine)

        -  Patient returns to bed, IV catheter inserted

        -  Posture Study (in morning; between 7-8am ideally)

        -  Blood pressure and heart rate will be measured while supine and then while standing for
           up to 30 minutes

        -  We will draw blood in each body position to measure electrolytes and hormones that
           regulate blood pressure and blood volume

        -  Subjects will rate symptoms during supine period and at end of stand using Vanderbilt
           Orthostatic Symptoms Score (VOSS)

        -  Total Blood Volume (DAXOR)- using injection of iodinated I-131 tagged human serum
           albumin nominally 25 micro-Ci of radiation blood samples drawn through IV catheter
           before injection and for ~30 minutes post-injection (total - 25 ml)

        -  This will be done after supine assessment, but before standing the subject up

        -  Exercise Capacity Test (in the afternoon) Will estimate maximal oxygen consumption (VO2
           max). This test will be conducted on a stationary bicycle. Effort will be gradually
           increased while expired air is measured during exhaustive physical work.

      All procedures are repeated at least a month later with the 2nd level of dietary salt.
      (Randomized to high or low salt in the first phase, the second phase is the remaining level)
    

Intervention name(s): Plasma Volume; Exercise Capacity Test - Bicycle; Posture Study
Intervention type(s): Radiation; Procedure; Procedure
Intervention description(s): Using injection of iodinated I-131 tagged human serum albumin nominally 25 micro-Ci of radiation, blood samples are drawn before and 30 minutes after injection.; subjects breathe room air through a mouthpiece and exhale the air into a tube that connects to a machine (metabolic cart) that analyzes carbon dioxide and oxygen content, which allows the investigator to calculate the amount of oxygen they are using under resting and exercise conditions.; Blood pressure and heart rate will be measured while supine and then while standing for up to 30 minutes. Blood will be drawn in each position to measure hormones that regulate blood pressure and blood volume.
Other intervention name(s): DAXOR; VO2 Max (maximal oxygen consumption); Standing Orthostatic Challenge
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomization tables will be used to determine whether the 10 milliequivalents (mEq) sodium/day or 300 mEq sodium/day diet will be consumed first. Both diets will be completed on each subject (randomized crossover study), so all of the study procedures (after screening) will be repeated.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Orthostatic Intolerance; Tachycardia; Orthostatic Hypotension; Sodium