Peripheral Dopamine in Postural Tachycardia Syndrome
Condition: Postural Tachycardia Syndrome; Orthostatic Intolerance
MeSH terms: Postural Orthostatic Tachycardia Syndrome; Orthostatic Intolerance; Tachycardia; Syndrome
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of the proposed research is to determine how changes in kidney dopamine (DA)
      activity influence urinary sodium excretion. We will decrease DA activity in the kidney by
      inhibiting DA synthesis via carbidopa administration. We want to compare findings in normal
      volunteers and in patients with postural tachycardia syndrome (POTS). We will test the null
      hypothesis (Ho) that the effects of oral carbidopa administration on urinary sodium excretion
      will not differ between patients with POTS and healthy volunteers.
    

Detailed description: 
      We will determine whether inhibition of renal dopamine formation by carbidopa administration
      leads to a decrease in urinary excretion of dopamine and sodium and whether the response
      differs in POTS and control populations. Carbidopa effects will be compared to those of a
      matching placebo, and the sequence of treatments (carbidopa before placebo or placebo before
      carbidopa) will be randomized.

      Each subject will undergo a complete history and physical examination, including an
      electrocardiogram (EKG).

        -  After achieving sodium balance on a 200 mEq/day sodium diet, subjects will collect urine
           over 24hr for baseline assessment of sodium and catecholamines.

        -  On this day, the subjects will be admitted to the CRC.

        -  An 18 gauge intravenous catheter will be inserted in order to draw blood.

        -  The subjects will fast from 7 pm until after the next morning's testing.

        -  In the morning, while still supine after the overnight sleep, heart rate and blood
           pressure will be recorded, and blood will be drawn. The subjects will then stand for 10
           minutes. Heart rate and blood pressure will be measured at intervals, and an upright
           blood sample will be collected.

        -  The subjects will be asked to collect their urine to end the 24hr urine collection.
           Another 24hr urine collection will be started.

        -  Treatment A (Carbidopa 200mg or placebo) will be given orally following the void, at
           approximately 7 am. Additional doses will be taken every 6 hours with the last dose at 7
           am the following morning.

        -  Subjects will be free to follow their normal routine during the day until returning to
           the CRC for the night. However, they will need to consume the 200 mEq/day study diet for
           each meal, collect all urine, and take study medication on schedule

        -  After returning to the CRC, the subjects will fast after 7 pm.

        -  In the morning, supine and standing heart rate and blood pressure will be recorded, and
           the subjects will be asked to collect their urine to end the 24hr urine collection.

        -  The final dose of study medication (Carbidopa 200mg or placebo) will be given orally
           following the void, at approximately 7 am.

        -  Supine heart rate and blood pressure will be measured and supine blood samples will be
           collected hourly for 4 hours after the treatment and at 8 hours after the treatment.
           Subjects must rest supine for at least 30 minutes before each blood draw.

        -  At 2 hours after treatment, subjects will stand for 10 minutes for upright blood
           pressure and heart rate measurements and collection of an upright blood sample, as
           described above. Participants will be asked to rate the severity of common orthostatic
           symptoms while supine and upright.

        -  Urine will be collected for two 4-hour periods after treatment and from 8 hours to 24
           hours after treatment.

        -  Fixed-sodium study diet will be provided after the 4-hour measurements and in the
           evening.

      After at least a 1 day washout period, the study will be repeated with Treatment B
    

Intervention name(s): Carbidopa; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 200 mg every 6 hours for 5 doses given orally; every 6 hours for 5 doses, given orally, and matching Carbidopa
Intervention MeSH terms: Carbidopa
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Other
Keywords: Dopamine; Natriuresis; Catecholamines