Peripheral Dopamine in Postural Tachycardia Syndrome
|Postural Tachycardia Syndrome Orthostatic Intolerance||Drug: Carbidopa Drug: Placebo||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Other
|Official Title:||Kidney Dopamine Effects on Urinary Sodium Excretion in Postural Tachycardia Syndrome|
- The primary outcome is the urinary sodium concentration normalized to creatinine. [ Time Frame: 24 hours ]
- Blood pressure [ Time Frame: 8 hours ]
- Plasma catecholamines [ Time Frame: 8 hours ]
- Urinary catecholamines [ Time Frame: 24 hours ]
- Plasma renin activity [ Time Frame: 2 hours ]
- Plasma sodium [ Time Frame: 8 hours ]
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||October 2018|
|Estimated Primary Completion Date:||October 2018 (Final data collection date for primary outcome measure)|
Carbidopa 200 mg every 6 hours orally
200 mg every 6 hours for 5 doses given orally
|Placebo Comparator: 2||
every 6 hours for 5 doses, given orally, and matching Intervention 1
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00685919
|United States, Tennessee|
|Vanderbilt University Medical Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||David Robertson, MD||Vanderbilt University|