Peripheral Dopamine in Postural Tachycardia Syndrome - Full Text View

Sponsor:	Vanderbilt University
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00685919

Purpose

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 levodopa and carbidopa administration on urinary sodium excretion will not differ between patients with POTS and healthy volunteers.

Condition	Intervention	Phase
Postural Tachycardia Syndrome Orthostatic Intolerance	Drug: Carbidopa Drug: Placebo	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Single Blind (Subject)
Official Title:	Kidney Dopamine Effects on Urinary Sodium Excretion in Postural Tachycardia Syndrome

Resource links provided by NLM:

Genetics Home Reference related topics: Brugada syndrome short QT syndrome

MedlinePlus related topics: Mitral Valve Prolapse

Drug Information available for: Dopamine Dopamine hydrochloride Carbidopa

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

The primary outcome is the urinary sodium concentration normalized to creatinine. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Blood pressure [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
Plasma catecholamines [ Time Frame: 8 hours ] [ Designated as safety issue: No ]
Urinary catecholamines [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
Plasma renin activity [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
Plasma sodium [ Time Frame: 8 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	70
Study Start Date:	May 2008
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Carbidopa 200 mg every 6 hours orally	Drug: Carbidopa 200 mg every 6 hours for 5 doses given orally
Placebo Comparator: 2	Drug: Placebo every 6 hours for 5 doses, given orally, and matching Intervention 1

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

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Patients diagnosed with POTS by the Vanderbilt Autonomic Dysfunction Center based on the following stringent criteria: 1) history of daily orthostatic symptoms for at least 6 months; 2) increase in heart rate (HR) of at least 30 bpm with standing or a standing HR of at least 120 bpm; 3) absence of orthostatic hypotension (defined as a fall in blood pressure (BP)>20/10 mm Hg); and 4) absence of conditions, such as dehydration, substantial weight loss, or systemic illnesses, that could provoke orthostatic intolerance
Upright plasma NE at least 600 pg/mL in patients
Non-smoking
Free of medications with the potential to influence BP
Able and willing to provide informed consent -

Exclusion Criteria:

Overt cause for postural tachycardia (such as acute dehydration)
Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or screening results
Positive urine b-hcg pregnancy test
Evidence of cardiac structural disease (by clinical examination or prior echocardiogram)
Hypertension defined as a BP>145/95 (off medications) or need for antihypertensive medications
Evidence of significant conduction system delay (QRS duration >120 ms) on electrocardiogram
Inability to give, or withdraw, informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00685919

Contacts

Contact: Bonnie K Black, BSN, CNP		adc.research@vanderbilt.edu
Contact: Emily M Garland, PhD		adc.research@vanderbilt.edu

Locations

United States, Tennessee
Vanderbilt University	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Bonnie K Black, BSN CNP adc.research@vanderbilt.edu

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:

David Robertson, MD

Vanderbilt University

More Information

Additional Information:

Website of the Vanderbilt Autonomic Dysfunction Center This link exits the ClinicalTrials.gov site

Publications:

Carey RM. Theodore Cooper Lecture: Renal dopamine system: paracrine regulator of sodium homeostasis and blood pressure. Hypertension. 2001 Sep;38(3):297-302. Review.

Goldstein DS, Stull R, Eisenhofer G, Gill JR Jr. Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans. Clin Sci (Lond). 1989 May;76(5):517-22.

Jose PA, Eisner GM, Felder RA. Renal dopamine and sodium homeostasis. Curr Hypertens Rep. 2000 Apr;2(2):174-83. Review.

Kuchel O, Buu NT, Unger T. Dopamine-sodium relationship: is dopamine a part of the endogenous natriuretic system? Contrib Nephrol. 1978;13:27-36.

Stokes GS, Monaghan JC, Pillai DN. Effects of carbidopa and of intravenous saline infusion into normal and hypertensive subjects on urinary free and conjugated dopamine. J Hypertens. 1997 Jul;15(7):761-8.

Jacob G, Robertson D, Mosqueda-Garcia R, Ertl AC, Robertson RM, Biaggioni I. Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system. Am J Med. 1997 Aug;103(2):128-33.

Responsible Party:	David Robertson, MD, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00685919 History of Changes
Other Study ID Numbers:	101499, HL071784-05A1
Study First Received:	May 27, 2008
Last Updated:	June 28, 2011
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration

Keywords provided by Vanderbilt University:

Dopamine
Natriuresis
Catecholamines

Additional relevant MeSH terms:

Orthostatic Intolerance
Mitral Valve Prolapse
Neurocirculatory Asthenia
Tachycardia
Postural Orthostatic Tachycardia Syndrome
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Heart Valve Prolapse
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Anxiety Disorders

Mental Disorders
Arrhythmias, Cardiac
Pathologic Processes
Carbidopa
Dopamine
Dopamine Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012