Peripheral Dopamine in Postural Tachycardia Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Emily M. Garland, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00685919
First received: May 27, 2008
Last updated: May 12, 2014
Last verified: May 2014
  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 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 2
Phase 3

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:


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 2015
Estimated Primary Completion Date: May 2015 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Publications:
Responsible Party: Emily M. Garland, Research Associate Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00685919     History of Changes
Other Study ID Numbers: 101499, HL071784-05A1
Study First Received: May 27, 2008
Last Updated: May 12, 2014
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:
Tachycardia
Postural Orthostatic Tachycardia Syndrome
Orthostatic Intolerance
Mitral Valve Prolapse
Neurocirculatory Asthenia
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 August 20, 2014