Dietary Sodium's Effect on Urinary Sodium and Dopamine Excretion in Patients With Postural Tachycardia Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Vanderbilt University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Emily M. Garland, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01563107
First received: March 22, 2012
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Postural Orthostatic Tachycardia Syndrome
Radiation: Total Blood Volume
Procedure: Exercise Capacity Test - Bicycle
Procedure: Posture Study

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Dietary Sodium's Effect on Urinary Sodium and Dopamine Excretion in Patients With Postural Tachycardia Syndrome

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Urinary sodium [ Time Frame: after 6 days of each dietary sodium level ] [ Designated as safety issue: No ]
    Amount of sodium excreted in urine over 24hr will be measured.

  • Urinary dopamine [ Time Frame: after 6 days of each dietary sodium level ] [ Designated as safety issue: No ]
    Amount of dopamine excreted in urine over 24 hours will be measured.


Secondary Outcome Measures:
  • Blood Volume [ Time Frame: after 6 days of each dietary sodium level ] [ Designated as safety issue: No ]
    DAXOR (131-I labelled albumin) blood volume assay

  • Change in Heart Rate with Standing [ Time Frame: After 6 days of each dietary sodium level ] [ Designated as safety issue: No ]
    Heart rate is measured while supine and standing during a Posture Study and the change in heart rate with standing is calculated.

  • Orthostatic Symptoms [ Time Frame: After 6 days of each dietary sodium level ] [ Designated as safety issue: No ]
    Symptoms will be assessed in the supine and upright postures to determine the Vanderbilt Orthostatic Symptoms Score.

  • Change in Urinary Sodium following Change in Dietary Sodium [ Time Frame: Days 1-5 of each dietary sodium level ] [ Designated as safety issue: No ]
    Urinary sodium excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.

  • Change in Urinary Dopamine following Change in Dietary Sodium [ Time Frame: Days 1-5 of each dietary sodium level ] [ Designated as safety issue: No ]
    Urinary dopamine excretion will be measured every 24 hours as the participant adapts from the 150 mEq Na/day diet to the 10 and 300 mEq Na/day diets.


Estimated Enrollment: 40
Study Start Date: March 2012
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Salt Diet
POTS and healthy controls will be randomly assigned the order of dietary sodium levels. All procedures are performed at both levels.
Radiation: Total Blood Volume
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.
Other Name: DAXOR
Procedure: Exercise Capacity Test - Bicycle
subjects breath 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.
Other Name: VO2 Max (maximal oxygen consumption)
Procedure: Posture Study
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 Name: Standing Orthostatic Challenge
Experimental: Low Salt Diet Radiation: Total Blood Volume
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.
Other Name: DAXOR
Procedure: Exercise Capacity Test - Bicycle
subjects breath 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.
Other Name: VO2 Max (maximal oxygen consumption)
Procedure: Posture Study
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 Name: Standing Orthostatic Challenge

Detailed Description:

Study Day 1

  • Start 150 mEq Na+/day diet (POTS patients as inpatients; healthy control subjects with CRC provided outpatient diet); consume 1.5-2 liters of water per day
  • Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
  • Blood work

Study Days 2-5

  • Continue 24h 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 24h Holter combined ECG monitor and BP monitor from subject
  • Continue 24h 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
  • NPO after midnight for study next day

Study Day 7

  • Awaken early (~6am) to void (still collecting 24h 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 increase 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)

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Premenopausal patients with POTS and healthy volunteers, 18-50 years old, who are non-smokers and free of medications with the potential to influence blood pressure
  • Patients diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic Dysfunction Center
  • Increase in heart rate ≥30 beats/min with position change from supine to standing (10 minutes)
  • Chronic symptoms consistent with POTS that are worse when upright and get better with recumbence
  • Only female participants are eligible. Since 80-90% of POTS patients are female, and there can be differences in measures with the menstrual cycle, including a small number of males might introduce a significant amount of noise.
  • Able and willing to provide informed consent

Exclusion Criteria:

  • Smokers
  • Overt cause for postural tachycardia, i.e., acute dehydration
  • Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or screening results
  • Positive pregnancy test or breastfeeding
  • Hypertension defined as BP>145/95 off medications when supine or needing antihypertensive medication
  • Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies or an unpredictable schedule
  • Unable to give 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: NCT01563107

Locations
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Victor Nwazue, MD    615-322-2931    adcresearch@vanderbilt.edu   
Contact: Emily M Garland, PhD, MSCI    615-322-2931    adcresearch@vanderbilt.edu   
Principal Investigator: Emily M Garland, PhD         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Emily M Garland, PhD, MSCI Vanderbilt University
  More Information

Additional Information:
No publications provided

Responsible Party: Emily M. Garland, Research Associate Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01563107     History of Changes
Other Study ID Numbers: VUMC 111633, R01HL071784
Study First Received: March 22, 2012
Last Updated: May 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Orthostatic Intolerance
Tachycardia
Orthostatic Hypotension
Sodium

Additional relevant MeSH terms:
Orthostatic Intolerance
Syndrome
Tachycardia
Postural Orthostatic Tachycardia Syndrome
Disease
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on September 18, 2014