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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01563107
Recruitment Status : Completed
First Posted : March 26, 2012
Results First Posted : January 25, 2022
Last Update Posted : January 25, 2022
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Alfredo Gamboa, Vanderbilt University Medical Center

Brief Summary:
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 or disease Intervention/treatment Phase
Postural Orthostatic Tachycardia Syndrome Radiation: Plasma Volume Procedure: Exercise Capacity Test - Bicycle Procedure: Posture Study Not Applicable

Detailed Description:

Study Day 1

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

Study Days 2-5

  • Continue 24hr 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 24hr Holter combined ECG monitor and BP monitor from subject
  • Continue 24hr 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
  • Nothing by mouth (NPO) after midnight for study next day

Study Day 7

  • Awaken early (~6am) to void (still collecting 24hr 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 increased 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)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomization tables will be used to determine whether the 10 milliequivalents (mEq) sodium/day or 300 mEq sodium/day diet will be consumed first. Both diets will be completed on each subject (randomized crossover study), so all of the study procedures (after screening) will be repeated.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Dietary Sodium's Effect on Urinary Sodium and Dopamine Excretion in Patients With Postural Tachycardia Syndrome
Study Start Date : March 2012
Actual Primary Completion Date : December 2020
Actual Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sodium

Arm Intervention/treatment
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. The high sodium diet will provide 300 milliequivalents (mEq) sodium/day.
Radiation: Plasma 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 breathe 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
POTS and healthy controls will be randomly assigned the order of dietary sodium levels. All procedures are performed at both levels. The low sodium diet will provide 10 mEq sodium/day.
Radiation: Plasma 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 breathe 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




Primary Outcome Measures :
  1. 24hr Urinary Sodium [ Time Frame: Day 6 am - Day 7 am for each dietary sodium level ]
    Amount of sodium excreted in urine over 24hr ending on Day 7

  2. 24hr Urinary Dopamine [ Time Frame: Between Day 6 am - Day 7 am of each dietary sodium level ]
    Amount of dopamine excreted in urine over 24 hours ending on Day 7


Secondary Outcome Measures :
  1. Plasma Volume [ Time Frame: after 7 days of each dietary sodium level ]
    Plasma volume (PV) was determined by the indicator tracer-dilution technique, using the DAXOR Blood Volume Analyzer (BVA)-100 system (DAXOR Corporation), on Day 7 of the low sodium and high sodium dietary interventions.

  2. Magnitude of Orthostatic Tachycardia [ Time Frame: Supine and upright heart rate were measured after 6 days of each dietary sodium level ]

    Whether the magnitude of the heart rate increase that occurs in patients with POTS when moving from a supine to an upright position is attenuated by a High Sodium diet relative to a Low Sodium diet.

    Heart rate was assessed after overnight rest and fasting after midnight, following at least 60 minutes of lying quietly. Heart rate was then measured at intervals after subjects had been standing for up to 30 minutes (as tolerated). Differences between supine and standing values are presented for 5 minutes standing (or maximal stand if <5 minutes) since several patients were unable to stand for 10 minutes.

    Data in POTS patients were compared to that of Healthy Controls.


  3. Upright Symptom Score [ Time Frame: Upright symptoms were assessed on the 6th day of low or high sodium diet. ]

    Whether upright symptoms were improved in patients with POTS on a High Sodium diet relative to a Low Sodium diet.

    Patients were asked to report their standing symptom burden at the end of the Stand portion of the posture study, using the Vanderbilt Orthostatic Symptoms Scale (VOSS). They rated the severity of nine symptoms (palpitations, lightheadedness, mental confusion, blurred vision, shortness of breath, tremulousness, chest discomfort, headache, and nausea) on a scale ranging from a minimum of 0 (reflecting an absence of symptoms) to a maximum score of 10. The sum of the individual symptom scores was used to calculate orthostatic symptom burden for each participant. The lowest possible total score was 0, if a participant scored all 9 questions as 0, and the highest possible score was 90, if a participant scored all 9 questions as 10. Higher scores indicated worse symptoms.


  4. Urinary Sodium Following Change in Dietary Sodium Days 1-2 [ Time Frame: 24 hour collections ending on Day 2 of each diet phase ]
    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.

  5. Urinary Dopamine Following Change in Dietary Sodium Days1-2 [ Time Frame: 24 hour collections ending on Day 2 of each dietary sodium phase ]
    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.

  6. Urinary Sodium Following Change in Dietary Sodium Days 2-3 [ Time Frame: 24 hour collections ending on Day 3 of each diet phase ]
    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.

  7. Urinary Sodium Following Change in Dietary Sodium Days 3-4 [ Time Frame: 24 hour collections ending on Day 4 of each diet phase ]
    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.

  8. Urinary Sodium Following Change in Dietary Sodium Days 4-5 [ Time Frame: 24 hour collections ending on Day 5 of each diet phase ]
    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

  9. Urinary Sodium Following Change in Dietary Sodium Days 5-6 [ Time Frame: 24 hour collections ending on Day 6 of each diet phase ]
    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.

  10. Urinary Dopamine Following Change in Dietary Sodium Days 2-3 [ Time Frame: 24 hour collections ending on Day 3 of each dietary sodium phase ]
    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.

  11. Urinary Dopamine Following Change in Dietary Sodium Days 3-4 [ Time Frame: 24 hour collections ending on Day 4 of each dietary sodium phase ]
    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.

  12. Urinary Dopamine Following Change in Dietary Sodium Days 4-5 [ Time Frame: 24 hour collections ending on Day 5 of each dietary sodium phase ]
    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.

  13. Urinary Dopamine Following Change in Dietary Sodium Days 5-6 [ Time Frame: 24 hour collections ending on Day 6 of each dietary sodium phase ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes 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
  • Patients who Increase heart rate ≥30 beats/min with position change from supine to standing (10 minutes)
  • For patients, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01563107


Locations
Layout table for location information
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Alfredo Gamboa, MD Vanderbilt University Medical Center
  Study Documents (Full-Text)

Documents provided by Alfredo Gamboa, Vanderbilt University Medical Center:
Layout table for additonal information
Responsible Party: Alfredo Gamboa, Associate Professor, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT01563107    
Other Study ID Numbers: VUMC 111633
R01HL071784 ( U.S. NIH Grant/Contract )
First Posted: March 26, 2012    Key Record Dates
Results First Posted: January 25, 2022
Last Update Posted: January 25, 2022
Last Verified: December 2021
Keywords provided by Alfredo Gamboa, Vanderbilt University Medical Center:
Orthostatic Intolerance
Tachycardia
Orthostatic Hypotension
Sodium
Additional relevant MeSH terms:
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Postural Orthostatic Tachycardia Syndrome
Tachycardia
Syndrome
Disease
Pathologic Processes
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Cardiac Conduction System Disease
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases