Dietary Sodium's Effect on Urinary Sodium and Dopamine Excretion in Patients With Postural Tachycardia Syndrome
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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 |
- 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.
- 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 |
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| 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 | |
| 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: | March 1, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Vanderbilt University:
|
Orthostatic Intolerance Tachycardia Orthostatic Hypotension Sodium |
Additional relevant MeSH terms:
|
Tachycardia Postural Orthostatic Tachycardia Syndrome Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Orthostatic Intolerance Primary Dysautonomias Autonomic Nervous System Diseases Nervous System Diseases Dopamine Cardiotonic Agents |
Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Protective Agents |
ClinicalTrials.gov processed this record on May 16, 2013