Postural Orthostatic Tachycardia SyndromeNCT01547117
Dietary Salt in Postural Tachycardia Syndrome
A study testing Blood Volume, Total Blood Volume and Exercise Capacity Test - Bicycle in people with Postural Orthostatic Tachycardia Syndrome, run by Vanderbilt University at 1 site in United States.
Trial summary
Patients with POTS may not adequately expand their plasma volume in response to a high-sodium (Na+) diet. Mechanisms involved in the regulation of plasma volume, such as the renin-angiotensin-aldosterone system and renal dopamine, may be impaired in POTS and may respond inappropriately to changes in dietary sodium.The… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Postural Orthostatic Tachycardia Syndrome
- What is being tested?
- Blood Volume, Total Blood Volume and Exercise Capacity Test - Bicycle
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Dec 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- Age between 18-50 years old
- Non-smokers
- Premenopausal patients with POTS and healthy volunteers
Show all 9Show fewer
- 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
Who cannot join
- Smokers
- Overt cause for postural tachycardia, i.e., acute dehydration
- Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or screening results
- Pregnant (positive pregnancy test) or breastfeeding
- Hypertension defined as supine resting BP>145/95 mmHg off medications 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Patients with POTS may not adequately expand their plasma volume in response to a high-sodium (Na+) diet. Mechanisms involved in the regulation of plasma volume, such as the renin-angiotensin-aldosterone system and renal dopamine, may be impaired in POTS and may respond inappropriately to changes in dietary sodium.The purpose of this study is to determine (1) whether a high dietary sodium level appropriately expands plasma volume in POTS; (2) whether plasma renin activity and aldosterone are modified appropriately by changes in dietary sodium in POTS; and (3) whether patients with POTS have improvements in their orthostatic tachycardia and symptoms as a result of a high dietary sodium level.
Read the detailed description
Study Day 1
- Start 150 milliequivalents (mEq) Na+/day diet (POTS patients as inpatients; healthy control subjects with clinical research center (CRC)- provided outpatient diet)
- Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
- Blood work
- Blood volume - carbon monoxide rebreathing
Study Day 2
- Complete 24h urine
- 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; water ad lib
Study Day 3 - 5
- Continue STUDY DIET; water ad lib
- On Day 5, a 24 hr holter combined ECG monitor will be placed on the subjects.
Study Day 6
- Continue STUDY DIET; water ad lib
- Remove 24h Holter combined ECG monitor and BP monitor from subject
- Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
- Complete questionnaires
- Nothing by mouth (NPO) after midnight for study next day
Study Day 7 (BIG DAY)
- 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 3 tablespoons of blood in each body position to measure hormones that regulate blood pressure and blood volume
- Hormones to verify the subject's phase of menstrual cycle
- Serum/plasma aliquots for future analysis
- 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
- Autonomic Function Test with Cardiac Output and Brief Tilt
- The subject will be tilted up to 60-75 degrees head-up tilt for up to 10 minutes to measure the changes in heart rate and blood pressure and symptoms with upright challenge.
- Blood volume - carbon monoxide rebreathing
- 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 to the first phase, the second phase is the remaining level)
- Being tested
- Blood Volume, Total Blood Volume, Exercise Capacity Test - Bicycle, Posture Study
- Keywords
- POTS, Orthostatic Intolerance, Orthostatic Tachycardia
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome, Orthostatic Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood VolumeRadiation
Also called carbon monoxide (CO)-red blood cell (RBC) Blood Volume
we will measure the amount of hemoglobin and myoglobin in the body by a procedure called CO rebreathing. One teaspoon of blood is taken before and after a small amount of CO has been absorbed into the bloodstream.
Total Blood VolumeRadiation
Also called DAXOR
Using injection of iodinated I-131 tagged human serum albumin nominally 25 microcuries of radiation, blood samples are drawn before and 30 minutes after injection.
Exercise Capacity Test - BicycleProcedure or surgery
Also called VO2 Max (maximal oxygen consumption)
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.
Posture StudyProcedure or surgery
Also called Standing Orthostatic Challenge
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.
| Study group | Role | What they receive |
|---|---|---|
| High Sodium Level | Experimental | 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. Receives: Radiation: Blood Volume; Radiation: Total Blood Volume; Procedure: Exercise Capacity Test - Bicycle; Procedure: Posture Study |
| Low Sodium Dietary Level | Experimental | 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. Receives: Radiation: Blood Volume; Radiation: Total Blood Volume; Procedure: Exercise Capacity Test - Bicycle; Procedure: Posture Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Volume
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. Outcome data are the absolute values for PV on Day 7 for each diet.
Measured: after 7 days of each dietary sodium level
Secondary outcomes (1)
Magnitude of Suppression of Plasma Renin Activity (From Low Sodium to High Sodium Diets)
Whether upright plasma renin activity was modified appropriately by changes in dietary sodium in POTS \& healthy controls. Outcome data are the absolute values for upright plasma renin activity on Day 7 of each diet.
Measured: Upright blood samples were collected after up to 30 minutes of standing on the 7th day of each dietary sodium intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionDec 2020
- Study completionDec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postural Orthostatic Tachycardia SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomization tables will be used to determine whether the 10 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)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Alfredo Gamboa, Vanderbilt University
- Investigators
- Alfredo J Gamboa, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01547117
- Sponsor's protocol ID
- 111261
- Other IDs
- R01HL102387
- Status last verified
- Jan 2022
- First submitted
- 2 Mar 2012
- Last updated
- 22 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Laurin JKH, Oyewunmi OA, Garland EM, Gamboa A, Nwazue VC, Paranjape SY, Black BK, Okamoto LE, Shibao CA, Biaggioni I, Robertson D, Diedrich A, Dupont WD, Sheldon RS, Raj SR. Adrenal gland response to adrenocorticotropic hormone is intact in patients with postural orthostatic tachycardia syndrome. Auton Neurosci. 2023 Sep;248:103105. doi: 10.1016/j.autneu.2023.103105. Epub 2023 Jun 24.
PubMed 37393658Garland EM, Gamboa A, Nwazue VC, Celedonio JE, Paranjape SY, Black BK, Okamoto LE, Shibao CA, Biaggioni I, Robertson D, Diedrich A, Dupont WD, Raj SR. Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome. J Am Coll Cardiol. 2021 May 4;77(17):2174-2184. doi: 10.1016/j.jacc.2021.03.005.
PubMed 33926653
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Salt in Postural Tachycardia Syndrome
- ClinicalTrials.gov ID
- NCT01547117
- Acronym / sponsor ID
- 111261
- Keywords
- POTS, Orthostatic Intolerance, Orthostatic Tachycardia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2012
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2021 (actual)
- First posted
- 7 Mar 2012 (estimated)
- Results
- Posted 8 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with POTS may not adequately expand their plasma volume in response to a high-sodium (Na+) diet. Mechanisms involved in the regulation of plasma volume, such as the renin-angiotensin-aldosterone system and renal dopamine, may be impaired in POTS and may respond inappropriately to changes in dietary sodium.The purpose of this study is to determine (1) whether a high dietary sodium level appropriately expands plasma volume in POTS; (2) whether plasma renin activity and aldosterone are modified appropriately by changes in dietary sodium in POTS; and (3) whether patients with POTS have improvements in their orthostatic tachycardia and symptoms as a result of a high dietary sodium level.
Detailed description
Study Day 1
- Start 150 milliequivalents (mEq) Na+/day diet (POTS patients as inpatients; healthy control subjects with clinical research center (CRC)- provided outpatient diet)
- Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
- Blood work
- Blood volume - carbon monoxide rebreathing
Study Day 2
- Complete 24h urine
- 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; water ad lib
Study Day 3 - 5
- Continue STUDY DIET; water ad lib
- On Day 5, a 24 hr holter combined ECG monitor will be placed on the subjects.
Study Day 6
- Continue STUDY DIET; water ad lib
- Remove 24h Holter combined ECG monitor and BP monitor from subject
- Start a 24h urine collection (for Na+, K+, Cr, fractionated catecholamines)
- Complete questionnaires
- Nothing by mouth (NPO) after midnight for study next day
Study Day 7 (BIG DAY)
- 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 3 tablespoons of blood in each body position to measure hormones that regulate blood pressure and blood volume
- Hormones to verify the subject's phase of menstrual cycle
- Serum/plasma aliquots for future analysis
- 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
- Autonomic Function Test with Cardiac Output and Brief Tilt
- The subject will be tilted up to 60-75 degrees head-up tilt for up to 10 minutes to measure the changes in heart rate and blood pressure and symptoms with upright challenge.
- Blood volume - carbon monoxide rebreathing
- 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 to the first phase, the second phase is the remaining level)
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomization tables will be used to determine whether the 10 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.
| Arm | Type | Receives |
|---|---|---|
| High Sodium Level | Experimental | Radiation: Blood Volume, Radiation: Total Blood Volume, Procedure: Exercise Capacity Test - Bicycle, Procedure: Posture StudyPOTS 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. |
| Low Sodium Dietary Level | Experimental | Radiation: Blood Volume, Radiation: Total Blood Volume, Procedure: Exercise Capacity Test - Bicycle, Procedure: Posture StudyPOTS 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
- Age between 18-50 years old
- Non-smokers
Key exclusion criteria (7 listed)
- Smokers
- Overt cause for postural tachycardia, i.e., acute dehydration
- Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or screening results
- Pregnant (positive pregnancy test) or breastfeeding
- Hypertension defined as supine resting BP>145/95 mmHg off medications or needing antihypertensive medication
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood VolumeAlso: carbon monoxide (CO)-red blood cell (RBC) Blood Volumewe will measure the amount of hemoglobin and myoglobin in the body by a procedure called CO rebreathing. One teaspoon of blood is taken before and after a small amount of CO has been absorbed into the bloodstream. | Radiation | High Sodium Level, Low Sodium Dietary Level |
| Total Blood VolumeAlso: DAXORUsing injection of iodinated I-131 tagged human serum albumin nominally 25 microcuries of radiation, blood samples are drawn before and 30 minutes after injection. | Radiation | High Sodium Level, Low Sodium Dietary Level |
| Exercise Capacity Test - BicycleAlso: VO2 Max (maximal oxygen consumption)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. | Procedure or surgery | High Sodium Level, Low Sodium Dietary Level |
| Posture StudyAlso: Standing Orthostatic ChallengeBlood 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. | Procedure or surgery | High Sodium Level, Low Sodium Dietary Level |
Primary outcome
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. Outcome data are the absolute values for PV on Day 7 for each diet.
1 secondary outcome
Magnitude of Suppression of Plasma Renin Activity (From Low Sodium to High Sodium Diets)
Time frame: Upright blood samples were collected after up to 30 minutes of standing on the 7th day of each dietary sodium intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37393658Laurin JKH, Oyewunmi OA, Garland EM, Gamboa A, Nwazue VC, Paranjape SY, Black BK, Okamoto LE, Shibao CA, Biaggioni I, Robertson D, Diedrich A, Dupont WD, Sheldon RS, Raj SR. Adrenal gland response to adrenocorticotropic hormone is intact in patients with postural orthostatic tachycardia syndrome. Auton Neurosci. 2023 Sep;248:103105. doi: 10.1016/j.autneu.2023.103105. Epub 2023 Jun 24.
- Derived from this study: PubMed 33926653Garland EM, Gamboa A, Nwazue VC, Celedonio JE, Paranjape SY, Black BK, Okamoto LE, Shibao CA, Biaggioni I, Robertson D, Diedrich A, Dupont WD, Raj SR. Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome. J Am Coll Cardiol. 2021 May 4;77(17):2174-2184. doi: 10.1016/j.jacc.2021.03.005.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alfredo J Gamboa, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood Volume, Total Blood Volume and Exercise Capacity Test - Bicycle in people with Postural Orthostatic Tachycardia Syndrome, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Volume (time frame: after 7 days of each dietary sodium level). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01547117, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2022.