Dietary Salt in Postural Tachycardia Syndrome

NCT ID: NCT01547117

Last Updated: 2022-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2021-12-31

Brief 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 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)

Conditions

Postural Orthostatic Tachycardia Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

High Sodium Level

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.

Group Type: EXPERIMENTAL

Blood Volume

Intervention Type: RADIATION

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 Volume

Intervention Type: RADIATION

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 - Bicycle

Intervention Type: PROCEDURE

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 Study

Intervention Type: PROCEDURE

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.

Low Sodium Dietary Level

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.

Group Type: EXPERIMENTAL

Blood Volume

Intervention Type: RADIATION

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 Volume

Intervention Type: RADIATION

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 - Bicycle

Intervention Type: PROCEDURE

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 Study

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: RADIATION

Total Blood Volume

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.

Intervention Type: RADIATION

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

Other Intervention Names

carbon monoxide (CO)-red blood cell (RBC) Blood Volume; DAXOR; VO2 Max (maximal oxygen consumption); Standing Orthostatic Challenge

Eligibility Criteria

Inclusion Criteria

• 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
• 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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Alfredo Gamboa

Research Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alfredo J Gamboa, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37393658 (View on PubMed)

Garland 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.

Reference Type: DERIVED

PMID: 33926653 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01HL102387

Identifier Type: NIH

Identifier Source: secondary_id

View Link

111261

Identifier Type: -

Identifier Source: org_study_id