Background and Rationale:
Postural Orthostatic Tachycardia Syndrome (POTS) is a form of autonomic cardiovascular
disease, primarily in women, that is often disabling. The investigators and others have found
that many patients with postural tachycardia have decreased plasma volume. Current POTS
guidelines recommend ~10 g of salt and 2-3 L of fluid per day. In a proof of concept dietary
salt study, the investigators recently showed 6 days of a high salt diet (300 mEq/d),
compared to a low salt diet, increases plasma volume, reduced standing plasma norepinephrine,
and reduced HR. The high salt diet reduced the median orthostatic tachycardia by 14 bpm.
Currently there is only evidence showing the benefits of supplemental salt-intake over one
week. It is unknown whether the increased blood volume from high dietary salt intake will
persist over several weeks, or if an "escape mechanism" will reduce blood volumes back to
baseline levels. This longer-term clinical trial of high dietary salt and water will address
this "escape mechanism" and ongoing dietary compliance in POTS.
Research Question & Objectives:
Primary Hypothesis: The primary hypothesis is that after 6 weeks of a moderate dietary salt
plus additional salt diet, the upright HR will be lower than after 6 weeks on a moderate
dietary salt alone diet.
Secondary hypotheses: The secondary hypotheses include:
Symptoms evaluated using the VOSS symptom score after 6 weeks of a moderate dietary salt
plus additional salt diet will be reduced compared to after 6 weeks of a moderate
dietary salt alone diet;
Upright stroke volume after 6 weeks of a moderate dietary salt plus additional salt diet
will be increased compared to after 6 weeks of a moderate dietary salt alone diet;
Blood volume after 6 weeks of a moderate dietary salt plus additional salt diet will be
increased compared to after 6 weeks of a moderate dietary salt alone diet;
Upright plasma catecholamines after 6 weeks of a moderate dietary salt plus additional
salt diet will be increased compared to after 6 weeks of a moderate dietary salt alone
diet;
Quality of life after 6 weeks of a moderate dietary salt plus additional salt diet will
be increased compared to after 6 weeks of a moderate dietary salt alone diet.
- Methods: Interventions: All participants will be instructed to each 5-6 g of salt per
day in their diet. In the moderate dietary salt plus additional salt arm, participants
will receive blinded capsules that contain 6g of salt per day (12x 500g slow- release
capsules). They will take 2g of salt 3 times per day. Participants in the placebo arm
will receive blinded capsules that contain 6g of microcrystalline cellulose. Protocol
compliance will be assessed with 24h urine sodium.
Randomization: This is a blinded cross-over study. The investigators will randomize patients
to start with either salt capsules or placebo. After the 6-week study arm, participants will
cross-over to the second study arm.
Study Visit Schedule: The study will consist of three in-house study sessions: a baseline
assessment, and an assessment at the end of each study arm: moderate dietary salt plus
additional salt and placebo. The baseline visit will serve as a screening visit. Each study
session will take place over 1 day in the Autonomic Lab at the University of Calgary. There
will also be four 24hr urine sodium collections, and multiple online REDCap surveys.
In-Lab Evaluation: The in-lab evaluation sessions while consist of autonomic function testing
including a 10-minute tilt test, blood volume assessment, and supine and standing bloodwork.
An IV will be started for the blood work.
Urine Sodium: Participants will complete a 24-hr urine sodium test around the time of each
in-lab evaluation, as well as before the 1 week study wash in.
Study Surveys: At each assessment point (baseline and end of each arm), the investigators
will send participants a secure REDCap survey link. At the end of the study, participants
will also receive a patient experience survey. Participants will receive a total of 4
surveys.