High Salt Diet for POTS

(CASA-POTS Trial)

Overseen By Tanya Siddiqui, MBBS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Must not be taking: Fludrocortisone

Disqualifiers: Pregnancy, Anxiety, Anemia, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using fludrocortisone or have received IV saline in the last 2 months.

What data supports the effectiveness of the drug Sodium Chloride Capsules for POTS?

There is no direct evidence from the provided research articles that supports the effectiveness of Sodium Chloride Capsules specifically for POTS. However, sodium intake is known to affect blood pressure, and managing blood pressure is often a component of treating POTS. ^{1 2 3 4 5}

Is a high salt diet generally safe for humans?

Research suggests that while high salt intake can increase blood pressure, it does not necessarily jeopardize blood pressure control in patients already on antihypertensive medication. However, high salt intake is associated with a higher risk of cardiovascular disease, so it should be consumed in moderation. ^{1 6 7 8 9}

How does the drug Sodium Chloride Capsules differ from other treatments for POTS?

Sodium Chloride Capsules are unique for POTS as they involve increasing salt intake, which is contrary to typical advice for conditions like hypertension where reducing sodium is recommended. This approach aims to increase blood volume and improve symptoms, which is different from other treatments that might focus on heart rate or blood pressure control. ^{1 5 10 11 12}

What is the purpose of this trial?

Many patients with postural orthostatic tachycardia syndrome (POTS) have decreased plasma volume. Current POTS guidelines recommend \~10 g of salt and 2-3 L of fluid per day. Despite this recommendation, there is no long term data evaluating the use of salt in POTS. This randomized, placebo-controlled cross-over trial will evaluate a high salt diet, compared to a normal salt diet over a period of 3 months. Participants will complete 3 in lab evaluations including autonomic function testing, tilt table testing, blood volume and urine sodium evaluation, plasma catecholamine measurements and and cytokine measurements.

Research Team

Satish R Raj

Principal Investigator

University of Calgary

Eligibility Criteria

The trial is for Canadian residents aged 18-60 with POTS, who experience a rapid heartbeat upon standing but don't have a drop in blood pressure. Participants must be able to visit the Calgary Autonomic Research Clinic and should not have orthostatic hypotension.

Inclusion Criteria

Ability to attend the Calgary Autonomic Research Clinic in Calgary

Resident of Canada

I feel better lying down due to chronic dizziness or faintness.

Exclusion Criteria

Other factors which in the investigator's opinion would prevent the participant from completing the protocol, including poor compliance during previous studies

Pregnant (self-reported)

Participants with somatization or severe anxiety symptoms will be excluded

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment - Moderate Dietary Salt Plus Additional Salt

Participants receive a moderate dietary salt plus additional salt diet for 6 weeks, including autonomic function testing and blood volume assessment

6 weeks

1 visit (in-person) at the end of the arm

Treatment - Moderate Dietary Salt Alone (Placebo)

Participants receive a moderate dietary salt alone diet for 6 weeks, including autonomic function testing and blood volume assessment

6 weeks

1 visit (in-person) at the end of the arm

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sodium Chloride Capsules

Trial Overview This study tests if taking extra salt (sodium chloride capsules) helps manage POTS symptoms compared to placebo (microcrystalline cellulose capsules). It's a cross-over trial where participants switch between high salt and normal diets over three months, with lab evaluations.

Participant Groups

Group I: Moderate Dietary Salt Plus Additional Salt Experimental Treatment 1 Intervention

6 grams of salt in slow release capsules combined with 6 grams of salt in the diet.

Group II: Moderate Dietary Salt Alone Placebo Group 1 Intervention

6 grams of microcrystalline cellulose in slow release capsules combined with 6 grams of salt in the diet.

Sodium Chloride Capsules is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Sodium Chloride for:

• Postural Orthostatic Tachycardia Syndrome (POTS)

Approved in United States as Sodium Chloride for:

• Postural Orthostatic Tachycardia Syndrome (POTS)
• Vasovagal Syncope (VVS)

Approved in European Union as Sodium Chloride for:

• Postural Orthostatic Tachycardia Syndrome (POTS)
• Vasovagal Syncope (VVS)

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Findings from Research

High sodium intake (over 6 g/day) is linked to an increased risk of cardiovascular disease (CVD), while very low intake (under 3 g/day) is also associated with higher risk, suggesting that both extremes of sodium consumption can be harmful.

The optimal sodium intake for minimizing CVD risk appears to be between 3-5 g/day, based on recent prospective cohort studies, but further randomized controlled trials are needed to confirm this optimal range.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence relating sodium intake to blood pressure and CVD. O'Donnell, M., Mente, A., Yusuf, S.[2021]

Reducing daily sodium intake by 1840 mg could prevent approximately 11,550 cardiovascular disease events annually in Canada, highlighting the significant impact of dietary changes on heart health.

The study suggests that a sodium reduction from 1200 mg to 2400 mg per day could lead to a decrease in cardiovascular events ranging from 8300 to 16,800 per year, emphasizing the importance of sodium intake in managing cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing dietary sodium and decreases in cardiovascular disease in Canada. Penz, ED., Joffres, MR., Campbell, NR.[2021]

Potassium supplementation significantly reduces blood pressure in hypertensive patients with high salt intake, showing a pooled reduction of -9.5 mmHg for systolic and -6.4 mmHg for diastolic pressure based on a meta-analysis of 10 studies.

The effectiveness of potassium treatment is influenced by salt intake levels, with patients on lower salt diets experiencing minimal benefits, suggesting that previous analyses may have underestimated potassium's potential in managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium treatment for hypertension in patients with high salt intake: a meta-analysis. van Bommel, E., Cleophas, T.[2012]

In a study involving normal subjects, potassium supplementation with chloride increased urinary potassium and chloride excretion, indicating that these supplements affect electrolyte balance in the body.

The research found that chloride titrators remain reliable for estimating dietary sodium intake, even with varying levels of potassium chloride intake, allowing for predictable adjustments in interpretation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of chloride-containing potassium supplements on chloride titrator estimates of dietary sodium intake. Luft, FC., Sloan, RS., Fineberg, NS.[2019]

In a study of 23 patients with idiopathic hypertension, those who received potassium chloride (KCl) supplements showed a significantly lower increase in mean blood pressure when consuming a high sodium chloride (NaCl) diet compared to those who did not receive KCl (p < 0.001).

KCl supplementation led to less sodium retention, lower weight gain, and reduced increases in plasma volume and cardiac output during high NaCl intake, suggesting that KCl helps mitigate blood pressure rises by promoting natriuresis and reducing sympathetic nervous system activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic and endocrine changes associated with potassium supplementation in sodium-loaded hypertensives. Fujita, T., Ando, K.[2016]

In a study involving 11 patients with mild to moderate essential hypertension, adding sodium chloride to their normal diet did not significantly affect blood pressure control over a 6-week period.

The results suggest that excess dietary sodium does not compromise blood pressure management in patients already treated with various hypotensive agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased dietary sodium chloride in patients treated with antihypertensive drugs. Carney, SL., Gillies, AH., Smith, AJ., et al.[2019]

A recent study, the Salt Substitute and Stroke Study (SSaSS), found that using a low sodium salt substitute with potassium significantly reduced blood pressure, cardiovascular disease, and mortality among Chinese adults, suggesting benefits of dietary sodium restriction for those with high baseline intake.

While aiming for sodium intakes of 2-3g/day is recommended for the general population and as low as 2g/day for individuals with hypertension or cardiovascular disease, there are still questions about the feasibility and potential risks of maintaining such low sodium levels in everyday life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salt restriction for treatment of hypertension - current state and future directions. Nolan, P., McEvoy, JW.[2023]

High salt intake, primarily from sodium chloride, has been linked to various health risks, prompting growing concern in dietary guidelines.

The literature indicates a need for increased awareness and potential dietary adjustments to mitigate the health risks associated with excessive salt consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Intake and Related Diseases 2.0. Durazzo, A., Lombardi-Boccia, G., Santini, A., et al.[2022]

Replacing sodium chloride with potassium chloride in food products could significantly increase potassium intake, with a median increase of 453 mg/day for a 20% replacement and up to 733 mg/day for a complete replacement, based on a study of 2106 participants.

This reformulation strategy not only helps reduce sodium intake to meet health guidelines but also supports better compliance with potassium intake recommendations, while remaining safe for the general adult population according to EFSA guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Impact of Adding Potassium Chloride to Foods as a Sodium Reduction Technique. van Buren, L., Dötsch-Klerk, M., Seewi, G., et al.[2022]

In a study of 108 participants, reducing dietary sodium intake from 140 to 60 mmol/d while maintaining a high potassium diet led to a significant decrease in home systolic blood pressure by 2.5 mm Hg, indicating that lower sodium can effectively help manage blood pressure.

The study demonstrated that a low sodium diet (50 mmol/d) combined with high potassium intake (over 80 mmol/d) not only reduced urinary sodium levels but also increased urinary potassium, suggesting that this dietary approach could be beneficial for blood pressure control in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreasing dietary sodium while following a self-selected potassium-rich diet reduces blood pressure. Nowson, CA., Morgan, TO., Gibbons, C.[2018]

A low sodium diet (1 g Na daily) showed only a modest reduction in blood pressure (4 mm Hg systolic and 3 mm Hg diastolic) among 65 hypertensive patients, indicating limited efficacy for those already on medication.

Despite the modest benefits, many patients struggled with dietary compliance, as 28% still added salt to their cooking, and 55% had sodium excretion above 80 mmol, suggesting that adherence to low sodium advice is a significant challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is low salt dietary advice a useful therapy in hypertensive patients with poorly controlled blood pressure? Bulpitt, CJ., Daymond, M., Bulpitt, PF., et al.[2016]

In a study of 40 hypertensive patients, a moderate reduction in sodium intake combined with a potassium-rich salt alternative (Pansalt) led to a significant reduction in casual blood pressure (BP) by 13/8 mmHg compared to 8/5 mmHg in those using standard salt, although no significant changes were observed in 24-hour ambulatory BP.

Despite the BP reductions, the study found that neither sodium restriction nor potassium supplementation significantly affected total peripheral resistance or central hemodynamics over the 6-month period, suggesting that these dietary changes alone may not be sufficient for long-term management of essential hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unchanged central hemodynamics after six months of moderate sodium restriction with or without potassium supplement in essential hypertension. Omvik, P., Myking, OL.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evidence relating sodium intake to blood pressure and CVD. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Reducing dietary sodium and decreases in cardiovascular disease in Canada. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Potassium treatment for hypertension in patients with high salt intake: a meta-analysis. [2012]

4. United States pubmed.ncbi.nlm.nih.gov

The effect of chloride-containing potassium supplements on chloride titrator estimates of dietary sodium intake. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Hemodynamic and endocrine changes associated with potassium supplementation in sodium-loaded hypertensives. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Increased dietary sodium chloride in patients treated with antihypertensive drugs. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Salt restriction for treatment of hypertension - current state and future directions. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Sodium Intake and Related Diseases 2.0. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Dietary Impact of Adding Potassium Chloride to Foods as a Sodium Reduction Technique. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Decreasing dietary sodium while following a self-selected potassium-rich diet reduces blood pressure. [2018]

11. Finland pubmed.ncbi.nlm.nih.gov

Is low salt dietary advice a useful therapy in hypertensive patients with poorly controlled blood pressure? [2016]

12. England pubmed.ncbi.nlm.nih.gov

Unchanged central hemodynamics after six months of moderate sodium restriction with or without potassium supplement in essential hypertension. [2019]