Sodium Intake Modification for High Blood Pressure

Overseen By Joseph M Stock, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Delaware

Must not be taking: Psychiatric, hypertension

Disqualifiers: Cardiovascular, cancer, metabolic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the brain senses changes in blood salt levels, potentially enhancing understanding of blood pressure control. Participants will follow a diet with varying salt levels and receive a hypertonic saline solution (salty water) infusion to observe the brain's response. This research could lead to new methods for managing high blood pressure, a common health issue. Individuals with normal blood pressure, who do not smoke, have no major health issues, and are between the ages of 18 and 45 may be suitable for this study. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research that could improve blood pressure management.

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking psychiatric, neurological, anxiety, depression, and hypertension medications to participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that changing one's diet can safely and effectively manage blood pressure. For instance, reducing salt intake can lower the systolic blood pressure by about 6 to 11 points, easing stress on the heart and blood vessels. Many individuals with high blood pressure find these dietary changes beneficial and experience few side effects.

In contrast, hypertonic saline, a salt solution administered intravenously, carries some risks. Studies indicate it can cause side effects like dizziness, a fast heartbeat, and irritation. Some individuals might encounter more serious issues, such as increased blood pressure or swelling. However, when administered carefully, the risk of serious problems remains low.

Overall, dietary changes are generally easy to manage, while hypertonic saline requires careful monitoring to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores innovative ways to manage high blood pressure through dietary changes and advanced imaging techniques. Most treatments for high blood pressure rely on medications like ACE inhibitors or diuretics, but this trial examines the impact of modifying sodium intake directly. The study's first arm tests how the body responds to different salt levels, potentially leading to personalized dietary approaches. The second arm uses hypertonic saline infusions and advanced imaging to better understand how the brain senses sodium, offering fresh insights into hypertension's underlying mechanisms. These methods could pave the way for more tailored and effective hypertension treatments in the future.

What evidence suggests that this trial's treatments could be effective for high blood pressure?

Research has shown that dietary changes can significantly lower blood pressure. For instance, following a specific diet can reduce the risk of high blood pressure by 20%. One study found that certain diets can lower systolic blood pressure by about 3 points on average. In this trial, participants will undergo a Salt Sensitivity Assessment, which includes a 1-week high salt diet and a 1-week low salt diet, to evaluate the impact of dietary changes on blood pressure.

In contrast, hypertonic saline, a saltwater solution, raises blood pressure when administered through an IV. It is used in some medical situations to address conditions like high pressure inside the skull. This trial will also include a Functional Magnetic Resonance Imaging arm, where participants will receive hypertonic saline infusion to examine sodium sensing mechanisms. Although hypertonic saline increases blood pressure, its long-term effects on blood pressure remain under investigation. ^{6 7 8 9 10}

Who Is on the Research Team?

William B Farquhar, PhD

Principal Investigator

University of Delaware

Are You a Good Fit for This Trial?

This trial is for adults aged 18-45 with normal blood pressure and potassium levels, who have a BMI within the range of 18.5 to 30 kg/m2. It's designed for those without any known allergies or salt sensitivity issues that affect their blood pressure.

Inclusion Criteria

BMI: 18.5 kg/m2 - 30 kg/m2

Blood pressure: >100/60 mmHg and <130/80 mmHg

Serum potassium: 3.5 mmol/L - 5.5 mmol/L

Exclusion Criteria

I am taking medication for a psychiatric condition.

Abnormal ECG

Serum potassium: < 3.5 mmol/L or > 5.5 mmol/L

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Salt Sensitivity Assessment

Participants undergo a 1 week high salt diet and 1 week low salt diet to assess salt sensitivity

2 weeks

Functional Magnetic Resonance Imaging

Participants receive hypertonic saline infusion with and without NKCC2 antagonism to examine sodium sensing mechanisms

1 hour

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dietary Intervention
• Hypertonic Saline

Trial Overview

The study aims to understand how the brain detects changes in blood sodium levels and its role in controlling blood pressure. Participants will undergo dietary interventions and receive hypertonic saline to identify key brain regions involved in sodium sensing.

How Is the Trial Designed?

Group I: Hypernatremia without Furosemide first, then Hypernatremia + Furosemide Experimental Treatment 2 Interventions

Participants in this arm will undergo blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) on two separate days. On the first testing day, participants will receive a hypertonic saline infusion without NKCC2 antagonism (furosemide). On the second testing day, participants will receive a hypertonic saline infusion with NKCC2 antagonism (furosemide). This will enable us to examine sodium sensing mechanisms. The two conditions will be separated by at least 1 week washout. The hypertonic saline will be a 3% NaCl solution infused intravenously at a rate of 0.15 ml/kg/min for 30 minutes; the furosemide will be infused intravenously as a 40 mg bolus in 4mL of isotonic saline (0.9% NaCl) immediately prior to the hypertonic saline infusion.

Group II: Hypernatremia + Furosemide first, then Hypernatremia without Furosemide Experimental Treatment 2 Interventions

Participants in this arm will undergo blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) on two separate days. On the first testing day, participants will receive a hypertonic saline infusion with NKCC2 antagonism (furosemide). On the second testing day, participants will receive a hypertonic saline infusion without NKCC2 antagonism (furosemide). This will enable us to examine sodium sensing mechanisms. The two conditions will be separated by at least 1 week washout. The hypertonic saline will be a 3% NaCl solution infused intravenously at a rate of 0.15 ml/kg/min for 30 minutes; the furosemide will be infused intravenously as a 40 mg bolus in 4mL of isotonic saline (0.9% NaCl) immediately prior to the hypertonic saline infusion.

Who Is Running the Clinical Trial?

University of Delaware

Lead Sponsor

Trials

167

Recruited

25,700+

Published Research Related to This Trial

Restricting dietary sodium is a simple, safe, and effective nonpharmacologic approach to treating mild hypertension, making it a valuable option for patients, especially those on thiazide diuretics.

Overnight urinary collections can be used to estimate sodium intake, and using chemical chloride strips can help improve patient compliance with dietary restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium restriction in the treatment of hypertension. Luft, FC.[2004]

The Satter House Trial of Reduced Sodium Meals (SOTRUE) showed that a low sodium meal plan for 14 days in older adults led to a reduction in seated systolic blood pressure (SBP) from 123 to 112 mmHg, indicating potential benefits for blood pressure management.

While the low sodium diet did lower SBP by 4.8 mmHg compared to a typical sodium diet, the results were not statistically significant, suggesting that further research with a larger sample size and longer duration is necessary to confirm the efficacy and safety of low sodium meals in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of a Low Sodium Meal Plan on Blood Pressure in Older Adults: The SOTRUE Randomized Feasibility Trial. Juraschek, SP., Millar, CL., Foley, A., et al.[2021]

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]

High sodium intake is directly linked to increased blood pressure and hypertension, with significant public health benefits from reducing sodium consumption, as even a small decrease can lead to a notable drop in blood pressure over time.

A reduction of 1.3 grams of sodium per day could prevent a rise of about 5 mm Hg in systolic blood pressure from ages 25 to 55, potentially saving 150,000 lives each year, highlighting the need for industry regulation and consumer education to lower sodium levels in diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing the population burden of cardiovascular disease by reducing sodium intake: a report of the Council on Science and Public Health. Dickinson, BD., Havas, S.[2008]

Extreme changes in sodium intake can affect blood pressure in both people with normal blood pressure and those with high blood pressure, but the evidence is not strong enough to recommend a general reduction in sodium intake for everyone to prevent hypertension.

Studies show mixed results on the effectiveness of sodium restriction for managing hypertension, and many patients are unlikely to stick to a low-sodium diet without significant support, suggesting that low-sodium diets should not be the primary public health recommendation for treating high blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium manipulation in the management of hypertension. The view against its general use. Logan, AG.[2019]

A study involving 95 hypertensive participants showed that a low sodium diet (less than 60 mmol/day) significantly reduced blood pressure, with an average decrease of 6 mmHg in both supine and standing positions.

The study confirmed that dietary changes, including sodium restriction and adjustments in fat and fiber intake, were effectively implemented, indicating that sodium reduction plays a crucial role in managing hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A factorial study of fat and fibre changes and sodium restriction on blood pressure of human hypertensive subjects. Sciarrone, SE., Rouse, IL., Rogers, P., et al.[2019]

In a one-year study involving 48 hypertensive outpatients, a small-group management program that included feedback on dietary sodium levels was the most effective method for reducing sodium intake.

This group management approach outperformed both simple advice and intensive education in helping patients lower their dietary sodium, which could potentially reduce their reliance on antihypertensive medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salt restriction in hypertensive patients. Comparison of advice, education, and group management. Nugent, CA., Carnahan, JE., Sheehan, ET., et al.[2013]

A study involving 12 stable hypertensive patients found that while they believed they had significantly reduced their daily sodium intake after a single dietary counseling session, objective measurements showed no actual decrease in sodium consumption.

The results suggest that one-time dietary counseling may not be effective in achieving meaningful reductions in salt intake among hypertensive patients, indicating the need for more sustained interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of single-session dietary counseling to reduce salt intake in hypertensive patients. Buccicone, J., McAllister, RG.[2019]

A dietary sodium intake of 2.5 to 3 grams is recommended to meet nutritional needs and reduce the risk of hospitalizations, highlighting its efficacy in managing health outcomes.

Involving both patients and their family members in the process of adopting a low sodium diet, along with using motivational interviewing techniques, significantly enhances the likelihood of successful dietary changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What should we tell patients with heart failure about sodium restriction and how should we counsel them? Lennie, TA., Chung, ML., Moser, DK.[2022]

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