Salt Sensitivity of Blood PressureNCT05480722

Central Sodium Sensing: Implications for Blood Pressure Regulation

A study testing Hypertonic Saline with furosemide and Hypertonic Saline without furosemide in people with Salt Sensitivity of Blood Pressure, run by University of Delaware at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Salt Sensitivity of Blood Pressure
What is being tested?: Hypertonic Saline with furosemide and Hypertonic Saline without furosemide
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 1 siteUnited States
Study dates: 1 Jun 2022to 31 Jan 2025
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 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Age: 18 - 45 years
Blood pressure: >100/60 mmHg and <130/80 mmHg
BMI: 18.5 kg/m2 - 30 kg/m2
Serum potassium: 3.5 mmol/L - 5.5 mmol/L

Who cannot join

Age: < 18 years or > 45 years
Blood pressure: < 100/60 mmHg or > 130/80 mmHg
BMI: < 18.5 kg/m2 or > 30 kg/m2
Serum potassium: < 3.5 mmol/L or > 5.5 mmol/L
Abnormal ECG
History of - cardiovascular, cancer, metabolic, respiratory, renal disease

Show all 15Show fewer

Hormone replacement therapy
Current tobacco or nicotine use
Pregnant or nursing mothers
Major brain injury (concussions do not count)
Clinically diagnosed psychiatric or neurological disorder
Clinically diagnosed anxiety or depression
Psychiatric, neurological, anxiety or depression medications
Hypertension medications
Sulfonamide drug allergy

Trial locations and contacts

1 site in 1 country.

United States1 site

William B Farquhar
Newark, Delaware, 19713

Other trials in United States

About this study

The ability of the brain to sense changing sodium levels in the blood is critical in mediating the neurohumoral responses to hypernatremia, however, the mechanisms underlying sodium sensing in humans is poorly understood. The purpose of this study is to identify key sodium-sensing regions of the human brain in older adults and determine if the Na-K-2Cl co-transporter mediates the neurohumoral response to acute hypernatremia. Completion of this project will increase our understanding of blood pressure regulation, which has major public health implications.

Read the detailed description

The prevalence of hypertension is very high in older adults, and a major factor in hypertension is salt sensitivity of blood pressure (BP) and elevated sympathetic nerve activity (SNA). However, we know very little about how the human brain 'senses' sodium, and what molecular mechanisms are involved. Rodent studies have identified specialized sodium chloride (NaCl)-sensing neurons in the circumventricular organs (CVOs), which mediate NaCl-induced changes in SNA, arginine vasopressin (AVP), and BP. Recent data suggest the Na-K-2Cl co-transporter (NKCC2) is not kidney specific but is also expressed in brain regions that regulate whole body NaCl and water homeostasis. In addition, NKCC2 is accessible by drugs in the circulation since the CVOs lack a complete blood brain barrier. The objective of this R21 is to identify key NaCl-sensing regions of the brain in older adults and determine if NKCC2 mediates the neurohumoral response to acute hypernatremia. We seek to translate the prior rodent findings to humans by assessing neuronal activation (using blood oxygen level dependent functional magnetic resonance imaging, BOLD fMRI) as well as thirst, AVP, SNA and BP during an acute hypernatremic stimulus, with and without an NKCC2 antagonist (furosemide). This will enable us to assess the role of NKCC2 in NaCl sensing. The overall hypothesis is that acute hypernatremia will elicit detectable changes in the BOLD fMRI signal and increase thirst, AVP, SNA, and BP largely through NKCC2 in healthy older adults. Accordingly, the first specific aim is to identify the areas of the human brain that respond to acute hypernatremia and determine the role of NKCC2 in central NaCl- sensing. Acute hypernatremia will be induced with a 30-minute infusion of 3% NaCl delivered intravenously. Brain activity during the hypertonic saline infusion will be measured in regions such as the organum vasculosum laminae terminalis, subfornical organ, anterior cingulate cortex, hypothalamus, and insular cortex. The second specific aim is to determine the effect of acute hypernatremia on thirst, AVP, SNA, and BP, and determine the role of NKCC2 in mediating these responses. Salt sensitivity of BP will be individually assessed and comparisons will be made between those with a salt resistant and salt sensitive phenotype; we anticipate that acute hypernatremia will elicit changes in the BOLD fMRI signal and SNA \& AVP in all subjects, but the responses will be greater in those who are classified as salt sensitive. This would represent the first trial in healthy human subjects to identify a putative brain NaCl-sensing co-transporter, and we think the scope and innovative approaches are ideal for the R21 funding mechanism. Older adults are prone to hypertension, so it is critically important to understand how normotensive older adults centrally sense sodium, to provide a needed foundation for exploring the mechanistic underpinning of salt sensitive hypertension.

Conditions: Salt Sensitivity of Blood Pressure
Being tested: Hypertonic Saline with furosemide, Hypertonic Saline without furosemide

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Hypertonic Saline with furosemideOther
Subjects will undergo MRI with a hypertonic saline infusion with NKCC2 antagonism (furosemide). 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.
Hypertonic Saline without furosemideOther
Subjects will undergo MRI with a hypertonic saline infusion. The hypertonic saline will be a 3% NaCl solution infused intravenously at a rate of 0.15 ml/kg/min for 30 minutes.

Study groups in NCT05480722
Study group	Role	What they receive
Hypernatremia + Furosemide first, then Hypernatremia without Furosemide	Experimental	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. Receives: Other: Hypertonic Saline with furosemide; Other: Hypertonic Saline without furosemide
Hypernatremia without Furosemide first, then Hypernatremia + Furosemide	Experimental	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. Receives: Other: Hypertonic Saline with furosemide; Other: Hypertonic Saline without furosemide

What is being measured

The primary outcome is the main question the study is designed to answer.

Functional Connectivity Between the Subfornical Organ and Organum Vasculosum of the Lamina Terminalis (Z-score)
Functional connectivity between sodium sensing circumventricular organs (subfornical organ (SFO) and organum vasculosum of the lamina terminalis(OVLT)) was calculated (expressed as the z-score). Functional connectivity is a measure of the the correlation (or synchronization) of the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal time course between two brain regions. Pearson correlations were computed between the BOLD fMRI signal in the SFO and OVLT in a seed-to-seed functional connectivity analysis. Pearson correlations were converted to Z-scores using a Fisher's transform. A Z-score of 0 indicates no correlation between the BOLD fMRI signal between these 2 brain regions; a higher score indicates a greater, positive correlation between the BOLD fMRI signal in these 2 brain regions; a lower score indicates a greater, negative correlation between the fMRI signal in these 2 brain regions. This data does not have any clinical thresholds.
Measured: Functional connectivity (FC) was calculated at baseline (~10 min). Then, participants received a 30-minute hypertonic saline infusion (HSI) with or without furosemide before. FC was calculated during the early (0-15 min) and late phase (15-30 min) of HSI.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 202231 Jan 2025

First posted29 Jul 2022
Study start1 Jun 2022
Primary completion31 Jan 2025
Study completion31 Jan 2025

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.
Other trials for Salt Sensitivity of Blood PressureStudies 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: Non-randomised
Intervention model: Crossover
Model description: single blinded crossover design
Masking: Single blind
Who is masked: Participant
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05480722
Sponsor's protocol ID: 1808532
Status last verified: Nov 2025
First submitted: 27 Jul 2022
Last updated: 8 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Data will be shared upon reasonable request.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Beta-2 Adrenergic Receptor Polymorphic Variants: An Endotype of Salt Sensitive Hypertension (Beta2AR).
Genetics in Hypertension
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Gut Microbiome, Metabolome, and SSBP
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Recruiting
Salt Sensitivity Evaluation Via N-of-1 Trials (SENSE-Salt)
Salt-Sensitivity of Blood Pressure, Hypertension
Not yet recruitingPhase 2
Effect of an Isolevuglandin Scavenger on Salt Sensitivity of Blood Pressure and Immune Cell Activation in Humans
Salt Sensitivity of Blood Pressure, High Blood Pressure
RecruitingPhase 4
Forebrain Electroneutral Transporters in Salt-sensitive Hypertension: an MRI Study
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All Salt Sensitivity of Blood Pressure trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Central Sodium Sensing: Implications for Blood Pressure Regulation
ClinicalTrials.gov ID: NCT05480722
Acronym / sponsor ID: 1808532
Conditions: Salt Sensitivity of Blood Pressure
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: University of DelawareUniversity, hospital or other
Study start: 1 Jun 2022 (actual)
Primary completion: 31 Jan 2025 (actual)
Study completion: 31 Jan 2025 (actual)
First posted: 29 Jul 2022 (actual)
Results: Posted 8 Dec 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Crossover
Masking: Single blind (participant)
Number of arms: 2
Model description: single blinded crossover design

Arm	Type	Receives
Hypernatremia + Furosemide first, then Hypernatremia without Furosemide	Experimental	Other: Hypertonic Saline with furosemide, Other: Hypertonic Saline without furosemideParticipants 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.
Hypernatremia without Furosemide first, then Hypernatremia + Furosemide	Experimental	Other: Hypertonic Saline with furosemide, Other: Hypertonic Saline without furosemideParticipants 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.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Age: 18 - 45 years
Blood pressure: >100/60 mmHg and <130/80 mmHg
BMI: 18.5 kg/m2 - 30 kg/m2
Serum potassium: 3.5 mmol/L - 5.5 mmol/L

Key exclusion criteria (15 listed)

Age: < 18 years or > 45 years
Blood pressure: < 100/60 mmHg or > 130/80 mmHg
BMI: < 18.5 kg/m2 or > 30 kg/m2
Serum potassium: < 3.5 mmol/L or > 5.5 mmol/L
Abnormal ECG

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
Hypertonic Saline with furosemideSubjects will undergo MRI with a hypertonic saline infusion with NKCC2 antagonism (furosemide). 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.	Other	Hypernatremia + Furosemide first, then Hypernatremia without Furosemide, Hypernatremia without Furosemide first, then Hypernatremia + Furosemide
Hypertonic Saline without furosemideSubjects will undergo MRI with a hypertonic saline infusion. The hypertonic saline will be a 3% NaCl solution infused intravenously at a rate of 0.15 ml/kg/min for 30 minutes.	Other	Hypernatremia + Furosemide first, then Hypernatremia without Furosemide, Hypernatremia without Furosemide first, then Hypernatremia + Furosemide

Primary outcome

Functional Connectivity Between the Subfornical Organ and Organum Vasculosum of the Lamina Terminalis (Z-score)
Time frame: Functional connectivity (FC) was calculated at baseline (~10 min). Then, participants received a 30-minute hypertonic saline infusion (HSI) with or without furosemide before. FC was calculated during the early (0-15 min) and late phase (15-30 min) of HSI.
Functional connectivity between sodium sensing circumventricular organs (subfornical organ (SFO) and organum vasculosum of the lamina terminalis(OVLT)) was calculated (expressed as the z-score). Functional connectivity is a measure of the the correlation (or synchronization) of the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal time course between two brain regions. Pearson correlations were computed between the BOLD fMRI signal in the SFO and OVLT in a seed-to-seed functional connectivity analysis. Pearson correlations were converted to Z-scores using a Fisher's transform. A Z-score of 0 indicates no correlation between the BOLD fMRI signal between these 2 brain regions; a higher score indicates a greater, positive correlation between the BOLD fMRI signal in these 2 brain regions; a lower score indicates a greater, negative correlation between the fMRI signal in these 2 brain regions. This data does not have any clinical thresholds.

Results and safety

Results posted to the registry on 8 Dec 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Hypernatremia + Furosemide First, Then Hypernatremia Without Furosemide	9	4
Hypernatremia Without Furosemide First, Then Hypernatremia + Furosemide	3	2

Primary outcome: Functional Connectivity Between the Subfornical Organ and Organum Vasculosum of the Lamina Terminalis (Z-score)

Time frame: Functional connectivity (FC) was calculated at baseline (~10 min). Then, participants received a 30-minute hypertonic saline infusion (HSI) with or without furosemide before. FC was calculated during the early (0-15 min) and late phase (15-30 min) of HSI.. Mean (Standard Deviation). Unit: z-score

Measure	Hypertonic Saline Infusion Without Furosemide n = 6	Hypertonic Saline Infusion + Furosemide n = 6
Baseline (Immediately pre-furosemide and/or hypertonic saline infusion)	0.258490 (0.105129)	0.359145 (0.268795)
Early Phase (0-15 minutes of hypertonic saline infusion)	0.207372 (0.196048)	0.169055 (0.169819)
Late Phase (15-30 minutes of hypertonic saline infusion)	0.272881 (0.130301)	0.097043 (0.066845)

Adverse events

Time frame: From participant's initial enrollment through their study completion, an average of about 3 months for each participant.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Hypernatremia + Furosemide	0 of 12 (0%)	0 of 12 (0%)	0 of 12
Hypernatremia Without Furosemide	0 of 12 (0%)	0 of 12 (0%)	0 of 12

Limitations and caveats (from the sponsor): The study is limited by small sample size; the SFO and OVLT are small regions of interest, making accurate identification challenging; and a small number of participants completed the furosemide protocol, due to needing to urinate, making identification of the mechanism of sodium sensing difficult. The diet component of the protocol originally planned was made optional and few completed it due to the challenges of administering furosemide. We were unable to measure plasma vasopressin (AVP).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Data will be shared upon reasonable request.

Related trials for Salt Sensitivity of Blood Pressure

Not yet recruiting
Beta-2 Adrenergic Receptor Polymorphic Variants: An Endotype of Salt Sensitive Hypertension (Beta2AR).
Genetics in Hypertension
Not yet recruiting
Gut Microbiome, Metabolome, and SSBP
Salt-sensitivity of Blood Pressure
Recruiting
Salt Sensitivity Evaluation Via N-of-1 Trials (SENSE-Salt)
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Effect of an Isolevuglandin Scavenger on Salt Sensitivity of Blood Pressure and Immune Cell Activation in Humans
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RecruitingPhase 4
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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.

William B Farquhar, PhD principal investigator

University of Delaware

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Hypertonic Saline with furosemide and Hypertonic Saline without furosemide in people with Salt Sensitivity of Blood Pressure, run by University of Delaware 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 4 inclusion and 15 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 8 Dec 2025. 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 2025). 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?

Functional Connectivity Between the Subfornical Organ and Organum Vasculosum of the Lamina Terminalis (Z-score) (time frame: Functional connectivity (FC) was calculated at baseline (~10 min). Then, participants received a 30-minute hypertonic saline infusion (HSI) with or without furosemide before. FC was calculated during the early (0-15 min) and late phase (15-30 min) of HSI.). 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 NCT05480722.

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 8 Dec 2025.