Central Sodium Sensing: Implications for Blood Pressure Regulation

NCT05480722 | Completed Results

• 1 other identifier: 1808532
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Salt Sensitivity of Blood Pressure

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Study Arms (2)

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.

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.

Other: Hypertonic Saline with furosemide; Other: Hypertonic Saline without furosemide

Interventions

Hypertonic Saline with furosemide OTHER

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.

Hypernatremia + Furosemide first, then Hypernatremia without Furosemide; Hypernatremia without Furosemide first, then Hypernatremia + Furosemide

Hypertonic Saline without furosemide OTHER

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.

Hypernatremia + Furosemide first, then Hypernatremia without Furosemide; Hypernatremia without Furosemide first, then Hypernatremia + Furosemide

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Delaware: lead

Study Sites (1)

William B Farquhar

Newark, Delaware, 19713, United States

Location

MeSH Terms

Interventions

Saline Solution, Hypertonic; Furosemide

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Limitations and Caveats

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).

Results Point of Contact

• Title: William B Farquhar
• Organization: University of Delaware

wbf@udel.edu

302-831-6168

Study Officials

• William B Farquhar, PhD

  University of Delaware

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: single blinded
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: single blinded crossover design

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: July 29, 2022
• Study Start: June 1, 2022
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: December 8, 2025
• Results First Posted: December 8, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Immediately
• Access Criteria: Upon reasonable request

Locations

US (1)