Forebrain Electroneutral Transporters in Salt-sensitive Hypertension: an MRI Study

The overall objective of this project is to identify the key salt-sensing regions of the brain and determine the underlying mechanism of sodium sensing. The investigators will assess how the brain responds to an acute increase of salt in the blood using MRI. This will be done during a 30-minute infusion of a saline solution containing 3% salt. One trial will be conducted with a salt sensing channel blocker and one trial without the salt sensing channel blocker. This will help to assess the role of a specific salt sensing channel in the brain. Salt sensitivity of BP will be assessed using 7-day dietary feeding where participants will be given food to consume for 7-days. Comparisons will be made between salt resistant (no change in blood pressure going from low to high salt diets) and salt sensitive adults (a change in blood pressure going from low to high salt diets). The investigators think the changes in MRI will be greater in salt sensitive compared to salt resistant subjects.

Study Overview

• Status: Recruiting
• Conditions: Salt-Sensitivity of Blood Pressure
• Intervention / Treatment: Drug: Furosemide (Diuretic); Other: Hypertonic Saline Infusion

Detailed Description

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 middle-aged men and women with high blood pressure and determine if the Na-K-2Cl co-transporter (NKCC2) mediates the neurohumoral response to acute hypernatremia. The investigators plan on comparing these central sodium responses to acute hypernatremia between salt-sensitive and salt-resistant adults. In this randomized double-blinded crossover study subjects will have a 3% NaCl (hypertonic saline) infusion with or without NKCC2 antagonism (furosemide). Completion of this project will increase the understanding of blood pressure regulation, which has major public health implications.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Megan Wenner, PhD; Phone Number: 3028317343; Email: mwenner@udel.edu
• Study Contact Backup: Name: Virginia Nuckols, PhD; Email: gnuckols@udel.edu

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • Recruiting
      • University of Delaware
      • Contact: Ginny Nuckols, PhD; Email: gnuckols@udel.edu
      • Contact: Katherine Masso, BS; Email: kcmasso@udel.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age: > 40 years or < 60 years
• Blood pressure: > 100/60 mmHg or < 140/90 mmHg
• BMI: > 18.5 kg/m2 or < 35 kg/m2
• Serum potassium: > 3.5 mmol/L or < 5.5 mmol/L
• No history of cardiovascular, renal, metabolic, or neurological disease

Exclusion Criteria:

• Age: < 40 years or > 60 years
• Blood pressure: < 100/60 mmHg or > 140/90 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
• Contra-indications to MRI (implants, metal, etc)
• Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Salt Resistant Adults; Adults who experience minimal BP change during dietary sodium challenge	Drug: Furosemide (Diuretic); The diuretic furosemide will be given during a 3% hypertonic saline infusion to examine blockade of the NKCC2.; Other Names: Lasix; Other: Hypertonic Saline Infusion; 3% Hypertonic saline infusion to acutely increase sodium and osmolality
Experimental: Salt Sensitive; Adults who experience increased BP (mean arterial pressures >5mmHg) during dietary sodium challenge	Drug: Furosemide (Diuretic); The diuretic furosemide will be given during a 3% hypertonic saline infusion to examine blockade of the NKCC2.; Other Names: Lasix; Other: Hypertonic Saline Infusion; 3% Hypertonic saline infusion to acutely increase sodium and osmolality

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bold fMRI	Intensity of sodium sensing regions of the brain	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	Systolic and Diastolic Blood pressure responses to hypertonic saline	1 hour

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sympathetic Nerve Activity	sympathetic bursts per minute	1 hour

Collaborators and Investigators

• Sponsor: University of Delaware
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 17, 2023
• First Posted (Actual): October 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Natriuretic Agents; Sulfur Compounds; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Amides; Aniline Compounds; Amines; Sulfonamides; Sulfanilamides; Sulfones; Furosemide; Diuretics
• Other Study ID Numbers: 2053776; R01HL163906 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No