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

NCT ID: NCT06094816

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-05
• Study Completion Date: 2028-07-31

Brief Summary

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.

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.

Conditions

Salt-Sensitivity of Blood Pressure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Salt Sensitive

Adults who experience increased BP (mean arterial pressures \>5mmHg) during dietary sodium challenge

Group Type: EXPERIMENTAL

Furosemide (Diuretic)

Intervention Type: DRUG

The diuretic furosemide will be given during a 3% hypertonic saline infusion to examine blockade of the NKCC2.

Hypertonic Saline Infusion

Intervention Type: OTHER

3% Hypertonic saline infusion to acutely increase sodium and osmolality

Salt Resistant Adults

Adults who experience minimal BP change during dietary sodium challenge

Group Type: EXPERIMENTAL

Furosemide (Diuretic)

Intervention Type: DRUG

The diuretic furosemide will be given during a 3% hypertonic saline infusion to examine blockade of the NKCC2.

Hypertonic Saline Infusion

Intervention Type: OTHER

3% Hypertonic saline infusion to acutely increase sodium and osmolality

Interventions

Furosemide (Diuretic)

The diuretic furosemide will be given during a 3% hypertonic saline infusion to examine blockade of the NKCC2.

Intervention Type: DRUG

Hypertonic Saline Infusion

3% Hypertonic saline infusion to acutely increase sodium and osmolality

Intervention Type: OTHER

Other Intervention Names

Lasix

Eligibility Criteria

Inclusion 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
• 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Delaware

OTHER

Sponsor Role: lead

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Delaware

Newark, Delaware, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Megan Wenner, PhD

Role: CONTACT

mwenner@udel.edu

3028317343

Virginia Nuckols, PhD

Role: CONTACT

gnuckols@udel.edu

Facility Contacts

Ginny Nuckols, PhD

Role: primary

gnuckols@udel.edu

Katherine Masso, BS

Role: backup

kcmasso@udel.edu

Other Identifiers

R01HL163906

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2053776

Identifier Type: -

Identifier Source: org_study_id