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

Sponsor
University of Delaware (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06094816
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
120
Enrollment
2
Arms
54
Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Furosemide (Diuretic)
  • Other: Hypertonic Saline Infusion
 N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
Double blind randomized cross-overDouble blind randomized cross-over
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
Forebrain Electroneutral Transporters in Salt-sensitive Hypertension: an MRI Study
Anticipated Study Start Date :
Jan 1, 2024
Anticipated Primary Completion Date :
Jan 1, 2028
Anticipated Study Completion Date :
Jul 1, 2028

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Bold fMRI [1 hour]

      Intensity of sodium sensing regions of the brain

    Secondary Outcome Measures

    1. Blood Pressure [1 hour]

      Systolic and Diastolic Blood pressure responses to hypertonic saline

    Other Outcome Measures

    1. Sympathetic Nerve Activity [1 hour]

      sympathetic bursts per minute

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Age: > 40 years or < 60 years

    • Blood pressure: > 120/80 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: < 120/80 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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

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

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Delaware
    ClinicalTrials.gov Identifier:
    NCT06094816
    Other Study ID Numbers:
    • 2053776
    • R01HL163906
    First Posted:
    Oct 23, 2023
    Last Update Posted:
    Oct 23, 2023
    Last Verified:
    Oct 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Hypertension
    Furosemide
    Diuretics

    Study Results

    No Results Posted as of Oct 23, 2023