Tissue Sodium in Pre-hypertensive Patients
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Spironolactone; Chlorthalidone; Diet; Placebo
Intervention MeSH terms: Chlorthalidone; Spironolactone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 71.0
Sex: All
Minimum age: 50 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Na+ MRI; salt stores

Summary:

      Cardiovascular disease is the first common cause of death worldwide. Hypertension is the
      number one driving risk factor. Hypertension has long been associated with dietary salt
      intake. We believe that the accumulation of salt in the interstitium and inside cells
      represents a neglected risk factor, which initiates a pro-inflammatory state, chronically
      increases blood pressure, and leads to systemic energy imbalance. We will explore the concept
      that Na+ storage in the skin and in muscle is associated with increased blood pressure, a
      pro-inflammatory state, and reduced insulin sensitivity. We will do so by addressing the
      following specific aims:

        -  Specific Aim 1: To test the hypothesis that African Americans are characterized by
           increased tissue Na+ storage, which is paralleled by higher blood pressure, reduced
           forearm blood flow, and enhanced pulse wave velocity

        -  Specific Aim 2: To test the hypothesis that treatment with spironolactone reduces tissue
           Na+ content

        -  Specific Aim 3: To test the hypothesis that Na+ storage leads to immune cell activation

        -  Specific Aim 4: To test the hypothesis that the accumulation of salt in skin and muscle
           is associated with decreased insulin sensitivity and propensity to diabetes mellitus
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 30 to 80 years old;

          -  Systolic blood pressures between 110 to 150 mmHg and/or diastolic blood pressure
             between 80-99 mmHg;

          -  Ability to give informed consent.

        Exclusion Criteria:

          -  Pregnancy;

          -  Intolerance to study protocols;

          -  Acute cardiovascular events within the previous 6 months;

          -  Impaired renal function [estimated glomerular filtration rate (GFR) < 45
             ml/min/1.73m^2];

          -  Current or recent treatment with systemic glucocorticoid therapy (within 1 month of
             enrollment);

          -  Current use of anti-hypertensive medication (except calcium channel blockers and beta
             blockers);

          -  Diabetes mellitus requiring medical therapy;

          -  Morbid obesity (BMI > 45);

          -  Prior adverse reaction to a thiazide or spironolactone;

          -  Claustrophobia preventing the patient from having an MRI or other contraindications to
             MRI;

          -  Impaired hepatic function (aspartate amino transaminase and/or alanine amino
             transaminase > 1.5x upper limit of normal range);

          -  Current illicit drug use;

          -  Sexually active women of childbearing potential** who are unwilling to practice
             adequate contraception during the study [adequate contraceptive measures include
             stable use of oral contraceptives or other prescription pharmaceutical contraceptives
             for 2 or more menstrual cycles prior to screening; intrauterine device (IUD);
             bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly,
             or diaphragm plus contraceptive sponge, foam, or jelly].

               -  Postmenopausal women must be amenorrheic for at least 12 months in order not to
                  be considered of child bearing potential. Pregnancy testing and contraception are
                  not required for women with documented hysterectomy or tubal ligation.