Hypertension
Conditions
Keywords
Na+ MRI, salt stores
Brief 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
Interventions
DRUGSpironolactone
DRUGChlorthalidone
DIETARY_SUPPLEMENTDiet
DRUGPlacebo
Sponsors
American Heart Association
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI) | baseline and 8 weeks | NaMRI is a sensitive laboratory assessment of the concentration of sodium in tissue |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Spironolactone 50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks
Spironolactone | 16 |
| Chlorthalidone 25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks
Chlorthalidone | 13 |
| Diet diet of 6 g salt per day for 8 weeks
Diet | 15 |
| Placebo placebo capsule administered orally 1 per day for 8 weeks
Placebo | 15 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 5 | 0 | 0 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Spironolactone | Total | Placebo | Diet | Chlorthalidone |
|---|---|---|---|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 11 | 48 years STANDARD_DEVIATION 12 | 48 years STANDARD_DEVIATION 14 | 49 years STANDARD_DEVIATION 13 | 49 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 58 Participants | 15 Participants | 15 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 26 Participants | 6 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 33 Participants | 9 Participants | 7 Participants | 8 Participants |
| Region of Enrollment United States | 16 participants | 59 participants | 15 participants | 15 participants | 13 participants |
| Sex: Female, Male Female | 11 Participants | 40 Participants | 10 Participants | 9 Participants | 10 Participants |
| Sex: Female, Male Male | 5 Participants | 19 Participants | 5 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 13 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 4 / 16 | 2 / 13 | 1 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 13 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI)
NaMRI is a sensitive laboratory assessment of the concentration of sodium in tissue
Time frame: baseline and 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Spironolactone | Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI) | -0.202 mmol/L |
| Chlorthalidone | Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI) | 0.430 mmol/L |
| Diet | Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI) | -1.745 mmol/L |
| Placebo | Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI) | -0.407 mmol/L |