Clinical trial NCT02236520: Tissue Sodium in Pre-hypertensive Patients
Official title: Tissue Sodium in Pre-hypertensive Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Na+ MRI
salt stores
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2014-09-10
Enrollment: 71
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI)
timeFrame: baseline and 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Alp Ikizler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University
name: Jens Titze, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alsouqi A, Deger SM, Sahinoz M, Mambungu C, Clagett AR, Bian A, Guide A, Stewart TG, Pike M, Robinson-Cohen C, Crescenzi R, Madhur MS, Harrison DG, Ikizler TA. Tissue Sodium in Patients With Early Stage Hypertension: A Randomized Controlled Trial. J Am Heart Assoc. 2022 Apr 19;11(8):e022723. doi: 10.1161/JAHA.121.022723. Epub 2022 Apr 18.