NCT02236520

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
71

participants targeted

Target at P25-P50 for phase_2 hypertension

Timeline
Completed

Started Sep 2014

Typical duration for phase_2 hypertension

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2014

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

September 8, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 10, 2014

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2018

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

May 22, 2019

Completed
Last Updated

May 22, 2019

Status Verified

April 1, 2019

Enrollment Period

3.7 years

First QC Date

September 8, 2014

Results QC Date

April 30, 2019

Last Update Submit

April 30, 2019

Conditions

Hypertension

Keywords

Na+ MRIsalt stores

Outcome Measures

Primary Outcomes (1)

  • 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

    baseline and 8 weeks

Study Arms (4)

Spironolactone

ACTIVE COMPARATOR

50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks

Drug: Spironolactone

Chlorthalidone

ACTIVE COMPARATOR

25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks

Drug: Chlorthalidone

Diet

ACTIVE COMPARATOR

diet of 6 g salt per day for 8 weeks

Dietary Supplement: Diet

Placebo

PLACEBO COMPARATOR

placebo capsule administered orally 1 per day for 8 weeks

Drug: Placebo

Interventions

SpironolactoneDRUG
Spironolactone
ChlorthalidoneDRUG
Chlorthalidone
DietDIETARY_SUPPLEMENT
Diet
PlaceboDRUG
Placebo

Eligibility Criteria

Age50 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (2)

  • Ertuglu LA, Sahinoz M, Alsouqi A, Deger SM, Guide A, Stewart TG, Pike M, Robinson-Cohen C, Akwo E, Pridmore M, Crescenzi R, Madhur MS, Harrison DG, Luft FC, Titze J, Ikizler TA. High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals. Nutr Metab Cardiovasc Dis. 2023 Jul;33(7):1398-1406. doi: 10.1016/j.numecd.2023.03.024. Epub 2023 Apr 10.

    PMID: 37156670DERIVED

  • 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.

    PMID: 35435017DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

SpironolactoneChlorthalidoneDiet

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

LactonesOrganic ChemicalsPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsBenzenesulfonamidesSulfonamidesAmidesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsBenzophenonesPhthalimidesImidesKetonesSulfonesSulfur CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsNutritional Physiological PhenomenaDiet, Food, and NutritionPhysiological Phenomena

Results Point of Contact

Title
Alp Ikizler
Organization
Vanderbilt University Medical Center
alp.ikizler@vumc.org
(615) 343-7592

Study Officials

  • Alp Ikizler, MD

    Vanderbilt University

    PRINCIPAL INVESTIGATOR

  • Jens Titze, MD

    Vanderbilt University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

September 8, 2014

First Posted

September 10, 2014

Study Start

September 1, 2014

Primary Completion

May 1, 2018

Study Completion

May 1, 2018

Last Updated

May 22, 2019

Results First Posted

May 22, 2019

Record last verified: 2019-04

Locations

US(1)