HypertensionPhase 2NCT02236520
Tissue Sodium in Pre-hypertensive Patients
A Phase 2 study testing Spironolactone, Chlorthalidone and Diet in people with Hypertension, run by Vanderbilt University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- Spironolactone, Chlorthalidone and Diet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to 1 May 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
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
- Conditions
- Hypertension
- Being tested
- Spironolactone, Chlorthalidone, Diet, Placebo
- Keywords
- Na+ MRI, salt stores
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
ChlorthalidoneDrug
DietDietary supplement
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Active comparator | 50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks Receives: Drug: Spironolactone |
| Chlorthalidone | Active comparator | 25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks Receives: Drug: Chlorthalidone |
| Diet | Active comparator | diet of 6 g salt per day for 8 weeks Receives: Dietary Supplement: Diet |
| Placebo | Placebo comparator | placebo capsule administered orally 1 per day for 8 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion1 May 2018
- Study completion1 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Principal investigator, Alp Ikizler, Vanderbilt University Medical Center
- Investigators
- Alp Ikizler, MD, Principal investigator, Vanderbilt UniversityJens Titze, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02236520
- Sponsor's protocol ID
- 141382
- Status last verified
- Apr 2019
- First submitted
- 8 Sep 2014
- Last updated
- 22 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 37156670Alsouqi 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.
PubMed 35435017
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tissue Sodium in Pre-hypertensive Patients
- ClinicalTrials.gov ID
- NCT02236520
- Acronym / sponsor ID
- 141382
- Conditions
- Hypertension
- Keywords
- Na+ MRI, salt stores
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- Sep 2014 (actual)
- Primary completion
- 1 May 2018 (actual)
- Study completion
- 1 May 2018 (actual)
- First posted
- 10 Sep 2014 (estimated)
- Results
- Posted 22 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Active comparator | Drug: Spironolactone50 mg capsule of Spironolactone administered orally 1 per day for 8 weeks |
| Chlorthalidone | Active comparator | Drug: Chlorthalidone25 mg capsule of Chlorthalidone administered orally 1 per day for 8 weeks |
| Diet | Active comparator | Dietary Supplement: Dietdiet of 6 g salt per day for 8 weeks |
| Placebo | Placebo comparator | Drug: Placeboplacebo capsule administered orally 1 per day for 8 weeks |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (14 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spironolactone | Drug | Spironolactone |
| Chlorthalidone | Drug | Chlorthalidone |
| Diet | Dietary supplement | Diet |
| Placebo | Drug | Placebo |
Primary outcome
Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI)
Time frame: baseline and 8 weeks
NaMRI is a sensitive laboratory assessment of the concentration of sodium in tissue
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37156670Ertuglu 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.
- Derived from this study: PubMed 35435017Alsouqi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alp Ikizler, MD principal investigator
Vanderbilt University
Jens Titze, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Spironolactone, Chlorthalidone and Diet in people with Hypertension, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Tissue Sodium Concentration Measured Using Sodium Magnetic Resonance Imaging (NaMRI) (time frame: baseline and 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02236520, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2019.