Salt Sensitivity of Blood PressureNCT04258332
CARDIA-Salt Sensitivity of Blood Pressure (SSBP)
A study testing High Salt Diet and Low Salt Diet in people with Salt Sensitivity of Blood Pressure and Hypertension, run by Vanderbilt University Medical Center at 2 sites in United States.
Trial summary
Salt sensitivity of blood pressure (SSBP) is defined as the change in blood pressure (BP) in relation to change in salt intake. An increase in BP from low- to high-salt diet is common and associated with an increased risk of cardiovascular morbidity and mortality, even among normotensive individuals. Read more about this study
- Who is it for?
- Ages 50 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Salt Sensitivity of Blood Pressure, Hypertension
- What is being tested?
- High Salt Diet and Low Salt Diet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 281 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 May 2021to 17 May 2025
- Phase
- Interventional
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Potentially eligible individuals must consent to and be willing to adhere to the study protocol. We will include individuals not taking anti-HTN medications, i.e. normotensives and untreated hypertensives, and individuals with controlled HTN by use of ≤ 3 anti-HTN medications.
Who cannot join
- Unwilling to adhere to the study protocol
- Resistant HTN, defined as taking ≥ 4 anti-HTN medications to control BP or uncontrolled BP despite ≥ 3 anti-HTN medications that includes a diuretic
- Contraindications to high- or low-salt diet (e.g. heart, renal, or liver failure, postural orthostatic tachycardia syndrome)
- Use of salt tabs, fludricortisone, midodrine
- Contraindications to 24hr ABPM: bilateral upper extremity lymphedema, cuff will not fit
- Medical contraindications to foods, e.g. celiac disease, nut allergy, egg allergy, etc.
Show all 10Show fewer
- Year 35 core exam systolic BP < 90 or > 160 mm Hg or diastolic BP < 50 or > 100 mm Hg
- Current use of steroids, NSAIDS, anti-inflammatories
- Rheumatologic condition (e.g. Lupus, Rheumatoid Arthritis, Psoriatic arthritis, Inflammatory Bowel Disease, Multiple Sclerosis
- Immune deficiency or immunosuppressed
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Alabama Birmingham
Birmingham, Alabama, 35294
Northwestern University
Chicago, Illinois, 60611
About this study
Official title: Dietary Sodium Inflammation and Salt Sensitivity of Blood Pressure
Salt sensitivity of blood pressure (SSBP) is defined as the change in blood pressure (BP) in relation to change in salt intake. An increase in BP from low- to high-salt diet is common and associated with an increased risk of cardiovascular morbidity and mortality, even among normotensive individuals. Yet, the pathophysiology of SSBP is not well understood. The prevailing paradigm is that abnormalities of neurohormones that regulate sodium (Na+) retention and excretion and/or Na+ transporting pathways create Na+ imbalances that underlie susceptibility to SSBP. As a homeostatic mechanism, BP fluctuates to maintain Na+ balance, i.e. higher BP is needed for pressure natriuresis to excrete excess Na+. An alternate framework emphasizes vascular dysregulation as the inciting mechanism. In both constructs, how Na+ itself influences BP remains incompletely understood. Our preliminary work suggests that excess Na+ induces a pro-inflammatory state that sustains higher BP. Interleukin-6 (IL-6) drives the induction of interleukin-17 (IL-17) secreting T helper 17 cells that were recently demonstrated to be pathogenic in response to Na+ exposure. IL-6, IL-17 and related cytokines regulate renal Na+ transporters and raise BP through vascular inflammation, fibrosis, and impaired vasodilation. The immune response to high- and low-salt diet in humans, however, is not completely understood, emphasizing the need for more detailed human studies, with deeper immune profiling under controlled salt conditions and with neurohormonal assessment. Our overarching postulate is that the inflammatory response to excess dietary salt intake is associated with SSBP. The Coronary Artery Risk Development in Young Adults (CARDIA) study is the ideal cohort in which to translate our preliminary findings. Investigators propose to investigate SSBP in CARDIA using standardized low- and high-salt diets and 24-hour ambulatory BP monitoring. Investigators will quantify SSBP in a total of 500 participants from the Chicago and Birmingham field centers during the upcoming year 35 exam (beginning in 2020). Our specific aims are: 1) to define the distribution of SSBP and its clinical correlates in a contemporary community-based US cohort of middle-aged individuals; 2) to investigate the immune response to dietary salt loading, and 3) to investigate the association between the immune and BP responses to dietary salt loading. The proposed study represents a unique opportunity to leverage a large, well-phenotyped cohort to test novel hypotheses regarding SSBP. Phenotyping SSBP using standardized high- and low-salt diets in CARDIA will be novel as this has never been performed in any of the existing US based NHLBI sponsored cardiovascular epidemiologic cohorts. The proposed work has the potential to yield a more readily available approach for differentiating an individual as salt-sensitive or resistant. New insights into the pathophysiology of SSBP should also provide a foundation for investigating high-impact clinical applications, by informing future studies of therapies directed at SSBP. The scientific rigor is further enhanced by the rich clinical, genetic, and biochemical data available in CARDIA.
- Conditions
- Salt Sensitivity of Blood Pressure, Hypertension
- Being tested
- High Salt Diet, Low Salt Diet
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Salt DietDietary supplement
Patients will be randomized to be on a high salt diet for 7 days.
Low Salt DietDietary supplement
Patients will be randomized to be on a low salt for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| High Salt Diet then Low Salt Diet | Other | The high-salt diet will be achieved through the supplementation of each participant's usual diet with Na+ bullion packets (2 packets per day). This will increase Na+ intake by approximately 2,200 mg (≈100 mEq Na+) to a total greater than 5,000 mg Na+ per day based on prior estimates of Na+ intake (see section C1.2). In addition, 1,000 mg of calcium carbonate (provided via Tums tablets) will be taken daily on the high Na+ diet to reduce the potential impact of changes in calcium intake on blood pressure.
The low-salt diet is comprised of 7 days of freshly prepared frozen meals, snacks, and Na+ free water. All low-salt meals will be prepared in each site's Metabolic Kitchen, with standardization of diets across sites. The low-salt diet includes: 20 mEq Na+ (±2 mEq) (460 mg/day), 100 mEq potassium (±2 mEq), and 1,000 mg calcium (±50 mg). Receives: Dietary Supplement: High Salt Diet; Dietary Supplement: Low Salt Diet |
| Low Salt Diet then High Salt Diet | Other | The low-salt diet is comprised of 7 days of freshly prepared frozen meals, snacks, and Na+ free water. All low-salt meals will be prepared in each site's Metabolic Kitchen, with standardization of diets across sites. The low-salt diet includes: 20 mEq Na+ (±2 mEq) (460 mg/day), 100 mEq potassium (±2 mEq), and 1,000 mg calcium (±50 mg).
The high-salt diet will be achieved through the supplementation of each participant's usual diet with Na+ bullion packets (2 packets per day). This will increase Na+ intake by approximately 2,200 mg (≈100 mEq Na+) to a total greater than 5,000 mg Na+ per day based on prior estimates of Na+ intake (see section C1.2). In addition, 1,000 mg of calcium carbonate (provided via Tums tablets) will be taken daily on the high Na+ diet to reduce the potential impact of changes in calcium intake on blood pressure. Receives: Dietary Supplement: High Salt Diet; Dietary Supplement: Low Salt Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Salt Sensitivity of Blood Pressure
The change in 24-hour ambulatory mean arterial pressure (MAP) following one week of high-salt and following one week of low-salt diet. This is calculated as the 24 hour ambulatory MAP on the high-salt diet minus the 24 hour ambulatory MAP on the low-salt diet.
Measured: 14 days total which is 7 days each of high- and low-salt diet
Immune Response to Dietary Salt Loading, Change in Circulating Levels of IL-6
The change in circulating levels of interleukin-6 (IL-6) following one week of high-salt and following one week of low-salt diet. This is calculated as the IL-6 level on the high-salt diet minus the IL-6 level on the low-salt diet.
Measured: 14 days total which is 7 days each of high- and low-salt diet
Immune Response to Dietary Salt Loading, Change in Circulating Levels of IL-17
The change in circulating levels of interleukin-17 (IL-17) following one week of high-salt and following one week of low-salt diet. This is calculated as the IL-17 level on the high-salt diet minus the IL-17 level on the low-salt diet.
Measured: 14 days total which is 7 days each of high- and low-salt diet
Immune Response to Dietary Salt Loading, IL-10, Change in Circulating Levels of IL-10
The change in circulating levels of interleukin-10 (IL-10) following one week of high-salt and following one week of low-salt diet. This is calculated as the IL-10 level on the high-salt diet minus the IL-10 level on the low-salt diet.
Measured: 14 days total which is 7 days each of high- and low-salt diet
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study start17 May 2021
- Primary completion17 May 2025
- Study completion17 May 2025
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 (1)Papers the sponsor has linked to this study.
- Other trials for Salt Sensitivity of Blood PressureStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 281 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Northwestern University, University of Alabama at Birmingham
- Responsible party
- Principal investigator, Deepak Gupta, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04258332
- Sponsor's protocol ID
- 190622
- Status last verified
- Jun 2026
- First submitted
- 4 Feb 2020
- Last updated
- 7 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Research data will be shared according to the most recent NIH guideline. The data collected will be made available by the CARDIA Data Coordinating Center (DCC) both to the study for use by other investigators and to NHLBI for inclusion in the NHLBI's Data Repository Program, in accordance with the NHLBI Policy for Data Sharing from Clinical Trials and Epidemiological Studies, http://www.nhlbi.nih.gov/funding/datasharing.htm. Through the conduct of the study and in resource sharing, attention will be given to protect private health information; thus, we will make data available to others through the CARDIA DCC under a data use agreement specifying (1) to use the data only for research purposes and not to identify an individual participant; (2) to secure the data using appropriate computer technology; and (3) to destroy or return the data after analyses are completed. The overall CARDIA DCC at the UAB will be responsible for overseeing approval and sharing of research data.
Publications
Gupta DK, Lewis CE, Varady KA, Su YR, Madhur MS, Lackland DT, Reis JP, Wang TJ, Lloyd-Jones DM, Allen NB. Effect of Dietary Sodium on Blood Pressure: A Crossover Trial. JAMA. 2023 Dec 19;330(23):2258-2266. doi: 10.1001/jama.2023.23651.
PubMed 37950918
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Sodium Inflammation and Salt Sensitivity of Blood Pressure
- ClinicalTrials.gov ID
- NCT04258332
- Acronym / sponsor ID
- 190622
- Conditions
- Salt Sensitivity of Blood Pressure, Hypertension
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 281 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Northwestern University, University of Alabama at Birmingham
- Study start
- 17 May 2021 (actual)
- Primary completion
- 17 May 2025 (actual)
- Study completion
- 17 May 2025 (actual)
- First posted
- 6 Feb 2020 (actual)
- Results
- Posted 7 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Salt sensitivity of blood pressure (SSBP) is defined as the change in blood pressure (BP) in relation to change in salt intake. An increase in BP from low- to high-salt diet is common and associated with an increased risk of cardiovascular morbidity and mortality, even among normotensive individuals. Yet, the pathophysiology of SSBP is not well understood. The prevailing paradigm is that abnormalities of neurohormones that regulate sodium (Na+) retention and excretion and/or Na+ transporting pathways create Na+ imbalances that underlie susceptibility to SSBP. As a homeostatic mechanism, BP fluctuates to maintain Na+ balance, i.e. higher BP is needed for pressure natriuresis to excrete excess Na+. An alternate framework emphasizes vascular dysregulation as the inciting mechanism. In both constructs, how Na+ itself influences BP remains incompletely understood. Our preliminary work suggests that excess Na+ induces a pro-inflammatory state that sustains higher BP. Interleukin-6 (IL-6) drives the induction of interleukin-17 (IL-17) secreting T helper 17 cells that were recently demonstrated to be pathogenic in response to Na+ exposure. IL-6, IL-17 and related cytokines regulate renal Na+ transporters and raise BP through vascular inflammation, fibrosis, and impaired vasodilation. The immune response to high- and low-salt diet in humans, however, is not completely understood, emphasizing the need for more detailed human studies, with deeper immune profiling under controlled salt conditions and with neurohormonal assessment. Our overarching postulate is that the inflammatory response to excess dietary salt intake is associated with SSBP. The Coronary Artery Risk Development in Young Adults (CARDIA) study is the ideal cohort in which to translate our preliminary findings. Investigators propose to investigate SSBP in CARDIA using standardized low- and high-salt diets and 24-hour ambulatory BP monitoring. Investigators will quantify SSBP in a total of 500 participants from the Chicago and Birmingham field centers during the upcoming year 35 exam (beginning in 2020). Our specific aims are: 1) to define the distribution of SSBP and its clinical correlates in a contemporary community-based US cohort of middle-aged individuals; 2) to investigate the immune response to dietary salt loading, and 3) to investigate the association between the immune and BP responses to dietary salt loading. The proposed study represents a unique opportunity to leverage a large, well-phenotyped cohort to test novel hypotheses regarding SSBP. Phenotyping SSBP using standardized high- and low-salt diets in CARDIA will be novel as this has never been performed in any of the existing US based NHLBI sponsored cardiovascular epidemiologic cohorts. The proposed work has the potential to yield a more readily available approach for differentiating an individual as salt-sensitive or resistant. New insights into the pathophysiology of SSBP should also provide a foundation for investigating high-impact clinical applications, by informing future studies of therapies directed at SSBP. The scientific rigor is further enhanced by the rich clinical, genetic, and biochemical data available in CARDIA.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Salt Diet then Low Salt Diet | Other | Dietary Supplement: High Salt Diet, Dietary Supplement: Low Salt DietThe high-salt diet will be achieved through the supplementation of each participant's usual diet with Na+ bullion packets (2 packets per day). This will increase Na+ intake by approximately 2,200 mg (≈100 mEq Na+) to a total greater than 5,000 mg Na+ per day based on prior estimates of Na+ intake (see section C1.2). In addition, 1,000 mg of calcium carbonate (provided via Tums tablets) will be taken daily on the high Na+ diet to reduce the potential impact of changes in calcium intake on blood pressure. The low-salt diet is comprised of 7 days of freshly prepared frozen meals, snacks, and Na+ free water. All low-salt meals will be prepared in each site's Metabolic Kitchen, with standardization of diets across sites. The low-salt diet includes: 20 mEq Na+ (±2 mEq) (460 mg/day), 100 mEq potassium (±2 mEq), and 1,000 mg calcium (±50 mg). |
| Low Salt Diet then High Salt Diet | Other | Dietary Supplement: High Salt Diet, Dietary Supplement: Low Salt DietThe low-salt diet is comprised of 7 days of freshly prepared frozen meals, snacks, and Na+ free water. All low-salt meals will be prepared in each site's Metabolic Kitchen, with standardization of diets across sites. The low-salt diet includes: 20 mEq Na+ (±2 mEq) (460 mg/day), 100 mEq potassium (±2 mEq), and 1,000 mg calcium (±50 mg). The high-salt diet will be achieved through the supplementation of each participant's usual diet with Na+ bullion packets (2 packets per day). This will increase Na+ intake by approximately 2,200 mg (≈100 mEq Na+) to a total greater than 5,000 mg Na+ per day based on prior estimates of Na+ intake (see section C1.2). In addition, 1,000 mg of calcium carbonate (provided via Tums tablets) will be taken daily on the high Na+ diet to reduce the potential impact of changes in calcium intake on blood pressure. |
Who may qualify
- Ages
- 50 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Potentially eligible individuals must consent to and be willing to adhere to the study protocol. We will include individuals not taking anti-HTN medications, i.e. normotensives and untreated hypertensives, and individuals with controlled HTN by use of ≤ 3 anti-HTN medications.
Key exclusion criteria (10 listed)
- Unwilling to adhere to the study protocol
- Resistant HTN, defined as taking ≥ 4 anti-HTN medications to control BP or uncontrolled BP despite ≥ 3 anti-HTN medications that includes a diuretic
- Contraindications to high- or low-salt diet (e.g. heart, renal, or liver failure, postural orthostatic tachycardia syndrome)
- Use of salt tabs, fludricortisone, midodrine
- Contraindications to 24hr ABPM: bilateral upper extremity lymphedema, cuff will not fit
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 |
|---|---|---|
| High Salt DietPatients will be randomized to be on a high salt diet for 7 days. | Dietary supplement | High Salt Diet then Low Salt Diet, Low Salt Diet then High Salt Diet |
| Low Salt DietPatients will be randomized to be on a low salt for 7 days. | Dietary supplement | High Salt Diet then Low Salt Diet, Low Salt Diet then High Salt Diet |
Primary outcome
Salt Sensitivity of Blood Pressure
Time frame: 14 days total which is 7 days each of high- and low-salt diet
The change in 24-hour ambulatory mean arterial pressure (MAP) following one week of high-salt and following one week of low-salt diet. This is calculated as the 24 hour ambulatory MAP on the high-salt diet minus the 24 hour ambulatory MAP on the low-salt diet.
Immune Response to Dietary Salt Loading, Change in Circulating Levels of IL-6
Time frame: 14 days total which is 7 days each of high- and low-salt diet
The change in circulating levels of interleukin-6 (IL-6) following one week of high-salt and following one week of low-salt diet. This is calculated as the IL-6 level on the high-salt diet minus the IL-6 level on the low-salt diet.
Immune Response to Dietary Salt Loading, Change in Circulating Levels of IL-17
Time frame: 14 days total which is 7 days each of high- and low-salt diet
The change in circulating levels of interleukin-17 (IL-17) following one week of high-salt and following one week of low-salt diet. This is calculated as the IL-17 level on the high-salt diet minus the IL-17 level on the low-salt diet.
Immune Response to Dietary Salt Loading, IL-10, Change in Circulating Levels of IL-10
Time frame: 14 days total which is 7 days each of high- and low-salt diet
The change in circulating levels of interleukin-10 (IL-10) following one week of high-salt and following one week of low-salt diet. This is calculated as the IL-10 level on the high-salt diet minus the IL-10 level on the low-salt diet.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37950918Gupta DK, Lewis CE, Varady KA, Su YR, Madhur MS, Lackland DT, Reis JP, Wang TJ, Lloyd-Jones DM, Allen NB. Effect of Dietary Sodium on Blood Pressure: A Crossover Trial. JAMA. 2023 Dec 19;330(23):2258-2266. doi: 10.1001/jama.2023.23651.
- Individual participant dataSharing planned: Yes. Research data will be shared according to the most recent NIH guideline. The data collected will be made available by the CARDIA Data Coordinating Center (DCC) both to the study for use by other investigators and to NHLBI for inclusion in the NHLBI's Data Repository Program, in accordance with the NHLBI Policy for Data Sharing from Clinical Trials and Epidemiological Studies, http://www.nhlbi.nih.gov/funding/datasharing.htm. Through the conduct of the study and in resource sharing, attention will be given to protect private health information; thus, we will make data available to others through the CARDIA DCC under a data use agreement specifying (1) to use the data only for research purposes and not to identify an individual participant; (2) to secure the data using appropriate computer technology; and (3) to destroy or return the data after analyses are completed. The overall CARDIA DCC at the UAB will be responsible for overseeing approval and sharing of research data.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High Salt Diet and Low Salt Diet in people with Salt Sensitivity of Blood Pressure and Hypertension, run by Vanderbilt University Medical Center at 2 sites 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 1 inclusion and 10 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 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2026). 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?
Salt Sensitivity of Blood Pressure (time frame: 14 days total which is 7 days each of high- and low-salt diet). The study lists 4 primary outcomes in all. 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 NCT04258332, which also lists 1 linked publication.
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 7 Jul 2026.