CARDIA-Salt Sensitivity of Blood Pressure (SSBP)

Hypertension Clinical Trial

Official title:

Dietary Sodium Inflammation and Salt Sensitivity of Blood Pressure

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04258332
• Other study ID #: 190622
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 17, 2021
• Est. completion date: May 31, 2025

Study information

• Verified date: June 2024
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 70 Years

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

• 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.

• 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

Related Conditions & MeSH terms

• Hypersensitivity
• Hypertension
• Salt Sensitivity of Blood Pressure

Intervention

Dietary Supplement:
• High Salt Diet
Patients will be randomized to be on a high salt diet for 7 days.
• Low Salt Diet
Patients will be randomized to be on a low salt for 7 days.

Locations

Country	Name	City	State
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Northwestern University	Chicago	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	Northwestern University, University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Salt sensitivity of blood pressure	The change in 24-hour ambulatory mean arterial pressure (MAP) from one week of high-salt to one week of low-salt diet	14 days
Primary	Immune response to dietary salt loading, IL-6	Circulating levels of IL-6	14 days
Primary	Immune response to dietary salt loading, Change in circulating levels of IL-17	Circulating levels of IL-17	14 days
Primary	Immune response to dietary salt loading, IL-10	Circulating levels of IL-10	14 days