Visualizing Vascular Mechanisms of Salt Sensitivity

This study aims to assess the salt sensitive blood pressure response to dietary salt load compared with radiological markers of salt handling.

Study Overview

• Status: Completed
• Conditions: Obesity; Cardiovascular Risk Factor; Salt; Excess
• Intervention / Treatment: Dietary supplement: Low-salt diet; Dietary supplement: High-salt diet

Detailed Description

Hypertension is a major cause of heart disease, heart failure, and stroke. Hypertension, or high blood pressure, affects people differently and is related to the body's ability to maintain healthy circulation of salt. Some individuals may be affected by salt sensitive blood pressure (SSBP), when their blood pressure changes in response to dietary salt load. SSBP is a prevalent, independent risk factor for developing cardiovascular disease that preferentially affects black individuals. Current methods to assess SSBP require dietary salt loading over the course of days to weeks, and measurement of blood pressure following high salt diet and low salt diet. Such lengthy protocols are not feasible in a clinical setting to evaluate this risk factor for cardiovascular disease, and more importantly, these procedures provide incomplete information about mechanisms of salt sensitivity.

Our knowledge regarding salt handling in the body is limited. While renal dysfunction is partly responsible for SSBP, recent research points to the role of lymphatic vascular clearance in regulating tissue salt storage and blood pressure control. To better understand these mechanisms in vivo, we have recently developed a noninvasive magnetic resonance (MR) lymphangiography method sensitive to lymphatic vasculature, and applied standardized MR protocols for measuring tissue sodium and fat storage in adults with impaired lymphatic clearance. We found evidence of lymph stasis and tissue salt deposition that correlated with local subcutaneous fat volume. Here, we will test whether similar lymphatic pathways are impaired in persons with SSBP, leading to tissue salt and fat storage, in comparison to the involvement of renal dysfunction in SSBP tissue profiles.

The aims of this study are to improve our understanding of vascular mechanisms of human salt storage, and to provide standardized radiologic biomarkers sensitive to the SSBP phenotype. This study will test the primary hypothesis that the SSBP response is correlated with baseline tissue sodium storage, and elevated in persons with salt sensitivity. Secondary hypotheses will address whether the SSBP response is related to fat storage, lymphatic vascular function, renal vascular function, and impaired target organ responses to salt loading, including decreased urinary sodium excretion, and less suppression of plasma renin and serum aldosterone.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Karlis Draulis, BS; Phone Number: 615-875-6028; Email: karlis.j.draulis@vumc.org
• Study Contact Backup: Name: Cassandra Reynolds, BS, CCRC; Phone Number: 615-875-9854; Email: cassandra.f.reynolds@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Identification as black race
• Age between 18 and 55 years
• Body mass index between 25 and <35 kg/m2
• Normotensive or pre-hypertensive
• Willing to adhere to study diets
• Able to provide informed consent and communicate with study personnel

Exclusion Criteria:

• Prevalent cardiovascular disease or use of medications for cardiovascular disease
• Current or prior history of hypertension or use of blood pressure lowering medications
• Current or prior history of diabetes mellitus or use of anti-diabetic medications
• Prevalent renal disease (eGFR < 60 ml/min/1.73m2), abnormal serum sodium or potassium
• Current or prior smoker
• Current pregnancy, or use of hormone replacement therapy or oral contraceptive
• Current steroid use
• Contraindications to MRI
• Active infection or open wounds on the top of the feet or hands

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low- then high-salt diet; 10 subjects will be enrolled and each will undergo study procedures at 4 separate visits. Subjects will be randomly assigned to this study arm, differing in the order of low and high salt diets. After a baseline visit to include a noninvasive MRI scan, the subject will begin this study diet: low-salt diet, then washout consisting of the subject's typical diet, then high-salt diet. Each dietary or washout period lasts for 7 days, and study visits will occur after each period.	Dietary supplement: Low-salt diet; The low-salt diet (7 days) will consist of meals, snacks and water provided by Vanderbilt's metabolic kitchen.; Dietary supplement: High-salt diet; The high-salt diet (7 days) consists of each subject's typical diet, supplemented each day with 2 bullion broth packets, which will be provided to the subject by the study staff.
Experimental: High- then low-salt diet; 10 subjects will be enrolled and each will undergo study procedures at 4 separate visits. Subjects will be randomly assigned to this study arm, differing in the order of low and high salt diets. After a baseline visit to include a noninvasive MRI scan, the subject will begin this study diet: high-salt diet, then washout consisting of the subject's typical diet, then low-salt diet. Each dietary or washout period lasts for 7 days, and study visits will occur after each period.	Dietary supplement: Low-salt diet; The low-salt diet (7 days) will consist of meals, snacks and water provided by Vanderbilt's metabolic kitchen.; Dietary supplement: High-salt diet; The high-salt diet (7 days) consists of each subject's typical diet, supplemented each day with 2 bullion broth packets, which will be provided to the subject by the study staff.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Salt-sensitive blood pressure after low salt diet	Measured as the difference in mean arterial pressure following high-salt diet compared to low-salt diet	Following completion of all dietary supplements and washout, in no less than 21 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue sodium content of the legs	Measured by sodium MRI	At baseline
Fat fraction of the legs	Measured by conventional MRI, in units of fat/water volume ratio	At baseline
Kidney blood perfusion rate	Measured by conventional noninvasive MRI	At baseline
Lymphatic stasis of the legs	Measured by noninvasive MR lymphangiography	At baseline
Urinary sodium excretion	Measured from 24-hour urine collection	At baseline and each of 3 study visits occurring about every 7 days, to be completed in no less than 21 days.
Plasma renin	Physiological parameter	At baseline and each of 3 study visits occurring about every 7 days, to be completed in no less than 21 days.
Serum aldosterone	Physiological parameter	At baseline and each of 3 study visits occurring about every 7 days, to be completed in no less than 21 days.

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Rachelle Crescenzi, PhD, Department of Radiology, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Crescenzi R, Marton A, Donahue PMC, Mahany HB, Lants SK, Wang P, Beckman JA, Donahue MJ, Titze J. Tissue Sodium Content is Elevated in the Skin and Subcutaneous Adipose Tissue in Women with Lipedema. Obesity (Silver Spring). 2018 Feb;26(2):310-317. doi: 10.1002/oby.22090. Epub 2017 Dec 27.
• Crescenzi R, Donahue PMC, Hartley KG, Desai AA, Scott AO, Braxton V, Mahany H, Lants SK, Donahue MJ. Lymphedema evaluation using noninvasive 3T MR lymphangiography. J Magn Reson Imaging. 2017 Nov;46(5):1349-1360. doi: 10.1002/jmri.25670. Epub 2017 Feb 28.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): November 4, 2022
• Study Completion (Actual): November 4, 2022

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 4, 2018

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: salt sensitive, blood pressure, obesity, magnetic resonance imaging
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 181610

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No