Visualizing Vascular Mechanisms of Salt Sensitivity

Sponsor:

Collaborators:

Information provided by (Responsible Party):

Rachelle Crescenzi，Vanderbilt University Medical Center

Tracking Information

First Submitted Date ^ICMJE

September 25, 2018

First Posted Date ^ICMJE

October 4, 2018

Last Update Posted Date

October 4, 2018

Actual Study Start Date ^ICMJE

November 1, 2018

Estimated Primary Completion Date

February 28, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Change in Salt-sensitive blood pressure after low salt diet[ Time Frame: Following completion of all dietary supplements and washout, in no less than 21 days. ]

Measured as the difference in mean arterial pressure following high-salt diet compared to low-salt diet

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

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

Descriptive Information

Brief Title ^ICMJE

Visualizing Vascular Mechanisms of Salt Sensitivity

Official Title ^ICMJE

Visualizing Vascular Mechanisms of Salt Sensitivity

Brief Summary

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

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 ^ICMJE

Interventional

Study Phase

N/A

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Basic Science

Condition ^ICMJE

Intervention ^ICMJE

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.

Study Arms

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.
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.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

June 30, 2021

Estimated Primary Completion Date

February 28, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Yes

Responsible Party

Rachelle Crescenzi，Vanderbilt University Medical Center

Study Sponsor ^ICMJE

Vanderbilt University Medical Center

Collaborators ^ICMJE

Investigators ^ICMJE

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

PRS Account

Vanderbilt University Medical Center

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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