Blood Pressure Response to Sodium in the Diet

• ClinicalTrials.gov Identifier: NCT01899495
• Recruitment Status: Recruiting
• First Posted: July 15, 2013
• Last Update Posted: October 18, 2016
• Sponsor: University of Virginia
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Robert M. Carey, MD, University of Virginia

Study Description

Brief Summary:

Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low sodium (Na+) and 7 days of high Na+ intake. Salt sensitivity was defined as a ≥7-mm Hg increase in mean arterial pressure during a randomized transition between low and high Na+ diet.

A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity. Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0×10-4 and 3.1×10-4 with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9×10-5 and 2.6×10-4 and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2×10-5]; rs1017783 [P=1.1×10-4]).

In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.

Condition or disease	Intervention/treatment	Phase
Hypertension	Other: High sodium diet and low sodium diet	Not Applicable

Detailed Description:

Subjects are placed on an isocaloric diet, one week with high sodium(300mEq) and one week with low sodium(10mEq), in randomized order. Twenty-four hour urine sodium and urine creatinine levels verify diet compliance. Blood pressure measurements are recorded during each diet week by automated blood pressure monitoring system. Each blood pressure is taken in the right arm 3 times while the subject is sitting quietly for 45 minutes .

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: D1 and AT1 Receptor Interaction in Human Hypertension: Sodium Sensitivity of Blood Pressure
• Study Start Date: January 2005
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: August 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: High sodium diet and low sodium diet; Each subject experiences both a high sodium and a low sodium diet.	Other: High sodium diet and low sodium diet; Isocaloric diet with 60 mEq of potassium and 1gm protein/kg body weight with high sodium 300mEq; low sodium 10 mEq.

Outcome Measures

Primary Outcome Measures :

1. Blood pressure; Change in Mean Arterial Pressure from low salt diet to high salt diet [ Time Frame: Study subjects will be observed 5 times during the 2 week intervention ]
   The mean arterial pressure that will determine salt sensitivity will be assessed during the last day of the diet week. The study will be stopped for any individual during any visit if there is an average blood pressure of >180/114 mmHg.

Secondary Outcome Measures :

1. Urine sodium [ Time Frame: Urine chemistry analysis will be assessed from a 24-hour urine collection on the last day of each diet week. ]
2. Genetic analysis for specified genes associated with hypertension [ Time Frame: During the screening visit ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Ages 18-70 (inclusive)
• Sex Male and female
• Race Caucasian and African-American/black
• BMI 18.-0-29.9
• BP Normal

Exclusion Criteria:

• hypertension
• blood pressure > 140/90 mmHg

Contacts and Locations

Locations

United States, Virginia

University of Virginia; Recruiting

Charlottesville, Virginia, United States, 22903

Contact: Mahabuba Akhter, M.B.B.S, MS 434-924-8757 SaltSensitivityStudy@email.virginia.edu

Principal Investigator: Robert M Carey, MD

Sponsors and Collaborators

University of Virginia

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Robert M Carey, MD; University of Virginia

More Information

Publications of Results:

http://hyper.ahajournals.org/content/early/2012/09/17/HYPERTENSIONAHA.112.196071.full.pdf

• Responsible Party: Robert M. Carey, MD, Professor of Medicine; Dean, Emeritus; University Professor Division of Endocrinology and Metabolism, University of Virginia
• ClinicalTrials.gov Identifier: NCT01899495
• Other Study ID Numbers: 11494; P01HL074940 ( U.S. NIH Grant/Contract )
• First Posted: July 15, 2013
• Last Update Posted: October 18, 2016
• Last Verified: October 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Robert M. Carey, MD, University of Virginia:

blood pressure; hypertension; salt sensitivity

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases