Clinical trial NCT01899495: Blood Pressure Response to Sodium in the Diet
Official title: D1 and AT1 Receptor Interaction in Human Hypertension: Sodium Sensitivity of Blood Pressure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypertension
Keywords: blood pressure
hypertension
salt sensitivity
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-07-15
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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 .

Eligibility 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

Primary outcomes:
measure: Blood pressure; Change in Mean Arterial Pressure from low salt diet to high salt diet
timeFrame: Study subjects will be observed 5 times during the 2 week intervention
Secondary outcomes:
measure: Urine sodium
timeFrame: Urine chemistry analysis will be assessed from a 24-hour urine collection on the last day of each diet week.
measure: Genetic analysis for specified genes associated with hypertension
timeFrame: During the screening visit
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia
name: Robert M Carey, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: http://hyper.ahajournals.org/content/early/2012/09/17/HYPERTENSIONAHA.112.196071.full.pdf