Salt Loading and Thiazide Intervention Study

University of Maryland, Baltimore124 enrolled

Overview

The investigators of this study propose to examine the relationships between STK39 (Serine Threonine Kinase 39) genotypes and responses to salt loading and to thiazide diuretics, hydrochlorothiazide. The investigators hypothesize that STK39 genotypes will be associated with the outcome of both interventions and can contribute to personalized care for hypertension.

Although hypertension can be easily diagnosed and there are many medications available to treat hypertension, this condition is poorly managed in many patients and is a leading cause of morbidity and mortality worldwide. Because a newly identified hypertension susceptibility gene, STK39 (Serine Threonine Kinase 39), plays a central role in kidney sodium transport, the investigators propose a pharmacogenetics study to examine the relationships between STK39 genotypes and blood pressure responses to salt loading and to thiazide diuretics, hydrochlorothiazide. In addition, STK39 genotypes may also predict those hypertension patients more likely to develop thiazide-induced hyperglycemia. The investigators hypothesize that STK39 genotypes of those single nucleotide polymorphisms (SNPs) that are associated with baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension status, will be associated with the outcome of both interventions. Therefore these SNPs can act as markers and contribute to personalized care for hypertension by identifying patients most likely to effectively control their blood pressure by adopting salt-reducing diet versus patients most likely to effectively and safely control their blood pressure by taking thiazide diuretics.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

124

Conditions

Hypertension

Interventions

Salt loadingPROCEDURE

Subjects will arrive at the Amish Research Clinics after overnight fasting. After taking height, weight, BP, and body temperature, subjects will receive 2 liters (L) of 0.9% sodium chloride (NaCl) saline over 4 hours while their blood pressure is monitored every 15 minutes. Blood pressure will be taken every 15 minutes during this procedure. Blood and urine samples will be collected from all subjects pre- and post-infusion.

Hydrochlorothiazide (HCTZ)DRUG

We will perform short-term HCTZ intervention on the same 120 subjects. After overnight fasting and having their height, weight, and BP measured, subjects are given seven 12.5 mg HCTZ tablets and instructed to take 1 tablet daily for one week. Ambulatory blood pressure will be measured and blood and urine will be collected on both day 1 and day 8. After a minimum 6-week wash-out period, the subjects will repeat the 7-day HCTZ intervention, taking 25 mg of HCTZ instead. Subjects with plasma potassium levels below 3.6 mmol/L on day 8 of 12.5 mg HCTZ will be given a daily supplement of 16 milliequivalents of potassium to prevent harmful loss of potassium while taking HCTZ.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Old Order Amish * Age 18 to 65 * Have systolic blood pressure between 120 and 160 and diastolic blood pressure between 80 and 100 Exclusion Criteria: * History of myocardial infarction, stroke, congestive heart failure, liver disease * Known cause of secondary hypertension * Diabetes or Fasting glucose \> 100 mg/dL * Women who are pregnant, on oral contraceptives, or menstruating * Used hydrochlorothiazide (HCTZ) in the last 8 weeks or known allergy to HCTZ * Taking non-steroidal anti-inflammatory drugs * Estimated glomerular filtration rate \< 80 mL/m * Intention to alter dietary habit during the study * Abuse of alcohol or drug

Locations (1)

Amish Research Clinics

Lancaster, Pennsylvania, United States

Outcomes

Primary Outcomes

Blood Pressure Change During Salt Loading

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured every 15 minutes for 4 hours. Blood pressure change is calculated by the trapezoid method. Essentially we use the average of blood pressure at each pair of time points (for example, DBP 30min + DBP 15min)/2 + (DBP 45min + DBP 30min)/2 + … up to 4 hours.) normalized by baseline SBP/DBP.

Time frame: Every 15 minutes for 4 hours

Blood Pressure Change After 7 Days of Low Dose (12.5 mg) of HCTZ

Blood pressure change is defined as SBP or DBP average over the 24 hour period, Day 8 subtracts Day 0.

Time frame: 24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8

Blood Pressure Change After 7 Days of High Dose (25 mg) of HCTZ

Blood pressure change is defined as SBP or DBP average over the 24 hour period, Day 8 subtracts Day 0.

Time frame: 24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8

Fasting Glucose Change After 7 Days of Low Dose (12.5 mg) of HCTZ

Values on Day 8 subtracts Day 0.

Time frame: Fasting glucose was measured on day 0 and day 8

Fasting Glucose Change After 7 Days of High Dose (25mg) of HCTZ

Values on Day 8 subtracts Day 0.

Time frame: Fasting glucose was measured on day 0 and day 8

Secondary Outcomes

Change in Plasma Aldosterone Level Due to Salt-loading

Aldosterone is a hormone that plays a critical role in homeostatic regulation of blood pressure. Change is defined as the post-salt loading values minus the pre-salt loading values

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.