Salt Loading and Thiazide Intervention Study

Phase 4

Completed

Conditions: Hypertension

Interventions: Procedure: Salt loading
Drug: Hydrochlorothiazide (HCTZ)

Registration Number: NCT00896389

Lead Sponsor: University of Maryland, Baltimore

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 124

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Salt-loading and thiazide diuretic (HCTZ)	Hydrochlorothiazide (HCTZ)	Salt loading:2 L of 0.9% NaCl. HCTZ:12.5/ 25 mg of HCTZ for 1 week
Salt-loading and thiazide diuretic (HCTZ)	Salt loading	Salt loading:2 L of 0.9% NaCl. HCTZ:12.5/ 25 mg of HCTZ for 1 week

Primary Outcome Measures

Name	Time	Method
Fasting Glucose Change After 7 Days of High Dose (25mg) of HCTZ	Fasting glucose was measured on day 0 and day 8	Values on Day 8 subtracts Day 0.
Blood Pressure Change After 7 Days of Low Dose (12.5 mg) of HCTZ	24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8	Blood pressure change is defined as SBP or DBP average over the 24 hour period, Day 8 subtracts Day 0.
Blood Pressure Change After 7 Days of High Dose (25 mg) of HCTZ	24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8	Blood pressure change is defined as SBP or DBP average over the 24 hour period, Day 8 subtracts Day 0.
Fasting Glucose Change After 7 Days of Low Dose (12.5 mg) of HCTZ	Fasting glucose was measured on day 0 and day 8	Values on Day 8 subtracts Day 0.
Blood Pressure Change During Salt Loading	Every 15 minutes for 4 hours	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.

Secondary Outcome Measures

Name	Time	Method
Change in Plasma Sodium/Potassium Level Due to Salt-loading	Plasma sodium and potassium measured from blood collected pre and post salt loading	Na/K ratio is a function of kidney function
Change in Plasma Sodium/Potassium Level During Low Dose of HCTZ	Plasma sodium and potassium measured from blood collected pre and post salt loading	Na/K ratio is a function of kidney function
Change in Plasma Aldosterone Level Due to Salt-loading	Aldosterone was measured from blood collected pre and post 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
Change in Plasma Renin Activity Due to Salt-loading	Renin was measured from blood collected pre and post salt loading	Renin is an enzyme that mediates extracellular fluid and regulates blood pressure. Plasma renin activity (PRA) is a measure of the activity of the plasma enzyme renin. PRA is measured in the laboratory by incubating plasma at physiologic temperature in a buffer that facilitates its enzymatic activity. The natural substrate for the enzyme renin is angiotensinogen. Exogenous angiotensinogen is not added to the reaction mixture. This means that, in effect, the PRA results reported are dependent on both renin concentration and the concentration of its substrate in the patient's plasma. Renin cleaves angiotensinogen to produce a decapeptide, angiotensin I, the concentration of which is assayed using liquid chromatography accompanied by tandem mass spectroscopic detection (LC/MS/MS). PRA levels are reported as the amount of angiotensin I generated per unit of time. Change is defined as the post-salt loading values minus the pre-salt loading values
Change in Plasma Sodium/Potassium Level During High Dose of HCTZ	Plasma sodium and potassium measured from blood collected pre and post salt loading	Na/K ratio is a function of kidney function