Salt Loading and Thiazide Intervention Study
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Salt loading; Hydrochlorothiazide (HCTZ)
Intervention type(s): Procedure; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Hydrochlorothiazide; HCTZ; Apo-Hydro; Aquazide H; Dichlotride; Hydrodiuril; HydroSaluric; Microzide; Esidrex; Oretic.
Intervention MeSH terms: Hydrochlorothiazide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hypertension; hydrochlorothiazide; HCTZ; Salt sensitivity; Hydrochlorothiazide induced hyperglycemia