Clinical trial NCT00896389: Salt Loading and Thiazide Intervention Study
Official title: The Relationship Between Serine Threonine Kinase 39 (STK39) Genotypes, Salt Sensitivity, Thiazide Diuretics-induced Blood Pressure Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: hypertension
hydrochlorothiazide
HCTZ
Salt sensitivity
Hydrochlorothiazide induced hyperglycemia
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2009-05-11
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Blood Pressure Change During Salt Loading
timeFrame: Every 15 minutes for 4 hours
measure: Blood Pressure Change After 7 Days of Low Dose (12.5 mg) of HCTZ
timeFrame: 24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8
measure: Blood Pressure Change After 7 Days of High Dose (25 mg) of HCTZ
timeFrame: 24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8
measure: Fasting Glucose Change After 7 Days of Low Dose (12.5 mg) of HCTZ
timeFrame: Fasting glucose was measured on day 0 and day 8
measure: Fasting Glucose Change After 7 Days of High Dose (25mg) of HCTZ
timeFrame: Fasting glucose was measured on day 0 and day 8
Secondary outcomes:
measure: Change in Plasma Aldosterone Level Due to Salt-loading
timeFrame: Aldosterone was measured from blood collected pre and post salt loading
measure: Change in Plasma Renin Activity Due to Salt-loading
timeFrame: Renin was measured from blood collected pre and post salt loading
measure: Change in Plasma Sodium/Potassium Level Due to Salt-loading
timeFrame: Plasma sodium and potassium measured from blood collected pre and post salt loading
measure: Change in Plasma Sodium/Potassium Level During Low Dose of HCTZ
timeFrame: Plasma sodium and potassium measured from blood collected pre and post salt loading
measure: Change in Plasma Sodium/Potassium Level During High Dose of HCTZ
timeFrame: Plasma sodium and potassium measured from blood collected pre and post salt loading
Other outcomes:
Locations:
city: Lancaster
country: United States
facility: Amish Research Clinics
state: Pennsylvania
Study officials:
affiliation: University of Maryland, Baltimore
name: Yen Pei C. Chang, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang Y, O'Connell JR, McArdle PF, Wade JB, Dorff SE, Shah SJ, Shi X, Pan L, Rampersaud E, Shen H, Kim JD, Subramanya AR, Steinle NI, Parsa A, Ober CC, Welling PA, Chakravarti A, Weder AB, Cooper RS, Mitchell BD, Shuldiner AR, Chang YP. From the Cover: Whole-genome association study identifies STK39 as a hypertension susceptibility gene. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):226-31. doi: 10.1073/pnas.0808358106. Epub 2008 Dec 29.
citation: Delpire E, Gagnon KB. SPAK and OSR1: STE20 kinases involved in the regulation of ion homoeostasis and volume control in mammalian cells. Biochem J. 2008 Jan 15;409(2):321-31. doi: 10.1042/BJ20071324.
citation: Chiga M, Rai T, Yang SS, Ohta A, Takizawa T, Sasaki S, Uchida S. Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone. Kidney Int. 2008 Dec;74(11):1403-9. doi: 10.1038/ki.2008.451. Epub 2008 Sep 17.