Salt Loading and Thiazide Intervention Study

Condition(s) targeted: Hypertension

Intervention: Salt loading (Procedure); Hydrochlorothiazide (HCTZ) (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Maryland

Official(s) and/or principal investigator(s):
Yen Pei C. Chang, Ph.D., Principal Investigator, Affiliation: University of Maryland, Baltimore County

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 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 by predicting patients most likely to effectively control their blood pressure by adopting salt-reducing diet and taking thiazide diuretics.

Official title: The Relationship Between STK39 Genotypes, Salt Sensitivity, Thiazide Diuretics-induced Blood Pressure Response

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Blood pressure changes

Fasting glucose level

Secondary outcome:

Plasma HCTZ concentration

Serum potassium level

Other changes in blood chemistry, such as in serum Na, Cl, and blood urea nitrogen

Changes in urine chemistry, such as pH, protein, creatinine

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

Amish Research Clinics, Lancaster, Pennsylvania 17607, United States

Related publications:

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.

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. Review.

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.

Starting date: October 2009
Last updated: June 24, 2013