Salt Loading and Thiazide Intervention Study - Full Text View

Sponsor:	University of Maryland
Collaborator:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	University of Maryland
ClinicalTrials.gov Identifier:	NCT00896389

Purpose

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, 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.

Condition	Intervention	Phase
Hypertension	Procedure: Salt loading Drug: Hydrochlorothiazide (HCTZ)	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	The Relationship Between STK39 Genotypes, Salt Sensitivity, Thiazide Diuretics-induced Blood Pressure Response

Resource links provided by NLM:

MedlinePlus related topics: Dietary Sodium High Blood Pressure

Drug Information available for: Hydrochlorothiazide Sodium chloride

U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:

Blood pressure changes [ Time Frame: Two hours for the salt loading intervention and 7 days for the hydrochlorothiazide intervention ] [ Designated as safety issue: No ]
Fasting glucose level [ Time Frame: 7 days for the hydrochlorothiazide intervention ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Plasma HCTZ concentration [ Time Frame: 7 days for the hydrochlorothiazide intervention ] [ Designated as safety issue: No ]
Serum potassium level [ Time Frame: 7 days for the hydrochlorothiazide intervention ] [ Designated as safety issue: Yes ]
Other changes in blood chemistry, such as in serum Na, Cl, and blood urea nitrogen [ Time Frame: Two hours for the salt loading intervention and 7 days for the hydrochlorothiazide intervention ] [ Designated as safety issue: No ]
Changes in urine chemistry, such as pH, protein, creatinine [ Time Frame: Two hours for the salt loading intervention and 7 days for the hydrochlorothiazide intervention ] [ Designated as safety issue: No ]

Estimated Enrollment:	120
Study Start Date:	October 2009
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
All: Experimental All subject will undergo salt loading and hydrochlorothiazide interventions. Pre-and post interventions phenotypes will be analyzed.	Procedure: Salt loading We will perform salt loading intervention, a routinely prescribed diagnostic test to determine if patients have hypoaldosteronism, on 120 subjects. After overnight fasting, subjects will arrive at the Amish Research clinics. After taking height, weight, BP, and body temperature (intervention will not proceed if fever is detected), the patient will be in supine position, have IV line inserted and fitted for an automatic BP monitor. BP will be taken every 5 minutes until the last 3 SBP readings are within 3 mmHg. Once the BP has "equilibrated" 2 L of 0.9% NaCl saline will be intravenously infused over 2 hours. BP will be taken every 15 minutes during this procedure and for 2 hours after the intervention. Blood and urine samples will be collected from all subjects pre- and post-infusion. Drug: Hydrochlorothiazide (HCTZ) We will perform short-term HCTZ intervention on the same 120 subjects.The subjects will arrive to the ARC after overnight fasting (day 1), have 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. The subjects will return to ARC on day 8 and have height, weight, and BP measured again. Blood and urine will be collected on both day 1 and day 8. After a minimum 6-week wash-out period, the subjects will come back to the ARC and repeat the 7-day diuretics 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.

Arms

Assigned Interventions

All: Experimental

All subject will undergo salt loading and hydrochlorothiazide interventions. Pre-and post interventions phenotypes will be analyzed.

Procedure: Salt loading

We will perform salt loading intervention, a routinely prescribed diagnostic test to determine if patients have hypoaldosteronism, on 120 subjects. After overnight fasting, subjects will arrive at the Amish Research clinics. After taking height, weight, BP, and body temperature (intervention will not proceed if fever is detected), the patient will be in supine position, have IV line inserted and fitted for an automatic BP monitor. BP will be taken every 5 minutes until the last 3 SBP readings are within 3 mmHg. Once the BP has "equilibrated" 2 L of 0.9% NaCl saline will be intravenously infused over 2 hours. BP will be taken every 15 minutes during this procedure and for 2 hours after the intervention. Blood and urine samples will be collected from all subjects pre- and post-infusion.

Drug: Hydrochlorothiazide (HCTZ)

We will perform short-term HCTZ intervention on the same 120 subjects.The subjects will arrive to the ARC after overnight fasting (day 1), have 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. The subjects will return to ARC on day 8 and have height, weight, and BP measured again. Blood and urine will be collected on both day 1 and day 8. After a minimum 6-week wash-out period, the subjects will come back to the ARC and repeat the 7-day diuretics 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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Old Order Amish
Age 18 to 65
Have systolic blood pressure between 130 and 160 and diastolic blood pressure between 85 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00896389

Contacts

Contact: Mary Morrissey, R.N.

717-392-4948

mmorrissey@medicine.umaryland.edu

Locations

United States, Pennsylvania
Amish Research Clinics	Recruiting
Lancaster, Pennsylvania, United States, 17607
Contact: Mary Morrissey, R.N. 717-392-4948 mmorrissey@medicine.umaryland.edu
Sub-Investigator: Arohan Subramanya, M.D.
Principal Investigator: Yen Pei C. Chang, Ph.D.
Sub-Investigator: Alan Shuldiner, M.D.

Sponsors and Collaborators

University of Maryland

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator:

Yen Pei C. Chang, Ph.D.

University of Maryland

More Information

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. 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. Epub 2008 Sep 17.

Responsible Party:	University of Maryland ( Yen-Pei Christy Chang )
Study ID Numbers:	HP-00040712, 1R21DK084566-01
Study First Received:	May 7, 2009
Last Updated:	November 5, 2009
ClinicalTrials.gov Identifier:	NCT00896389 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Maryland:

hypertension
hydrochlorothiazide
HCTZ

salt sensitivity
Salt sensitivity
Hydrochlorothiazide induced hyperglycemia

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Diuretics
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Vascular Diseases
Cardiovascular Agents
Antihypertensive Agents

Hydrochlorothiazide
Pharmacologic Actions
Membrane Transport Modulators
Natriuretic Agents
Therapeutic Uses
Cardiovascular Diseases
Hypertension

ClinicalTrials.gov processed this record on February 08, 2010