Salt Loading and Thiazide Intervention Study (SALTI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00896389
Recruitment Status : Completed
First Posted : May 11, 2009
Last Update Posted : June 26, 2013
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Yen Pei C. Chang, Ph.D, University of Maryland

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hypertension Procedure: Salt loading Drug: Hydrochlorothiazide (HCTZ) Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 124 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Relationship Between STK39 Genotypes, Salt Sensitivity, Thiazide Diuretics-induced Blood Pressure Response
Study Start Date : October 2009
Actual Primary Completion Date : December 2012
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sodium
U.S. FDA Resources

Arm Intervention/treatment
Experimental: All
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 (systolic blood pressure) readings are within 3 mmHg. Once the BP has "equilibrated" 2 L of 0.9% NaCl (sodium chloride) saline will be intravenously infused over 4 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.
Other Names:
  • Hydrochlorothiazide
  • HCTZ
  • Apo-Hydro
  • Aquazide H
  • Dichlotride
  • Hydrodiuril
  • HydroSaluric
  • Microzide
  • Esidrex
  • Oretic.

Primary Outcome Measures :
  1. Blood pressure changes [ Time Frame: Four hours for the salt loading intervention and 7 days for the hydrochlorothiazide intervention ]
  2. Fasting glucose level [ Time Frame: 7 days for the hydrochlorothiazide intervention ]

Secondary Outcome Measures :
  1. Plasma HCTZ concentration [ Time Frame: 7 days for the hydrochlorothiazide intervention ]
  2. Serum potassium level [ Time Frame: 7 days for the hydrochlorothiazide intervention ]
  3. Other changes in blood chemistry, such as in serum Na, Cl, and blood urea nitrogen [ Time Frame: Four hours for the salt loading intervention and 7 days for the hydrochlorothiazide intervention ]
  4. 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 ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00896389

United States, Pennsylvania
Amish Research Clinics
Lancaster, Pennsylvania, United States, 17607
Sponsors and Collaborators
University of Maryland
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Yen Pei C. Chang, Ph.D. University of Maryland

Responsible Party: Yen Pei C. Chang, Ph.D, Associate professor, University of Maryland Identifier: NCT00896389     History of Changes
Other Study ID Numbers: HP-00040712
R21DK084566 ( U.S. NIH Grant/Contract )
First Posted: May 11, 2009    Key Record Dates
Last Update Posted: June 26, 2013
Last Verified: June 2013

Keywords provided by Yen Pei C. Chang, Ph.D, University of Maryland:
salt sensitivity
Hydrochlorothiazide induced hyperglycemia

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action