Salt Loading and Thiazide Intervention Study

NCT00896389 | Completed Phase 4 Results DMC

• 2 other identifiers: HP-00040712R21DK084566
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

hypertension; hydrochlorothiazide; HCTZ; Salt sensitivity; Hydrochlorothiazide induced hyperglycemia

Outcome Measures

Primary Outcomes (5)

• Blood Pressure Change During Salt Loading

  Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured every 15 minutes for 4 hours. Blood pressure change is calculated by the trapezoid method. Essentially we use the average of blood pressure at each pair of time points (for example, DBP 30min + DBP 15min)/2 + (DBP 45min + DBP 30min)/2 + … up to 4 hours.) normalized by baseline SBP/DBP.

  Every 15 minutes for 4 hours

• Blood Pressure Change After 7 Days of Low Dose (12.5 mg) of HCTZ

  Blood pressure change is defined as SBP or DBP average over the 24 hour period, Day 8 subtracts Day 0.

  24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8

• Blood Pressure Change After 7 Days of High Dose (25 mg) of HCTZ

  Blood pressure change is defined as SBP or DBP average over the 24 hour period, Day 8 subtracts Day 0.

  24-hr Ambulatory blood pressure were measured every hour on day 0 and day 8

• Fasting Glucose Change After 7 Days of Low Dose (12.5 mg) of HCTZ

  Values on Day 8 subtracts Day 0.

  Fasting glucose was measured on day 0 and day 8

• Fasting Glucose Change After 7 Days of High Dose (25mg) of HCTZ

  Values on Day 8 subtracts Day 0.

  Fasting glucose was measured on day 0 and day 8

Secondary Outcomes (5)

• Change in Plasma Aldosterone Level Due to Salt-loading

  Aldosterone was measured from blood collected pre and post salt loading

• Change in Plasma Renin Activity Due to Salt-loading

  Renin was measured from blood collected pre and post salt loading

• Change in Plasma Sodium/Potassium Level Due to Salt-loading

  Plasma sodium and potassium measured from blood collected pre and post salt loading

• Change in Plasma Sodium/Potassium Level During Low Dose of HCTZ

  Plasma sodium and potassium measured from blood collected pre and post salt loading

• Change in Plasma Sodium/Potassium Level During High Dose of HCTZ

  Plasma sodium and potassium measured from blood collected pre and post salt loading

Study Arms (1)

Salt-loading and thiazide diuretic (HCTZ)

OTHER

Salt loading:2 L of 0.9% NaCl. HCTZ:12.5/ 25 mg of HCTZ for 1 week

Procedure: Salt loading; Drug: Hydrochlorothiazide (HCTZ)

Interventions

Salt loading PROCEDURE

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.

Salt-loading and thiazide diuretic (HCTZ)

Hydrochlorothiazide (HCTZ) DRUG

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.

Also known as: Hydrochlorothiazide, HCTZ, Apo-Hydro, Aquazide H, Dichlotride, Hydrodiuril, HydroSaluric, Microzide, Esidrex, Oretic.

Salt-loading and thiazide diuretic (HCTZ)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Old Order Amish
• Age 18 to 65
• Have systolic blood pressure between 120 and 160 and diastolic blood pressure between 80 and 100

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Amish Research Clinics

Lancaster, Pennsylvania, 17607, United States

Location

Related Publications (3)

• 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.

  PMID: 19114657 BACKGROUND

• 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.

  PMID: 18092945 BACKGROUND

• 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.

  PMID: 18800028 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Yen Pei Christy Chang
• Organization: University of Maryland, Baltimore

cchang@som.umaryland.edu

410-706-6737

Study Officials

• Yen Pei C. Chang, Ph.D.

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 7, 2009
• First Posted: May 11, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: March 1, 2013
• Last Updated: March 25, 2022
• Results First Posted: May 31, 2018

Record last verified: 2022-03

Locations

US (1)