The Effect of Thiazide, Amiloride and Hypertonic Saline on Urinary Biomarkers in Healthy Subjects (THAM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Erling Bjerregaard Pedersen, Regional Hospital Holstebro
ClinicalTrials.gov Identifier:
NCT01635231
First received: June 13, 2012
Last updated: March 1, 2014
Last verified: March 2014
  Purpose

Urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2) reflects the activity of the sodium- and water channels in the human kidney.

Changes in the sodium-and water channel activity can be induced by blocking the sodium channels with diuretics in healthy subjects


Condition Intervention
Nephropathy
Other: hypertonic saline

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Diagnostic
Official Title: Effect of Thiazide, Amiloride and Hypertonic Saline on Sodium- and Water Channel Activity in the Nephron in Healthy Subjects Estimated by Urinary Biomarkers

Resource links provided by NLM:


Further study details as provided by Regional Hospital Holstebro:

Primary Outcome Measures:
  • urinary biomarkers [ Time Frame: baseline, 0 hours and 1.5 hours after intervention ] [ Designated as safety issue: No ]
    Urinary excretion of epithelial sodium channels (ENaC), Sodium-potassium-2chloride transporters (NKCC2) and aquaporin2 channels (AQP2) before, during and after fluid infusion


Secondary Outcome Measures:
  • vaso active hormones [ Time Frame: baseline, 0 hours and 1.5 hours after intervention ] [ Designated as safety issue: No ]
    plasma concentrations of: renin, Angiotensin II, aldosterone, Vasopressin, ANP and BNP

  • central blood pressure [ Time Frame: baseline, 0 hours and 1.5 hours after intervention ] [ Designated as safety issue: No ]
    measured by applanation-tonometry

  • intracellular (ICV)- and extracellular volume (ECV) [ Time Frame: baseline, 0 hours and 1.5 hours after intervention ] [ Designated as safety issue: No ]
    change in ICV and EVC from baseline and after intervention measured in liters by body composition monitor (BCM)


Enrollment: 24
Study Start Date: July 2012
Study Completion Date: November 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: thiazide, diuretic
1.25 mg thiazide twice daily for 5 days
Other: hypertonic saline
hypertonic saline 3.0% 7 ml/kg
Other Name: NaCl 3.0 %
Active Comparator: amiloride, diuretic
5 mg of amiloride twice daily
Other: hypertonic saline
hypertonic saline 3.0% 7 ml/kg
Other Name: NaCl 3.0 %
Placebo Comparator: calcium
placebo twice daily for 5 days
Other: hypertonic saline
hypertonic saline 3.0% 7 ml/kg
Other Name: NaCl 3.0 %

Detailed Description:
  1. Urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2) reflects the kidneys transport of sodium and water in the nephron.
  2. Changes in the sodium-and water channel activity is induced by blocking the NCC channels with thiazide and ENaC channels with amiloride and by intervention with hypertonic NaCl The changes in sodium-and water channels are followed by changes in extracellular and intracellular fluids, central bloodpressure and the plasma concentration of vasoactive hormones.

The purpose of this study is to investigate the changes in urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2), extra- and intracellular fluid compartments, central bloodpressure and the plasma concentration of Vasoactive hormones in healthy subjects under a) treatment with Amiloride and Thiazide at baseline and b) after and acute infusion with hypertonic saline.

Subjects will be examined on three examination days. Four days prior to the examination days the subjects will consume a standard diet based on amount of sodium and calories and randomized to treatment with either thiazide, amiloride or placebo twice daily for 5 days. On the examination days the subjects receive an infusion with hypertonic saline.

Renal function is measured by renal clearance of 51Cr-EDTA. Urinary biomarkers (u-NKCC2, u-ENaC-gamma and u-AQP2) will be measured to evaluate the activity of water- and sodium channels in the nephron, changes in fluid compartments are measured by body composition monitor. Central blood pressure is measured by sphygmocor.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy males and females
  • age 18-45
  • BMI range 18,5-30,0 kg/m2

Exclusion Criteria:

  • hypertension (i.e. ambulatory BP > 130 mmHg systolic or/and > 80 mmHg diastolic)
  • history or clinical significant signs of heart, lung, liver, kidney, endocrine, brain or neoplastic
  • disease.
  • alcohol abuse
  • drug abuse
  • smoking
  • pregnancy or nursing
  • blood donation within a month prior to examination
  • medical treatment apart from oral contraception abnormal blood samples, -ECG and -urine dipstick, drug abuse, alcohol abuse, pregnancy, medication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01635231

Locations
Denmark
Medical Research
Holstebro, Denmark, 7500
Sponsors and Collaborators
Regional Hospital Holstebro
Investigators
Study Director: Erling B Pedersen, MD, DMSc Medical Research, Holstebro
  More Information

No publications provided

Responsible Party: Erling Bjerregaard Pedersen, Ph.d student Janni Majgaard Jensen, Regional Hospital Holstebro
ClinicalTrials.gov Identifier: NCT01635231     History of Changes
Other Study ID Numbers: EBP-JMJ-2012-1
Study First Received: June 13, 2012
Last Updated: March 1, 2014
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Ethics Committee

Keywords provided by Regional Hospital Holstebro:
Nephrology
sodium-channels
water-channels
BCM
central blood pressure

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Amiloride
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Acid Sensing Ion Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Epithelial Sodium Channel Blockers
Diuretics, Potassium Sparing
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 25, 2014