Clincosm LogoSign in Get a demo

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

Sponsor
Regional Hospital Holstebro (Other)
Overall Status
Completed
CT.gov ID
NCT01635231
Collaborator
(none)
24
Enrollment
1
Location
3
Arms
16
Duration (Months)
1.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • Other: hypertonic saline
 N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Triple (Participant, Care Provider, 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
Study Start Date :
Jul 1, 2012
Actual Primary Completion Date :
Sep 1, 2013
Actual Study Completion Date :
Nov 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: thiazide, diuretic

1.25 mg thiazide twice daily for 5 days

Other: hypertonic saline
hypertonic saline 3.0% 7 ml/kg
Other Names:
  • NaCl 3.0 %

    		•
    Active Comparator: amiloride, diuretic

    5 mg of amiloride twice daily

    Other: hypertonic saline
    hypertonic saline 3.0% 7 ml/kg
    Other Names:
  • NaCl 3.0 %

    		•
    Placebo Comparator: calcium

    placebo twice daily for 5 days

    Other: hypertonic saline
    hypertonic saline 3.0% 7 ml/kg
    Other Names:
  • NaCl 3.0 %

    		•

    Outcome Measures

    Primary Outcome Measures

    1. urinary biomarkers [baseline, 0 hours and 1.5 hours after intervention]

      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

    1. vaso active hormones [baseline, 0 hours and 1.5 hours after intervention]

      plasma concentrations of: renin, Angiotensin II, aldosterone, Vasopressin, ANP and BNP

    2. central blood pressure [baseline, 0 hours and 1.5 hours after intervention]

      measured by applanation-tonometry

    3. intracellular (ICV)- and extracellular volume (ECV) [baseline, 0 hours and 1.5 hours after intervention]

      change in ICV and EVC from baseline and after intervention measured in liters by body composition monitor (BCM)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Locations

    Site City State Country Postal Code
    1 Medical Research Holstebro Denmark 7500

    Sponsors and Collaborators

    • Regional Hospital Holstebro

    Investigators

    • Study Director: Erling B Pedersen, MD, DMSc, Medical Research, Holstebro

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Erling Bjerregaard Pedersen, Ph.d student Janni Majgaard Jensen, Regional Hospital Holstebro
    ClinicalTrials.gov Identifier:
    NCT01635231
    Other Study ID Numbers:
    • EBP-JMJ-2012-1
    First Posted:
    Jul 9, 2012
    Last Update Posted:
    Mar 4, 2014
    Last Verified:
    Mar 1, 2014
    Keywords provided by Erling Bjerregaard Pedersen, Ph.d student Janni Majgaard Jensen, Regional Hospital Holstebro
    Nephrology
    sodium-channels
    water-channels
    BCM
    central blood pressure
    Additional relevant MeSH terms:
    Kidney Diseases

    Study Results

    No Results Posted as of Mar 4, 2014