Effect of the Aquaretic Tolvaptan on Nitric Oxide System (TORA)

October 8, 2014 updated by: Erling Bjerregaard Pedersen, Regional Hospital Holstebro

Effect of Vasopressin Antagonism on Renal Sodium and Water Handling and Circulation During Inhibition of the Nitric Oxide System in Healthy Subjects

The purpose of this study is to investigate the effect of tolvaptan on renal water, sodium and potassium excretion, plasma concentration of vasoactive hormones,central blood pressure, pulse wave velocity (PWV) and augmentation index, basal and during inhibition of nitric oxide synthesis in healthy subjects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Tolvaptan is a vasopressin antagonist (V2-antagonist) and is used in treatment of hyponatremia. Animal studies have demonstrated that inhibition of V2 receptors in the renal principal cell increases renal free water clearance and renal sodium excretion.

Treatment with V2-receptor antagonists increases vasopressin concentration in plasma that stimulates V1-receptors in the vascular bed. This may change both central and peripheral hemodynamics and plasma concentration of vasoactive hormones. Changes in hemodynamics and hormone concentration may consequently change renal sodium and water handling.

The nitric oxide system plays a central role in both renal sodium and water handling and regulation of vascular tone and blood pressure.

The effects of tolvaptan the circulation and kidneys is investigated by using measurements of biomarkers specific for the sodium/water balance in the urine and by measurements of vasoactive hormones in the blood after administration of tolvaptan and L-NMMA infusion.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Holstebro, Denmark, 7500
        • Safa Therwani

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Men and women, age 18-40 years
  • Body Mass Index (BMI) 18,5-30 kg/m2

Exclusion Criteria:

  • Anamnestic or clinical signs of heart, lung, lever, kidney and brain disease
  • Neoplastic disease
  • Drug abuse
  • Alcohol abuse
  • Medical treatment except peroral anticontraceptive
  • Pregnancy
  • Smoking
  • Abnormal blood and urine sample
  • Abnormal ECG
  • Blood donation within a month before examination
  • Arterial hypertension (>140 mmHg systolic and/or 90 mmHg diastolic)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tolvaptan
Oral administration of 15 mg Tolvaptan on each examination day.
Drug: Tolvaptan
15 mg pr day for 1 day
Other Names:
  • Samsca
Placebo Comparator: Placebo
Oral administration of 15 mg Unikalk tablet on each examination day.
Drug: Placebo
1 tablet Unikalk 1 pr day for 1 day
Other Names:
  • Unikalk

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CH2O
Time Frame: 5-6 Hours
Measurement of H2O clearance at baseline, during and after L-NMMA infusion.
5-6 Hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Augmentation Index
Time Frame: 5-6 Hours
5-6 Hours
Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)
Time Frame: 5-6 Hours
5-6 Hours
Fractional sodium excretion
Time Frame: 5-6 Hours
Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.
5-6 Hours
Urine biomarkers(Aquaporins, Epithelial Sodium Channels γ and β, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter)
Time Frame: 5-6 Hours
5-6 Hours
Central blood pressure
Time Frame: 5-6 Hours
5-6 Hours
Pulse wave velocity
Time Frame: 5-6 Hours
5-6 Hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regional Hospital Holstebro

Investigators

  • Principal Investigator: Safa Therwani, Bachelor, Medicinsk Forskning

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

March 1, 2014

Study Registration Dates

First Submitted

July 6, 2012

First Submitted That Met QC Criteria

July 9, 2012

First Posted (Estimate)

July 12, 2012

Study Record Updates

Last Update Posted (Estimate)

October 9, 2014

Last Update Submitted That Met QC Criteria

October 8, 2014

Last Verified

October 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAFA-1-2012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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