Effect of the Aquaretic Tolvaptan on Nitric Oxide System. A Dose-response Study (DOVA) (DOVA)

February 28, 2017 updated by: Erling Bjerregaard Pedersen, Regional Hospital Holstebro

The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Circulatory System, During Basal Conditions and During Inhibition of the Nitric Oxide System in Healthy Subjects. A Dose-response Study.

Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water and sodium excretion. Inhibition of V2R increases vasopressin concentration in plasma, which stimulates V1-receptors in the vascular bed and may change both central and brachial hemodynamics and plasma concentration of vasoactive hormones.

The purpose of the study is to measure the effects of tolvaptan on renal handling of water and sodium, systemic hemodynamics and vasoactive hormones at baseline and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

15

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
        • Department of medical research

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

Yes

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: 15 mg tolvaptan
Oral administration of 15 mg tolvaptan on each examination day.
Drug: 15 mg tolvaptan
15 mg pr day for 1 day
Other Names:
  • Samsca
Active Comparator: 30 mg tolvaptan
Oral administration of 30 mg tolvaptan on each examination day.
Drug: 30 mg tolvaptan
30 mg pr day for 1 day
Other Names:
  • Samsca
Active Comparator: 45 mg tolvaptan
Oral administration of 45 mg tolvaptan on each examination day.
Drug: 45 mg tolvaptan
45 mg pr day for 1 day
Other Names:
  • Samsca
Placebo Comparator: Placebo
Oral administration of a Unikalk tablet
Drug: Placebo
1 tablet Unikalk 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
Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)
Time Frame: 5-6 Hours
5-6 Hours
Central and brachial blood pressure
Time Frame: 5-6 Hours
5-6 Hours
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

Collaborators and Investigators

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

Sponsor

Regional Hospital Holstebro

Collaborators

Aarhus University Hospital

Investigators

  • Principal Investigator: Frank H Mose, MD, PhD, Department of medical research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

March 1, 2014

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

March 1, 2014

First Submitted That Met QC Criteria

March 1, 2014

First Posted (Estimate)

March 5, 2014

Study Record Updates

Last Update Posted (Actual)

March 1, 2017

Last Update Submitted That Met QC Criteria

February 28, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAFA-1-2014
  • 2013-003800-38 (EudraCT Number)

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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