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

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 Central Hemodynamics During Baseline Conditions and After Inhibition of the Nitric Oxide System in Patients With Autosomal Dominant Polycystic Kidney Disease

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) in patients with autosomal dominant polycystic kidney disease.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

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

      • Holstebro, Denmark, 7500
        • Department of Medical Research and Medicine, Holstebro Regional Hospital

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 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Caucasian men and women
  2. Age between 18-65 years
  3. ADPKD, diagnosed by genetic testing of PKD1 (>85%) or PKD2 mutations, or by ultrasonography:

    1. patients with negative family history for ADKPD and more than 10 cysts in each kidney and no extrarenal or renal findings that suggest causes to cyst formation.
    2. patients with positive family history for ADPKD:

      • 15-39 yr of age and at least 3 or more unilateral or bilateral.
      • 40-59 yr of age and 2 or more cysts in each kidney.
      • 60 yr of age and at least 4 cysts in each kidney.
  4. Kidney function corresponding to CKD stages 1-3(eGFR> 30 mL/min/1,73 m2),
  5. BMI between 18.5 and 35.5 kg/m2.

Exclusion Criteria:

  1. Clinical signs of diseases in the heart, lungs, endocrine organs, brain or neoplastic disease,
  2. clinically significant abnormalities in blood or urine sample at the inclusion
  3. previous cerebrovascular insults,
  4. previous clinical evidence for aneurysm
  5. Alcohol or drug abuse,
  6. smoking,
  7. pregnancy or breastfeeding,
  8. clinically significant changes in the electrocardiogram,
  9. medication except antihypertensive agents and oral contraceptives,
  10. blood pressure>170/105 mmHg despite treatment with metoprolol and/or amlodipine.

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: 60 mg Tolvaptan
Oral administration of 60 mg tolvaptan on each examination day.
60 mg Tolvaptan pr day for 1 day
Other Names:
  • Samsca
Placebo Comparator: Placebo
Oral administration of a Unikalk tablet.
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 (Measurement of H2O clearance)
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.

Investigators

  • Study Chair: Erling B Pedersen, Department of Medical Research and Medicine, Holstebro Regional Hospital Holstebro, Holstebro, Denmark, 7500

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.

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)

February 1, 2015

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

February 18, 2015

First Submitted That Met QC Criteria

August 17, 2015

First Posted (Estimate)

August 19, 2015

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

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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