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

Phase 2

Completed

• Conditions: Nephropathy
• Interventions: Drug: 15 mg tolvaptan; Drug: 45 mg tolvaptan; Drug: Placebo; Drug: 30 mg tolvaptan

• Registration Number: NCT02078973
• Lead Sponsor: Regional Hospital Holstebro

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-01
• Study First Submitted: 2014-03-01
• Study First Submitted QC: 2014-03-01
• Study First Posted: 2014-03-05
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-28
• Last Update Posted: 2017-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
15 mg tolvaptan	15 mg tolvaptan	Oral administration of 15 mg tolvaptan on each examination day.
45 mg tolvaptan	45 mg tolvaptan	Oral administration of 45 mg tolvaptan on each examination day.
Placebo	Placebo	Oral administration of a Unikalk tablet
30 mg tolvaptan	30 mg tolvaptan	Oral administration of 30 mg tolvaptan on each examination day.

Primary Outcome Measures

Name	Time	Method
CH2O	5-6 Hours	Measurement of H2O clearance at baseline, during and after L-NMMA infusion

Secondary Outcome Measures

Name	Time	Method
Central and brachial blood pressure	5-6 Hours
Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)	5-6 Hours
Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)	5-6 Hours
Fractional sodium excretion	5-6 Hours	Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.
Augmentation Index	5-6 Hours

Trial Locations

Locations (1)

Department of medical research; 🇩🇰 Holstebro, Denmark