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

Phase 2

Completed

• Conditions: Cardiovascular Diseases; Nephropathy
• Interventions: Drug: Placebo; Drug: Tolvaptan

• Registration Number: NCT01638663
• Lead Sponsor: Regional Hospital Holstebro

Brief Summary

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.

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 Timeline

• Study Start: 2012-05
• Study First Submitted: 2012-07-06
• Study First Submitted QC: 2012-07-09
• Study First Posted: 2012-07-12
• Primary Completion: 2014-03
• Study Completion: 2014-03
• Status Verified: 2014-10
• Last Update Submitted: 2014-10-08
• Last Update Posted: 2014-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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
Placebo	Placebo	Oral administration of 15 mg Unikalk tablet on each examination day.
Tolvaptan	Tolvaptan	Oral administration of 15 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
Urine biomarkers(Aquaporins, Epithelial Sodium Channels γ and β, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter)	5-6 Hours
Central blood pressure	5-6 Hours
Pulse wave velocity	5-6 Hours
Augmentation Index	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.

Trial Locations

Locations (1)

Safa Therwani; 🇩🇰 Holstebro, Denmark