Skip to main content
OpenTrials
Completed

NCT Number: NCT01638663

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Cardiovascular Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Nephropathy Urogenital Diseases Urologic Diseases

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Safa Therwani

Holstebro, 7500, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Tolvaptan

Drug

15 mg pr day for 1 day

Other names: Samsca

Placebo

Drug

1 tablet Unikalk 1 pr day for 1 day

Other names: Unikalk

Primary outcomes

  1. CH2O

    Time frame: 5-6 Hours

    Measurement of H2O clearance at baseline, during and after L-NMMA infusion.

Secondary outcomes

  1. Urine biomarkers(Aquaporins, Epithelial Sodium Channels γ and β, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter)

    Time frame: 5-6 Hours

  2. Central blood pressure

    Time frame: 5-6 Hours

  3. Pulse wave velocity

    Time frame: 5-6 Hours

  4. Augmentation Index

    Time frame: 5-6 Hours

  5. Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)

    Time frame: 5-6 Hours

  6. Fractional sodium excretion

    Time frame: 5-6 Hours

    Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.

Sponsors and collaborators

Lead sponsor

Regional Hospital Holstebro

Other

Registry information

Official study title

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

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Jul 12, 2012
Registry last updated
Oct 9, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.