Clinical trial NCT01638663: Effect of the Aquaretic Tolvaptan on Nitric Oxide System (TORA)
Official title: Effect of Vasopressin Antagonism on Renal Sodium and Water Handling and Circulation During Inhibition of the Nitric Oxide System in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiovascular Diseases
Nephropathy
Keywords: Tolvaptan
L-NMMA
Healthy subjects
Nephrology
Cardiology
Lead sponsor: Regional Hospital Holstebro
Sponsor class: OTHER
First posted: 2012-07-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: CH2O
timeFrame: 5-6 Hours
Secondary outcomes:
measure: Urine biomarkers(Aquaporins, Epithelial Sodium Channels γ and β, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter)
timeFrame: 5-6 Hours
measure: Central blood pressure
timeFrame: 5-6 Hours
measure: Pulse wave velocity
timeFrame: 5-6 Hours
measure: Augmentation Index
timeFrame: 5-6 Hours
measure: Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)
timeFrame: 5-6 Hours
measure: Fractional sodium excretion
timeFrame: 5-6 Hours
Other outcomes:
Locations:
city: Holstebro
country: Denmark
facility: Safa Therwani
Study officials:
affiliation: Medicinsk Forskning
name: Safa Therwani, Bachelor
role: PRINCIPAL_INVESTIGATOR
References: