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

Cardiovascular Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01638663
• Other study ID #: SAFA-1-2012
• Status: Completed
• Phase: Phase 2
• First received: July 6, 2012
• Last updated: October 8, 2014
• Start date: May 2012
• Est. completion date: March 2014

Study information

• Verified date: October 2014
• Source: Regional Hospital Holstebro
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Nephropathy

Intervention

Drug:
• Tolvaptan
15 mg pr day for 1 day
• Placebo
1 tablet Unikalk 1 pr day for 1 day

Locations

Country	Name	City	State
Denmark	Safa Therwani	Holstebro

Sponsors (1)

Lead Sponsor	Collaborator
Regional Hospital Holstebro

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CH2O	Measurement of H2O clearance at baseline, during and after L-NMMA infusion.	5-6 Hours	No
Secondary	Urine biomarkers(Aquaporins, Epithelial Sodium Channels ? and ß, Sodium/Chloride and Sodium/Potassium/Chloride cotransporter)		5-6 Hours	No
Secondary	Central blood pressure		5-6 Hours	No
Secondary	Pulse wave velocity		5-6 Hours	No
Secondary	Augmentation Index		5-6 Hours	No
Secondary	Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)		5-6 Hours	No
Secondary	Fractional sodium excretion	Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.	5-6 Hours	No