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

The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Circulatory System, During Basal Conditions and During Inhibition of the Nitric Oxide System in Healthy Subjects. A Dose-response Study.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02078973

Acronym

DOVA

Enrollment

Registered

2014-03-05

Start date

2014-03-01

Completion date

2016-01-31

Last updated

2017-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Nephropathy

Keywords

Tolvaptan, L-NMMA, Healthy subjects, Nephrology

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).

Interventions

DRUG15 mg tolvaptan

15 mg pr day for 1 day

DRUG30 mg tolvaptan

30 mg pr day for 1 day

DRUG45 mg tolvaptan

45 mg pr day for 1 day

DRUGPlacebo

1 tablet Unikalk pr day for 1 day

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 40 Years

Healthy volunteers

Yes

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)

Design outcomes

Primary

Measure	Time frame	Description
CH2O	5-6 Hours	Measurement of H2O clearance at baseline, during and after L-NMMA infusion

Secondary

Measure	Time frame	Description
Fractional sodium excretion	5-6 Hours	Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.
Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)	5-6 Hours	—
Central and brachial blood pressure	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	—

Countries

Denmark

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 10, 2026