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

Regional Hospital Holstebro

Status and phase: Completed; Phase 2

Conditions: Nephropathy

Treatments: Drug: Placebo; Drug: 15 mg tolvaptan; Drug: 45 mg tolvaptan; Drug: 30 mg tolvaptan

Study type: Interventional

Funder types: Other

Identifiers

NCT02078973

SAFA-1-2014

2013-003800-38 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 15 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

---

15 participants in 4 patient groups, including a placebo group

15 mg tolvaptan

Active Comparator group

Description:

Oral administration of 15 mg tolvaptan on each examination day.

Treatment:

Drug: 15 mg tolvaptan

30 mg tolvaptan

Active Comparator group

Description:

Oral administration of 30 mg tolvaptan on each examination day.

Treatment:

Drug: 30 mg tolvaptan

45 mg tolvaptan

Active Comparator group

Description:

Oral administration of 45 mg tolvaptan on each examination day.

Treatment:

Drug: 45 mg tolvaptan

Placebo

Placebo Comparator group

Description:

Oral administration of a Unikalk tablet

Treatment:

Drug: Placebo