search
Back to results

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

Primary Purpose

Nephropathy

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
15 mg tolvaptan
30 mg tolvaptan
45 mg tolvaptan
Placebo
Sponsored by
Regional Hospital Holstebro
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nephropathy focused on measuring Tolvaptan, L-NMMA, Healthy subjects, Nephrology

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts 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)

Sites / Locations

  • Department of medical research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

15 mg tolvaptan

30 mg tolvaptan

45 mg tolvaptan

Placebo

Arm Description

Oral administration of 15 mg tolvaptan on each examination day.

Oral administration of 30 mg tolvaptan on each examination day.

Oral administration of 45 mg tolvaptan on each examination day.

Oral administration of a Unikalk tablet

Outcomes

Primary Outcome Measures

CH2O
Measurement of H2O clearance at baseline, during and after L-NMMA infusion

Secondary Outcome Measures

Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)
Central and brachial blood pressure
Augmentation Index
Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)
Fractional sodium excretion
Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.

Full Information

First Posted
March 1, 2014
Last Updated
February 28, 2017
Sponsor
Regional Hospital Holstebro
Collaborators
Aarhus University Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT02078973
Brief Title
Effect of the Aquaretic Tolvaptan on Nitric Oxide System. A Dose-response Study (DOVA)
Acronym
DOVA
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
March 1, 2014 (Actual)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Regional Hospital Holstebro
Collaborators
Aarhus University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nephropathy
Keywords
Tolvaptan, L-NMMA, Healthy subjects, Nephrology

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
15 mg tolvaptan
Arm Type
Active Comparator
Arm Description
Oral administration of 15 mg tolvaptan on each examination day.
Arm Title
30 mg tolvaptan
Arm Type
Active Comparator
Arm Description
Oral administration of 30 mg tolvaptan on each examination day.
Arm Title
45 mg tolvaptan
Arm Type
Active Comparator
Arm Description
Oral administration of 45 mg tolvaptan on each examination day.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral administration of a Unikalk tablet
Intervention Type
Drug
Intervention Name(s)
15 mg tolvaptan
Other Intervention Name(s)
Samsca
Intervention Description
15 mg pr day for 1 day
Intervention Type
Drug
Intervention Name(s)
30 mg tolvaptan
Other Intervention Name(s)
Samsca
Intervention Description
30 mg pr day for 1 day
Intervention Type
Drug
Intervention Name(s)
45 mg tolvaptan
Other Intervention Name(s)
Samsca
Intervention Description
45 mg pr day for 1 day
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Unikalk
Intervention Description
1 tablet Unikalk pr day for 1 day
Primary Outcome Measure Information:
Title
CH2O
Description
Measurement of H2O clearance at baseline, during and after L-NMMA infusion
Time Frame
5-6 Hours
Secondary Outcome Measure Information:
Title
Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)
Time Frame
5-6 Hours
Title
Central and brachial blood pressure
Time Frame
5-6 Hours
Title
Augmentation Index
Time Frame
5-6 Hours
Title
Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)
Time Frame
5-6 Hours
Title
Fractional sodium excretion
Description
Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.
Time Frame
5-6 Hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank H Mose, MD, PhD
Organizational Affiliation
Department of medical research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of medical research
City
Holstebro
ZIP/Postal Code
7500
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
28288570
Citation
Al Therwani S, Rosenbaek JB, Mose FH, Bech JN, Pedersen EB. Effect of tolvaptan on renal water and sodium excretion and blood pressure during nitric oxide inhibition: a dose-response study in healthy subjects. BMC Nephrol. 2017 Mar 13;18(1):86. doi: 10.1186/s12882-017-0501-1.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs