NCT02078973

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Mar 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 1, 2014

Completed
Same day until next milestone

Study Start

First participant enrolled

March 1, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 5, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

March 1, 2017

Status Verified

February 1, 2017

Enrollment Period

1.8 years

First QC Date

March 1, 2014

Last Update Submit

February 28, 2017

Conditions

Nephropathy

Keywords

TolvaptanL-NMMAHealthy subjectsNephrology

Outcome Measures

Primary Outcomes (1)

  • CH2O

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

    5-6 Hours

Secondary Outcomes (5)

  • 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

  • Fractional sodium excretion

    5-6 Hours

Study Arms (4)

15 mg tolvaptan

ACTIVE COMPARATOR

Oral administration of 15 mg tolvaptan on each examination day.

Drug: 15 mg tolvaptan

30 mg tolvaptan

ACTIVE COMPARATOR

Oral administration of 30 mg tolvaptan on each examination day.

Drug: 30 mg tolvaptan

45 mg tolvaptan

ACTIVE COMPARATOR

Oral administration of 45 mg tolvaptan on each examination day.

Drug: 45 mg tolvaptan

Placebo

PLACEBO COMPARATOR

Oral administration of a Unikalk tablet

Drug: Placebo

Interventions

15 mg tolvaptanDRUG

15 mg pr day for 1 day

Also known as: Samsca
15 mg tolvaptan
30 mg tolvaptanDRUG

30 mg pr day for 1 day

Also known as: Samsca
30 mg tolvaptan
45 mg tolvaptanDRUG

45 mg pr day for 1 day

Also known as: Samsca
45 mg tolvaptan
PlaceboDRUG

1 tablet Unikalk pr day for 1 day

Also known as: Unikalk
Placebo

Eligibility Criteria

Age18 Years - 40 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Men and women, age 18-40 years
  • Body Mass Index (BMI) 18,5-30 kg/m2

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of medical research

Holstebro, 7500, Denmark

Location

Related Publications (1)

  • 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.

    PMID: 28288570DERIVED

MeSH Terms

Conditions

Kidney Diseases

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Urologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

BenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Frank H Mose, MD, PhD

    Department of medical research

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, MD, Dr.Sci.

Study Record Dates

First Submitted

March 1, 2014

First Posted

March 5, 2014

Study Start

March 1, 2014

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

March 1, 2017

Record last verified: 2017-02

Locations

DK(1)