NCT03910231

Brief Summary

Vasopressin has primarily been considered to be a water and osmosis regulating hormone that mediates its effects on renal aquaporin channels. Recent data suggest that vasopressin, through its V2 receptor, may also modulate sodium homeostasis. The purpose of this human physiology study was to test whether antagonism of the V2R alters urine sodium excretion in normal healthy volunteers.

Trial Health

100
On Track

Trial Health Score

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

Enrollment
30

participants targeted

Target at P25-P50 for phase_1 healthy

Timeline
Completed

Started Feb 2012

Longer than P75 for phase_1 healthy

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

Study Start

First participant enrolled

February 1, 2012

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2014

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2015

Completed
4.2 years until next milestone

First Submitted

Initial submission to the registry

April 9, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 10, 2019

Completed
Last Updated

April 10, 2019

Status Verified

April 1, 2019

Enrollment Period

2.7 years

First QC Date

April 9, 2019

Last Update Submit

April 9, 2019

Conditions

Healthy

Keywords

vasopressin receptorrenal sodium excretion

Outcome Measures

Primary Outcomes (1)

  • Acute intravenous saline response

    Urine sodium excretion measured in response to saline infusion

    6 hours

Secondary Outcomes (1)

  • Dietary salt response

    6 days

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Tolvaptan Oral Tablet

15mg Tolvaptan

EXPERIMENTAL

15mg Tolvaptan

Drug: Tolvaptan Oral Tablet

30mg Tolvaptan

EXPERIMENTAL

30mg Tolvaptan

Drug: Tolvaptan Oral Tablet

Interventions

Tolvaptan Oral TabletDRUG

Tolvaptan, to block V2R

15mg Tolvaptan30mg TolvaptanPlacebo

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • \- Blood pressure \<130/85 mmHg and \>100/50 mmHg
  • Normal laboratory values for (see "Normal Values" table):
  • Complete blood count
  • Serum creatinine, sodium, potassium, glucose, liver enzymes
  • Urinalysis
  • ECG

You may not qualify if:

  • \- Alcohol intake \>12 oz per week
  • Tobacco or recreational drug use
  • History of coronary disease, diabetes, hypertension, stroke, kidney disease, or illness requiring overnight hospitalization in the past 6 months
  • Any prescription medication or herbal medication use except oral contraceptive or multivitamin
  • Pregnancy or current breastfeeding
  • First degree relative with hypertension, diabetes, stroke, renal or cardiac disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (5)

  • Stockand JD. Vasopressin regulation of renal sodium excretion. Kidney Int. 2010 Nov;78(9):849-56. doi: 10.1038/ki.2010.276. Epub 2010 Aug 25.

    PMID: 20736986BACKGROUND

  • Bankir L, Bichet DG, Bouby N. Vasopressin V2 receptors, ENaC, and sodium reabsorption: a risk factor for hypertension? Am J Physiol Renal Physiol. 2010 Nov;299(5):F917-28. doi: 10.1152/ajprenal.00413.2010. Epub 2010 Sep 8.

    PMID: 20826569BACKGROUND

  • Blanchard A, Frank M, Wuerzner G, Peyrard S, Bankir L, Jeunemaitre X, Azizi M. Antinatriuretic effect of vasopressin in humans is amiloride sensitive, thus ENaC dependent. Clin J Am Soc Nephrol. 2011 Apr;6(4):753-9. doi: 10.2215/CJN.06540810. Epub 2011 Jan 13.

    PMID: 21233458BACKGROUND

  • Gheorghiade M, Niazi I, Ouyang J, Czerwiec F, Kambayashi J, Zampino M, Orlandi C; Tolvaptan Investigators. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation. 2003 Jun 3;107(21):2690-6. doi: 10.1161/01.CIR.0000070422.41439.04. Epub 2003 May 12.

    PMID: 12742979BACKGROUND

  • Hauptman PJ, Zimmer C, Udelson J, Shoaf SE, Mallikaarjun S, Bramer SL, Orlandi C. Comparison of two doses and dosing regimens of tolvaptan in congestive heart failure. J Cardiovasc Pharmacol. 2005 Nov;46(5):609-14. doi: 10.1097/01.fjc.0000180899.24865.b6.

    PMID: 16220067BACKGROUND

MeSH Terms

Interventions

Tolvaptan

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Jonathan S Williams, MD, MMSc

    Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
Blinding to investigator, participant and study staff. Randomization assignment and blinding provided by Investigational Drug Services
Purpose
OTHER
Intervention Model
PARALLEL
Model Details: Randomized, placebo-controlled, double-blinded, parallel arm clinical trial
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

April 9, 2019

First Posted

April 10, 2019

Study Start

February 1, 2012

Primary Completion

September 30, 2014

Study Completion

February 1, 2015

Last Updated

April 10, 2019

Record last verified: 2019-04

Data Sharing

IPD Sharing
Will share
Shared Documents
STUDY PROTOCOL
Time Frame
October 2019 for 1 year