The Role of Vasopressin Antagonism on Renal Sodium Handling

April 9, 2019 updated by: Jonathan S. Williams, MD, MMSc, Brigham and Women's Hospital
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Vasopressin's potential roles in maintaining normal volume homeostasis are expanding. While previous data support the concept that vasopressin's primary role is in mediating water homeostasis, recent data suggest that vasopressin, through its V2 receptor, may also modulate sodium homeostasis. This effect occurs via activation of the epithelial sodium channel (ENaC). These studies document that vasopressin via activation of the V2 receptor, not only reduces free water excretion but also sodium excretion. These data suggest that blocking this receptor under the right circumstances and in the right population may be effective in modulating hypertension in humans: specifically a V2 receptor antagonist may be effective in treating some individuals that have salt-sensitive hypertension. The current proposal will test in normal human subjects the proof of principle of the above stated hypothesis, and to assess the best markers to determine such an effect. It is important to perform studies with strict environmental control in a clinical research center because of the variability of environmental factors that can create confusion in interpreting data (dietary sodium, activity, body posture, diurnal variation, ambient temperature, sleep-wake cycle, etc.).

The overall program objective is to determine if a vasopressin V2 antagonist will be an effective treatment for salt-sensitive hypertension and if so, what subtype. The object of this specific proposal is to determine the effect of a selective V2 antagonist on sodium handling in normal subjects.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • - 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

Exclusion Criteria:

  • - 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Tolvaptan Oral Tablet
Tolvaptan, to block V2R
Experimental: 15mg Tolvaptan
Drug: Tolvaptan Oral Tablet
Tolvaptan, to block V2R
Experimental: 30mg Tolvaptan
Drug: Tolvaptan Oral Tablet
Tolvaptan, to block V2R

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute intravenous saline response
Time Frame: 6 hours
Urine sodium excretion measured in response to saline infusion
6 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dietary salt response
Time Frame: 6 days
Cumulative sodium excretion measured in response to dietary salt loading
6 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Otsuka Pharmaceutical Co., Ltd.

Investigators

  • Principal Investigator: Jonathan S Williams, MD, MMSc, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2012

Primary Completion (Actual)

September 30, 2014

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

April 9, 2019

First Submitted That Met QC Criteria

April 9, 2019

First Posted (Actual)

April 10, 2019

Study Record Updates

Last Update Posted (Actual)

April 10, 2019

Last Update Submitted That Met QC Criteria

April 9, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012P000638

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Sharing Time Frame

October 2019 for 1 year

IPD Sharing Supporting Information Type

  • Study Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Healthy

Clinical Trials on Tolvaptan Oral Tablet

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Peru

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe