Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD (POLY)

January 10, 2019 updated by: Erling Bjerregaard Pedersen, Regional Hospital Holstebro
Polycystic kidney disease (ADPKD) is a common genetic disorder, characterized by the formation of cysts in the kidneys, causing gradual renal function-loss. Previous studies have shown that, reduced glomerular filtration rate (GFR) and renal plasma flow (RPF) play a role in the progression of renal disease in ADPKD. Tolvaptan is a vasopressin 2 antagonist, which seems to reduce the growth of total kidney volume (TKV) and the decline in e-GFR in ADPKD. The mechanism is not fully understood and could, at least partly, be caused by stimulation of the renal blood flow. The purpose of this trial is to investigate if tolvaptan´s improve renal blood flow and glomerular filtration in ADPKD, in a randomized, cross-over, double-blind, placebo-controlled study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The aim is to measure the acute effects of tolvaptan on:

  1. Renal hemodynamics (RPF, GFR, filtration fraction ((FF)) and renovascular resistance ((RVR))
  2. Blood pressure (central blood pressure ((cBP)) and brachial blood pressure bBP)
  3. Several vasoactive hormones (plasma renin ((PRC)), plasma angiotensin II ((p-Ang-II)), plasma aldosterone ((p-Aldo)), plasma vasopressin ((p-AVP))

in patients with ADPKD.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Holstebro, Denmark, 7500
        • Departments of Medical Research and Medicine

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > 18 years
  • Diagnosis with ADPKD
  • Informed consent
  • Contraception for fertile women

Exclusion Criteria:

  • Renal transplantation
  • Operation in the kidney
  • Diabetes mellitus
  • Neoplastic conditions
  • Pregnancy, nursing
  • Unwillingness to participate
  • eGFR > 30
  • Intolerance towards tolvaptan
  • Alcohol or medical abuse,
  • BP >>170/110 blood pressure despite regulation

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Tolvaptan

Drug: Tolvaptan

1 tablet before renography
Drug: Tolvaptan
1 tablet before renography
Placebo Comparator: Placebo

Placebo

1 tablet before renography
Drug: Placebo
1 tablet before renography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal plasma flow (RPF)
Time Frame: Two hours after trial medicine intake
Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min)
Two hours after trial medicine intake

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central and brachial blood pressures (BP)
Time Frame: Measured every 15 minutes during the examination day
Measured using Mobil-O-Graph® PWA (unit of measurement= mmHg)
Measured every 15 minutes during the examination day
Glomerular filtration rate (GFR)
Time Frame: Two hours after trial medicine intake
Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min)
Two hours after trial medicine intake
Filtration fraction (FF)
Time Frame: Two hours after trial medicine intake
Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= %)
Two hours after trial medicine intake
Plasma concentration of vasopressin (p-AVP)
Time Frame: Measured before and 3 hours after trial medicine intake
Blood samples (unit of measurement= pg/ml)
Measured before and 3 hours after trial medicine intake
Plasma concentration of aldosterone (p-Aldo)
Time Frame: Measured before and 3 hours after trial medicine intake
Blood samples (unit of measurement= pmol/ml)
Measured before and 3 hours after trial medicine intake
Plasma concentration of angiotensin II (p-AngII)
Time Frame: Measured before and 3 hours after trial medicine intake
Blood samples (unit of measurement= pg/ml)
Measured before and 3 hours after trial medicine intake
Plasma concentration of renin (PRC)
Time Frame: Measured before and 3 hours after trial medicine intake
Blood samples (unit of measurement= pg/ml)
Measured before and 3 hours after trial medicine intake
Urine excretion of aquaporin 2 (u-AQP2)
Time Frame: Measured before and 3 hours after trial medicine intake
Urine sample (unit of measurement= ng/ml)
Measured before and 3 hours after trial medicine intake
Urine output (OU)
Time Frame: Measured before and 3 hours after trial medicine intake
Urine sample (unit of measurement= ml/min)
Measured before and 3 hours after trial medicine intake
Urine osmolality (U-osm)
Time Frame: measured before and 3 hours after trial medicine intake
Urine sample (unit of measurement= mosmol/kg)
measured before and 3 hours after trial medicine intake
Fractional excretion of sodium (FENa)
Time Frame: Measured before and 3 hours after trial medicine intake
Blood and urine sample (unit of measurement= %)
Measured before and 3 hours after trial medicine intake
Albumin excretion rate
Time Frame: Measured before and 3 hours after trial medicine intake
Blood and urine sample (unit of measurement= mg/min)
Measured before and 3 hours after trial medicine intake

Collaborators and Investigators

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

Sponsor

Regional Hospital Holstebro

Investigators

  • Principal Investigator: Frank Mose, MD, Ph D, Departments of Medical Research and Medicine

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)

December 1, 2015

Primary Completion (Actual)

December 15, 2017

Study Completion (Actual)

December 15, 2017

Study Registration Dates

First Submitted

January 7, 2019

First Submitted That Met QC Criteria

January 10, 2019

First Posted (Actual)

January 14, 2019

Study Record Updates

Last Update Posted (Actual)

January 14, 2019

Last Update Submitted That Met QC Criteria

January 10, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FHM-1-2015

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.

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