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

Phase 3

Completed

• Conditions: Polycystic Kidney, Autosomal Dominant
• Interventions: Drug: Placebo; Drug: Tolvaptan

• Registration Number: NCT03803124
• Lead Sponsor: Regional Hospital Holstebro

Brief Summary

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.

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 Timeline

• Study Start: 2015-12
• Primary Completion: 2017-12-15
• Study Completion: 2017-12-15
• Status Verified: 2019-01
• Study First Submitted: 2019-01-07
• Study First Submitted QC: 2019-01-10
• Last Update Submitted: 2019-01-10
• Study First Posted: 2019-01-14
• Last Update Posted: 2019-01-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo 1 tablet before renography
Tolvaptan	Tolvaptan	Drug: Tolvaptan 1 tablet before renography

Primary Outcome Measures

Name	Time	Method
Renal plasma flow (RPF)	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)

Secondary Outcome Measures

Name	Time	Method
Plasma concentration of renin (PRC)	Measured before and 3 hours after trial medicine intake	Blood samples (unit of measurement= pg/ml)
Urine output (OU)	Measured before and 3 hours after trial medicine intake	Urine sample (unit of measurement= ml/min)
Central and brachial blood pressures (BP)	Measured every 15 minutes during the examination day	Measured using Mobil-O-Graph® PWA (unit of measurement= mmHg)
Plasma concentration of vasopressin (p-AVP)	Measured before and 3 hours after trial medicine intake	Blood samples (unit of measurement= pg/ml)
Filtration fraction (FF)	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= %)
Plasma concentration of angiotensin II (p-AngII)	Measured before and 3 hours after trial medicine intake	Blood samples (unit of measurement= pg/ml)
Glomerular filtration rate (GFR)	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)
Plasma concentration of aldosterone (p-Aldo)	Measured before and 3 hours after trial medicine intake	Blood samples (unit of measurement= pmol/ml)
Urine excretion of aquaporin 2 (u-AQP2)	Measured before and 3 hours after trial medicine intake	Urine sample (unit of measurement= ng/ml)
Urine osmolality (U-osm)	measured before and 3 hours after trial medicine intake	Urine sample (unit of measurement= mosmol/kg)
Albumin excretion rate	Measured before and 3 hours after trial medicine intake	Blood and urine sample (unit of measurement= mg/min)
Fractional excretion of sodium (FENa)	Measured before and 3 hours after trial medicine intake	Blood and urine sample (unit of measurement= %)

Trial Locations

Locations (1)

Departments of medical research and medicine; 🇩🇰 Holstebro, Denmark