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

Polycystic Kidney, Autosomal Dominant Clinical Trial

— POLY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03803124
• Other study ID #: FHM-1-2015
• Status: Completed
• Phase: Phase 3
• Start date: December 2015
• Est. completion date: December 15, 2017

Study information

• Verified date: January 2019
• Source: Regional Hospital Holstebro
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 15, 2017
• Est. primary completion date: December 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

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

Locations

Country	Name	City	State
Denmark	Departments of medical research and medicine	Holstebro

Sponsors (1)

Lead Sponsor	Collaborator
Regional Hospital Holstebro

Country where clinical trial is conducted

Denmark, 

Outcome

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