Clinical trial NCT03803124: Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD
Official title: Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polycystic Kidney, Autosomal Dominant
Keywords: CYSTS, KIDNEYS
Lead sponsor: Regional Hospital Holstebro
Sponsor class: OTHER
First posted: 2019-01-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Renal plasma flow (RPF)
timeFrame: Two hours after trial medicine intake
Secondary outcomes:
measure: Central and brachial blood pressures (BP)
timeFrame: Measured every 15 minutes during the examination day
measure: Glomerular filtration rate (GFR)
timeFrame: Two hours after trial medicine intake
measure: Filtration fraction (FF)
timeFrame: Two hours after trial medicine intake
measure: Plasma concentration of vasopressin (p-AVP)
timeFrame: Measured before and 3 hours after trial medicine intake
measure: Plasma concentration of aldosterone (p-Aldo)
timeFrame: Measured before and 3 hours after trial medicine intake
measure: Plasma concentration of angiotensin II (p-AngII)
timeFrame: Measured before and 3 hours after trial medicine intake
measure: Plasma concentration of renin (PRC)
timeFrame: Measured before and 3 hours after trial medicine intake
measure: Urine excretion of aquaporin 2 (u-AQP2)
timeFrame: Measured before and 3 hours after trial medicine intake
measure: Urine output (OU)
timeFrame: Measured before and 3 hours after trial medicine intake
measure: Urine osmolality (U-osm)
timeFrame: measured before and 3 hours after trial medicine intake
measure: Fractional excretion of sodium (FENa)
timeFrame: Measured before and 3 hours after trial medicine intake
measure: Albumin excretion rate
timeFrame: Measured before and 3 hours after trial medicine intake
Other outcomes:
Locations:
city: Holstebro
country: Denmark
facility: Departments of medical research and medicine
Study officials:
affiliation: Departments of medical research and medicine
name: Frank Mose, MD, Ph D
role: PRINCIPAL_INVESTIGATOR
References: