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NCT Number: NCT02527863

Effect of the Aquaretic Tolvaptan on Nitric Oxide System

Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water and sodium excretion. Inhibition of V2R increases vasopressin concentration in plasma, which stimulates V1-receptors in the vascular bed and may change both central and brachial hemodynamics and plasma concentration of vasoactive hormones.

The purpose of the study is to measure the effects of tolvaptan on renal handling of water and sodium, systemic hemodynamics and vasoactive hormones at baseline and during nitric oxide (NO)-inhibition with L-NG-monomethyl-arginine (L-NMMA) in patients with autosomal dominant polycystic kidney disease.

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Key information

Conditions

Autosomal Dominant Polycystic Kidney Disease Abnormalities, Multiple Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Kidney Diseases Kidney Diseases, Cystic Male Urogenital Diseases Polycystic Kidney Diseases Polycystic Kidney, Autosomal Dominant Urogenital Diseases Urologic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Department of Medical Research and Medicine, Holstebro Regional Hospital

Holstebro, 7500, Denmark

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Caucasian men and women
  • Age between 18-65 years
  • ADPKD, diagnosed by genetic testing of PKD1 (>85%) or PKD2 mutations, or by ultrasonography:
  • patients with negative family history for ADKPD and more than 10 cysts in each kidney and no extrarenal or renal findings that suggest causes to cyst formation.
  • patients with positive family history for ADPKD:
  • 15-39 yr of age and at least 3 or more unilateral or bilateral.
  • 40-59 yr of age and 2 or more cysts in each kidney.
  • 60 yr of age and at least 4 cysts in each kidney.
  • Kidney function corresponding to CKD stages 1-3(eGFR> 30 mL/min/1,73 m2),
  • BMI between 18.5 and 35.5 kg/m2.

Exclusion criteria

  • Clinical signs of diseases in the heart, lungs, endocrine organs, brain or neoplastic disease,
  • clinically significant abnormalities in blood or urine sample at the inclusion
  • previous cerebrovascular insults,
  • previous clinical evidence for aneurysm
  • Alcohol or drug abuse,
  • smoking,
  • pregnancy or breastfeeding,
  • clinically significant changes in the electrocardiogram,
  • medication except antihypertensive agents and oral contraceptives,
  • blood pressure>170/105 mmHg despite treatment with metoprolol and/or amlodipine.

Treatment and study plan

Tolvaptan

Drug

60 mg Tolvaptan pr day for 1 day

Other names: Samsca

Placebo

Drug

1 tablet Unikalk pr day for 1 day

Other names: Unikalk

Primary outcomes

  1. CH2O (Measurement of H2O clearance)

    Time frame: 5-6 Hours

    Measurement of H2O clearance at baseline, during and after L-NMMA infusion

Secondary outcomes

  1. Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)

    Time frame: 5-6 Hours

  2. Central and brachial blood pressure

    Time frame: 5-6 Hours

  3. Augmentation Index

    Time frame: 5-6 Hours

  4. Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)

    Time frame: 5-6 Hours

  5. Fractional sodium excretion

    Time frame: 5-6 Hours

    Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.

Sponsors and collaborators

Lead sponsor

Regional Hospital Holstebro

Other

Collaborators

  • Aarhus University Hospital

Registry information

Official study title

The Effects of Tolvaptan on Renal Handling of Water and Sodium, Vasoactive Hormones and Central Hemodynamics During Baseline Conditions and After Inhibition of the Nitric Oxide System in Patients With Autosomal Dominant Polycystic Kidney Disease

Acronym: TOPO

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Aug 19, 2015
Registry last updated
Mar 1, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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