Effect of the Aquaretic Tolvaptan on Nitric Oxide System

NCT02527863 | Completed Phase 2 DMC

• 2 other identifiers: SAFA-2-20142014-001973-15
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autosomal Dominant Polycystic Kidney Disease

Keywords

Tolvaptan; L-NMMA; ADPKD

Outcome Measures

Primary Outcomes (1)

• CH2O (Measurement of H2O clearance)

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

  5-6 Hours

Secondary Outcomes (5)

• Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)

  5-6 Hours

• Central and brachial blood pressure

  5-6 Hours

• Augmentation Index

  5-6 Hours

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

  5-6 Hours

• Fractional sodium excretion

  5-6 Hours

Study Arms (2)

60 mg Tolvaptan

ACTIVE COMPARATOR

Oral administration of 60 mg tolvaptan on each examination day.

Drug: Tolvaptan

Placebo

PLACEBO COMPARATOR

Oral administration of a Unikalk tablet.

Drug: Placebo

Interventions

Tolvaptan DRUG

60 mg Tolvaptan pr day for 1 day

Also known as: Samsca

60 mg Tolvaptan

Placebo DRUG

1 tablet Unikalk pr day for 1 day

Also known as: Unikalk

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• yr of age and at least 3 or more unilateral or bilateral.
• yr of age and 2 or more cysts in each kidney.
• 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.

You may not qualify if:

• Clinical signs of diseases in the heart, lungs, endocrine organs, brain or neoplastic disease,
• 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.

Sponsors & Collaborators

• Regional Hospital Holstebro: lead
• Aarhus University Hospital: collaborator

Study Sites (1)

Department of Medical Research and Medicine, Holstebro Regional Hospital

Holstebro, Holstebro, 7500, Denmark

Location

Related Publications (2)

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

  PMID: 39356039 DERIVED

• Al Therwani S, Malmberg MES, Rosenbaek JB, Bech JN, Pedersen EB. Effect of tolvaptan on renal handling of water and sodium, GFR and central hemodynamics in autosomal dominant polycystic kidney disease during inhibition of the nitric oxide system: a randomized, placebo-controlled, double blind, crossover study. BMC Nephrol. 2017 Aug 15;18(1):268. doi: 10.1186/s12882-017-0686-3.

  PMID: 28810844 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Erling B Pedersen

  Department of Medical Research and Medicine, Holstebro Regional Hospital Holstebro, Holstebro, Denmark, 7500

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, Dr.Sci.

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: August 19, 2015
• Study Start: February 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: March 1, 2017

Record last verified: 2017-02

Locations

DK (1)