Effect of the Aquaretic Tolvaptan on Nitric Oxide System

Phase 2

Completed

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

• Registration Number: NCT02527863
• Lead Sponsor: Regional Hospital Holstebro

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-02
• Study First Submitted: 2015-02-18
• Study First Submitted QC: 2015-08-17
• Study First Posted: 2015-08-19
• Primary Completion: 2016-08
• Study Completion: 2016-08
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-28
• Last Update Posted: 2017-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Caucasian men and women

2. Age between 18-65 years

3. ADPKD, diagnosed by genetic testing of PKD1 (>85%) or PKD2 mutations, or by ultrasonography:

   1. 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.

   2. 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.

4. Kidney function corresponding to CKD stages 1-3(eGFR> 30 mL/min/1,73 m2),

5. BMI between 18.5 and 35.5 kg/m2.

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Oral administration of a Unikalk tablet.
60 mg Tolvaptan	Tolvaptan	Oral administration of 60 mg tolvaptan on each examination day.

Primary Outcome Measures

Name	Time	Method
CH2O (Measurement of H2O clearance)	5-6 Hours	Measurement of H2O clearance at baseline, during and after L-NMMA infusion

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Medical Research and Medicine, Holstebro Regional Hospital; 🇩🇰 Holstebro, Denmark