Effect of the Aquaretic Tolvaptan on Nitric Oxide System

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

— TOPO  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527863
• Other study ID #: SAFA-2-2014
• Secondary ID: 2014-001973-15
• Status: Completed
• Phase: Phase 2
• First received: February 18, 2015
• Last updated: February 28, 2017
• Start date: February 2015
• Est. completion date: August 2016

Study information

• Verified date: February 2017
• Source: Regional Hospital Holstebro
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Tolvaptan
60 mg Tolvaptan pr day for 1 day
• Placebo
1 tablet Unikalk pr day for 1 day

Locations

Country	Name	City	State
Denmark	Department of Medical Research and Medicine, Holstebro Regional Hospital	Holstebro

Sponsors (2)

Lead Sponsor	Collaborator
Regional Hospital Holstebro	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CH2O (Measurement of H2O clearance)	Measurement of H2O clearance at baseline, during and after L-NMMA infusion	5-6 Hours
Secondary	Urine biomarkers(Aquaporins and Epithelial Sodium Channels ?)		5-6 Hours
Secondary	Central and brachial blood pressure		5-6 Hours
Secondary	Augmentation Index		5-6 Hours
Secondary	Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)		5-6 Hours
Secondary	Fractional sodium excretion	Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.	5-6 Hours