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

Effect of the Aquaretic Tolvaptan on Nitric Oxide System

Sponsors

Lead sponsor: Regional Hospital Holstebro

Collaborator: Aarhus University Hospital

Source 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.

Overall Status Completed
Start Date February 2015
Completion Date August 2016
Primary Completion Date August 2016
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
CH2O (Measurement of H2O clearance) 5-6 Hours
Secondary Outcome
Measure Time Frame
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
Enrollment 18
Condition
Intervention

Intervention type: Drug

Intervention name: Tolvaptan

Description: 60 mg Tolvaptan pr day for 1 day

Arm group label: 60 mg Tolvaptan

Other name: Samsca

Intervention type: Drug

Intervention name: Placebo

Description: 1 tablet Unikalk pr day for 1 day

Arm group label: Placebo

Other name: Unikalk

Eligibility

Criteria:

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.

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Erling B Pedersen Study Chair Department of Medical Research and Medicine, Holstebro Regional Hospital Holstebro, Holstebro, Denmark, 7500
Location
facility Department of Medical Research and Medicine, Holstebro Regional Hospital
Location Countries

Denmark

Verification Date

February 2017

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Regional Hospital Holstebro

Investigator full name: Erling Bjerregaard Pedersen

Investigator title: Professor, MD, Dr.Sci.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: 60 mg Tolvaptan

Arm group type: Active Comparator

Description: Oral administration of 60 mg tolvaptan on each examination day.

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: Oral administration of a Unikalk tablet.

Acronym TOPO
Study Design Info

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov