- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02527863
Effect of the Aquaretic Tolvaptan on Nitric Oxide System (TOPO)
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
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Holstebro, Denmark, 7500
- Department of Medical Research and Medicine, Holstebro Regional Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 60 mg Tolvaptan
Oral administration of 60 mg tolvaptan on each examination day.
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60 mg Tolvaptan pr day for 1 day
Other Names:
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Placebo Comparator: Placebo
Oral administration of a Unikalk tablet.
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1 tablet Unikalk pr day for 1 day
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CH2O (Measurement of H2O clearance)
Time Frame: 5-6 Hours
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Measurement of H2O clearance at baseline, during and after L-NMMA infusion
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5-6 Hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Urine biomarkers(Aquaporins and Epithelial Sodium Channels γ)
Time Frame: 5-6 Hours
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5-6 Hours
|
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Central and brachial blood pressure
Time Frame: 5-6 Hours
|
5-6 Hours
|
|
Augmentation Index
Time Frame: 5-6 Hours
|
5-6 Hours
|
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Vasoactive Hormones( Angiotensin II, Aldosterone, Endothelin, Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Arginin Vasopressin)
Time Frame: 5-6 Hours
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5-6 Hours
|
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Fractional sodium excretion
Time Frame: 5-6 Hours
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Measurement of Sodium excretion at baseline, during and after L-NMMA infusion.
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5-6 Hours
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Erling B Pedersen, Department of Medical Research and Medicine, Holstebro Regional Hospital Holstebro, Holstebro, Denmark, 7500
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Urologic Diseases
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Abnormalities, Multiple
- Kidney Diseases, Cystic
- Ciliopathies
- Kidney Diseases
- Polycystic Kidney Diseases
- Polycystic Kidney, Autosomal Dominant
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Natriuretic Agents
- Antidiuretic Hormone Receptor Antagonists
- Tolvaptan
Other Study ID Numbers
- SAFA-2-2014
- 2014-001973-15 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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