Effect of the Aquaretic Tolvaptan on Nitric Oxide System (TOPO)

Regional Hospital Holstebro

Status and phase: Completed; Phase 2

Conditions: Autosomal Dominant Polycystic Kidney Disease

Treatments: Drug: Tolvaptan; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02527863

2014-001973-15 (EudraCT Number)

SAFA-2-2014

Details and patient eligibility

About

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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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18 participants in 2 patient groups, including a placebo group

60 mg Tolvaptan

Active Comparator group

Description:

Oral administration of 60 mg tolvaptan on each examination day.

Treatment:

Drug: Tolvaptan

Placebo

Placebo Comparator group

Description:

Oral administration of a Unikalk tablet.

Treatment:

Drug: Placebo