Clinical trial NCT04310319: Wishing to Decrease Aquaresis in ADPKD Patients Treated With a V2Ra; the Effect of Regulating Protein and Salt
Official title: Wishing to Decrease Aquaresis in ADPKD Patients Treated With a V2Ra; the Effect of Regulating Protein and Salt
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Polycystic Kidney, Autosomal Dominant
ADPKD
Autosomal Dominant Polycystic Kidney
Keywords: ADPKD
aquaresis
Vasopressine V2 receptor antagonist
Diet
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2020-03-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study evaluates the effect of regulating salt and protein intake on urinevolume in patients with ADPKD treated with a vasopressine V2 receptor antagonist (V2RA). The investigators hypothesize that changing sodium and protein intake will reduce V2RA-induced polyuria.

Detailed description: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the formation of numerous cysts in both kidneys and progressive renal function decline leading to renal replacement therapy (RRT) at a median age of 58 years. The first (and at the moment only) drug to slow down renal function decline, is a vasopressin V2 receptor antagonist (V2RA). This medicament slows renal function decline by 26 to 34%. V2RA also causes aquaresis associated side-effects such as polyuria of \>6 liter per day in the majority of patients. These side-effects limit wide spread use among ADPKD-patients. Therefore, there is a need to improve its tolerability. While using a V2RA, urine concentrating ability is strongly diminished. Therefore, urine volume is largely determined by total osmolar excretion. This is a well-known fact in nephrogenic diabetes insipidus, a disease with clear pathophysiological similarities to treatment with a vasopressin V2 receptor antagonist (a defect receptor versus pharmacological blockade). A recent study found osmolar excretion to be associated with urinary volume during V2RA treatment. Whether a change in osmolar load changes polyuria during V2RA has not yet been investigated. The investigators hypothesize that changing sodium and protein intake will reduce polyuria.

Eligibility criteria: Inclusion criteria:

1. Diagnosis of ADPKD (ravine criteria/documented by nephrologist)
2. Stable treatment regimen of tolvaptan as part of routine clinical care in the highest dose tolerable (preferably 120 mg daily), with a urine osmolality lower than 250 mosmol/L.
3. Age \>= 18 years.
4. eGFR \>30 ml/min/1.73m2.
5. Providing informed consent.
6. Compliance to the recommended diet at two consecutive times.

Exclusion criteria:

1. Patients who, in the opinion of the investigator may present a safety risk.
2. Patients who are unlikely to adequately comply to the trial's procedures (due for instance to medical conditions likely to require interruption or discontinuation, history of substance abuse or non-compliance).
3. a. Patients taking medication likely to confound endpoint assessments:

   * lithium in any dosing regimen;
   * chronic use of systemic corticosteroids in any dosage;
   * chronic use of any diuretics in any dosing regimen;
   * daily use of any NSAIDs in any dosing regimen;

3. b. Patients having concomitant illnesses likely to confound endpoint assessments (e.g. diabetes mellitus for which medication is needed or diabetes insipidus).

4. Women who are pregnant or breastfeeding. 5. Patients with a blood pressure over 160/100 mm Hg at baseline.

Primary outcomes:
measure: 24-hour urine volume
timeFrame: Baseline, week 2, week 4, week 6, week 8.
Secondary outcomes:
measure: Serum copeptin levels
timeFrame: Baseline, week 2, week 4, week 6, week 8.
measure: mGFR
timeFrame: Baseline, week 2, week 4, week 6, week 8.
measure: Blood pressure
timeFrame: Baseline, week 2, week 4, week 6, week 8.
measure: Quality of life, assesed by using the ADPKD-IS questionnaire.
timeFrame: Baseline, week 2, week 4, week 6, week 8.
measure: Quality of life, assesed by using the NADIQ-questionnaire.
timeFrame: Baseline, week 2, week 4, week 6, week 8.
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: UMC Groningen
Study officials:
affiliation: Universitar Medical Centre Groningen
name: Esther Meijer, Dr.
role: PRINCIPAL_INVESTIGATOR
References: