Wishing to Decrease Aquaresis in ADPKD Patients Treated With a V2Ra; the Effect of Regulating Protein and Salt

Not Applicable

• Conditions: Polycystic Kidney, Autosomal Dominant; ADPKD; Autosomal Dominant Polycystic Kidney
• Interventions: Dietary Supplement: Sodiumchloride; Dietary Supplement: Placebo comparator (salt); Dietary Supplement: Protein; Dietary Supplement: Placebo comparator (protein)

• Registration Number: NCT04310319
• Lead Sponsor: Esther Meijer

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.

Study Timeline

• Study First Submitted: 2020-03-03
• Study First Submitted QC: 2020-03-13
• Study First Posted: 2020-03-17
• Study Start: 2020-09-07
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-04
• Last Update Posted: 2020-11-05
• Primary Completion: 2021-09
• Study Completion: 2021-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Normal salt, low protein treatment period	Sodiumchloride	6 grams of sodium chloride daily / Placebo
Normal salt, normal protein treatment period	Protein	6 grams of sodium chloride daily / 40 grams of protein daily
Low salt, low protein treatment period	Placebo comparator (salt)	Double placebo
Low salt, low protein treatment period	Placebo comparator (protein)	Double placebo
Normal salt, low protein treatment period	Placebo comparator (protein)	6 grams of sodium chloride daily / Placebo
Normal salt, normal protein treatment period	Sodiumchloride	6 grams of sodium chloride daily / 40 grams of protein daily
Low salt, normal protein treatment period	Protein	Placebo / 40 grams of protein daily
Low salt, normal protein treatment period	Placebo comparator (salt)	Placebo / 40 grams of protein daily

Primary Outcome Measures

Name	Time	Method
24-hour urine volume	Baseline, week 2, week 4, week 6, week 8.	Change in 24-hour urine volume as percentage, comparing the mean of the volumes collected during baseline with the mean of the two volumes collected at the end of each treatment period.

Secondary Outcome Measures

Name	Time	Method
Serum copeptin levels	Baseline, week 2, week 4, week 6, week 8.	Change in serum copeptin levels, comparing copeptin level measured at baseline with copeptin level measured at the end of each treatment period.
mGFR	Baseline, week 2, week 4, week 6, week 8.	Change in measured GFR, comparing mGFR measured at baseline with mGFR measured at the end of each treatment period.
Blood pressure	Baseline, week 2, week 4, week 6, week 8.	Change in blood pressure, comparing blood pressure measured at baseline with blood pressure measured at the end of each treatment period.
Quality of life, assesed by using the ADPKD-IS questionnaire.	Baseline, week 2, week 4, week 6, week 8.	Change in reported quality of life, comparing reported quality of life at baseline to reported quality of life at the end of each treatment period. To assess quality of life, the ADPKD-IS questionnaires will be used.
Quality of life, assesed by using the NADIQ-questionnaire.	Baseline, week 2, week 4, week 6, week 8.	Change in reported quality of life, comparing reporter quality of life at baseline to reported quality of life at the end of each treatment period. To assess quality of life, the NADIQ-questionnaires will be used.

Trial Locations

Locations (1)

UMC Groningen; 🇳🇱 Groningen, Netherlands