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

Primary Purpose

Polycystic Kidney, Autosomal Dominant, ADPKD, Autosomal Dominant Polycystic Kidney

Status

Unknown status

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

Sodiumchloride

Protein

Placebo comparator (salt)

Placebo comparator (protein)

About this trial

This is an interventional treatment trial for Polycystic Kidney, Autosomal Dominant focused on measuring ADPKD, aquaresis, Vasopressine V2 receptor antagonist, Diet

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Diagnosis of ADPKD (ravine criteria/documented by nephrologist)
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.
Age >= 18 years.
eGFR >30 ml/min/1.73m2.
Providing informed consent.
Compliance to the recommended diet at two consecutive times.

Exclusion criteria:

Patients who, in the opinion of the investigator may present a safety risk.
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).
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.

Sites / Locations

UMC GroningenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Arm Label

Normal salt, low protein treatment period

Normal salt, normal protein treatment period

Low salt, low protein treatment period

Low salt, normal protein treatment period

Arm Description

6 grams of sodium chloride daily / Placebo

6 grams of sodium chloride daily / 40 grams of protein daily

Double placebo

Placebo / 40 grams of protein daily

Outcomes

Primary Outcome Measures

24-hour urine volume

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

Serum copeptin levels

Change in serum copeptin levels, comparing copeptin level measured at baseline with copeptin level measured at the end of each treatment period.

mGFR

Change in measured GFR, comparing mGFR measured at baseline with mGFR measured at the end of each treatment period.

Blood pressure

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.

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.

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.

Full Information

NCT ID

NCT04310319

First Posted

March 3, 2020

Last Updated

November 4, 2020

Sponsor

Esther Meijer

1. Study Identification

Unique Protocol Identification Number

NCT04310319

Brief Title

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

Acronym

WATER

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Unknown status

Study Start Date

September 7, 2020 (Actual)

Primary Completion Date

September 2021 (Anticipated)

Study Completion Date

October 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Esther Meijer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Polycystic Kidney, Autosomal Dominant, ADPKD, Autosomal Dominant Polycystic Kidney

Keywords

ADPKD, aquaresis, Vasopressine V2 receptor antagonist, Diet

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Normal salt, low protein treatment period

Arm Type

Other

Arm Description

6 grams of sodium chloride daily / Placebo

Arm Title

Normal salt, normal protein treatment period

Arm Type

Other

Arm Description

6 grams of sodium chloride daily / 40 grams of protein daily

Arm Title

Low salt, low protein treatment period

Arm Type

Other

Arm Description

Double placebo

Arm Title

Low salt, normal protein treatment period

Arm Type

Other

Arm Description

Placebo / 40 grams of protein daily

Intervention Type

Dietary Supplement

Intervention Name(s)

Sodiumchloride

Intervention Description

Subjects will receive 4 capsules containting 750 NaCl each 2dd, making a total of 6 grams NaCl per day.

Intervention Type

Dietary Supplement

Intervention Name(s)

Protein

Intervention Description

Subjects will receive 2dd 40 ml of a protein beverage containing 0.5 grams of protein per ml, making a total of 40 grams of protein per day.

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo comparator (salt)

Intervention Description

Subjects will receive 4 placebo capsules (identical to salt capsules) 2dd.

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo comparator (protein)

Intervention Description

Subjects will receive 2dd 40 ml of placebo beverage (identical to protein beverage).

Primary Outcome Measure Information:

Title

24-hour urine volume

Description

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.

Time Frame

Baseline, week 2, week 4, week 6, week 8.

Secondary Outcome Measure Information:

Title

Serum copeptin levels

Description

Change in serum copeptin levels, comparing copeptin level measured at baseline with copeptin level measured at the end of each treatment period.

Time Frame

Baseline, week 2, week 4, week 6, week 8.

Title

mGFR

Description

Change in measured GFR, comparing mGFR measured at baseline with mGFR measured at the end of each treatment period.

Time Frame

Baseline, week 2, week 4, week 6, week 8.

Title

Blood pressure

Description

Change in blood pressure, comparing blood pressure measured at baseline with blood pressure measured at the end of each treatment period.

Time Frame

Baseline, week 2, week 4, week 6, week 8.

Title

Quality of life, assesed by using the ADPKD-IS questionnaire.

Description

Time Frame

Baseline, week 2, week 4, week 6, week 8.

Title

Quality of life, assesed by using the NADIQ-questionnaire.

Description

Time Frame

Baseline, week 2, week 4, week 6, week 8.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Diagnosis of ADPKD (ravine criteria/documented by nephrologist) 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. Age >= 18 years. eGFR >30 ml/min/1.73m2. Providing informed consent. Compliance to the recommended diet at two consecutive times. Exclusion criteria: Patients who, in the opinion of the investigator may present a safety risk. 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). 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Meijer, Dr.

Phone

003150 361 6161

esther.meijer@umcg.nl

First Name & Middle Initial & Last Name or Official Title & Degree

Iris Koorevaar, drs.

Phone

0031503614198

i.w.koorevaar@umcg.nl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Esther Meijer, Dr.

Organizational Affiliation

Universitar Medical Centre Groningen

Official's Role

Principal Investigator

Facility Information:

Facility Name

UMC Groningen

City

Groningen

ZIP/Postal Code

9713GZ

Country

Netherlands

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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