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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)
Sponsored by
Esther Meijer
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  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.

Sites / Locations

  • UMC GroningenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

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

First Posted
March 3, 2020
Last Updated
November 4, 2020
Sponsor
Esther Meijer
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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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

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
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.
Time Frame
Baseline, week 2, week 4, week 6, week 8.
Title
Quality of life, assesed by using the NADIQ-questionnaire.
Description
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.
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
No
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
Email
esther.meijer@umcg.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Iris Koorevaar, drs.
Phone
0031503614198
Email
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
No

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

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