Wishing to Decrease Aquaresis in ADPKD Patients Treated With a V2Ra; the Effect of Regulating Protein and Salt
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- 24-hour urine volume
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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/1.73m
- •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;
- •b. Patients having concomitant illnesses likely to confound endpoint assessments (e.g. diabetes mellitus for which medication is needed or diabetes insipidus).
- •Women who are pregnant or breastfeeding.
- •Patients with a blood pressure over 160/100 mm Hg at baseline.
Arms & Interventions
Low salt, low protein treatment period
Double placebo
Intervention: Placebo comparator (protein) (Dietary Supplement)
Low salt, normal protein treatment period
Placebo / 40 grams of protein daily
Intervention: Protein (Dietary Supplement)
Low salt, normal protein treatment period
Placebo / 40 grams of protein daily
Intervention: Placebo comparator (salt) (Dietary Supplement)
Low salt, low protein treatment period
Double placebo
Intervention: Placebo comparator (salt) (Dietary Supplement)
Normal salt, low protein treatment period
6 grams of sodium chloride daily / Placebo
Intervention: Sodiumchloride (Dietary Supplement)
Normal salt, low protein treatment period
6 grams of sodium chloride daily / Placebo
Intervention: Placebo comparator (protein) (Dietary Supplement)
Normal salt, normal protein treatment period
6 grams of sodium chloride daily / 40 grams of protein daily
Intervention: Sodiumchloride (Dietary Supplement)
Normal salt, normal protein treatment period
6 grams of sodium chloride daily / 40 grams of protein daily
Intervention: Protein (Dietary Supplement)
Outcomes
Primary Outcomes
24-hour urine volume
Time Frame: 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 Outcomes
- Serum copeptin levels(Baseline, week 2, week 4, week 6, week 8.)
- mGFR(Baseline, week 2, week 4, week 6, week 8.)
- Blood pressure(Baseline, week 2, week 4, week 6, week 8.)
- Quality of life, assesed by using the ADPKD-IS questionnaire.(Baseline, week 2, week 4, week 6, week 8.)
- Quality of life, assesed by using the NADIQ-questionnaire.(Baseline, week 2, week 4, week 6, week 8.)
Investigators
Esther Meijer
Principal Investigator, nephrologist
University Medical Center Groningen