Clinical trial NCT05228574: Treatment of Vascular Stiffness in ADPKD
Official title: Treatment of Vascular Stiffness in Patients With Autosomal Dominant Polycystic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Autosomal Dominant Polycystic Kidney
Keywords: Polycystic kidney disease
Amiloride
Salt
Hypertension
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2022-02-08
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single-centre, randomized, double-blinded, and placebo-controlled clinical trial with a secondary open-label part.
Primary purpose: TREATMENT

Brief summary: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by cystic kidneys and caused by mutations in the polycystic kidney disease and other rare genes. It is associated with salt-sensitive hypertension, which accounts for the majority of morbidity and mortality. About 70% of patients with ADPKD develop hypertension, prior to the onset of kidney function decline. Early onset hypertension, despite its treatment, is independently associated with rapid kidney function decline. The investigators hypothesize that a high-sodium diet in patients with ADPKD is required for the development of vascular stiffness, which precedes hypertension, and that treatment with amiloride reverses this phenomenon.

Detailed description: Objective of the study:

The investigators aim to investigate if arterial stiffness is exacerbated due to a high-salt diet in patients with ADPKD. The investigators also aim to explore whether treatment with amiloride prevents the arterial stiffness caused by a high-salt diet.

Study design:

Randomized, double blinded and placebo-controlled clinical trial with open-label treatment with amiloride

Study population:

Adults with ADPKD with an estimated glomerular filtration rate (CKD-EPI) of ≥ 60 ml/min/1.73m2

Intervention:

All participants will be subjected to a low-salt diet (3,5 grams/day) throughout the study for a total of 6 weeks. After a run-in period of 2 weeks, participants will be randomized into two treatment groups:

Group 1: Sodium chloride capsules (6 grams/day) for 2 weeks, combined with amiloride (20 mg/day) in last 2 weeks Group 2: Placebo capsules for 2 weeks, combined with amiloride (20 mg/day) in last 2 weeks.

Primary study parameters/outcome of the study:

The three primary outcomes of this study are a difference in central arterial stiffness (pulse wave velocity, PWV) between:

1. The high-salt group versus low-salt group;
2. The high-salt group: before versus after amiloride treatment;
3. The low-salt group: before versus after amiloride treatment.

The burden of participation includes:

* A dietary salt restriction of 3.5 grams/day for a total period of 6 weeks
* Salt supplementation or placebo for a total period of 4 weeks
* Drug intervention with amiloride during the last 2 weeks
* Hospital visits

Eligibility criteria: Inclusion Criteria:

* Adults with typical ADPKD diagnosed based on Ravine criteria and/or a documented Pkd 1 or 2 mutation
* Chronic kidney disease epidemiology collaboration equation estimated glomerular filtration rate ≥60 ml/min/1.73m2
* Ability to provide informed consent

Exclusion Criteria:

* Uncontrolled hypertension, defined as an office blood pressure of ≥160/ ≥90 mmHg with or without antihypertensive treatment
* Concomitant use of ≥ 3 antihypertensive medications
* When antihypertensive treatment is prescribed for any other treatment indication than hypertension (e.g. cardia arrhythmia)
* Serum potassium levels \>5.5 mmol/L (measured within last 6 months)
* History of liver disease (excluding liver cysts due to ADPKD)
* History of heart failure (cardiac ejection fraction \< 35%) or cardiac arrhythmia
* History of diabetes mellitus
* Active infection or antibiotic therapy
* Immunosuppressive therapy within the last year
* Concomitant use of drugs that could influence blood pressure and/or disease progression (Tolvaptan/non-steroidal anti-inflammatory drugs (NSAIDs)/chemotherapy), excluding \< 3 antihypertensive drugs
* Actual pregnancy or unwillingness to adhere to reproductive precautions during the duration of the study

Primary outcomes:
measure: Arterial stiffness induced by high salt diet
timeFrame: At week 3, week 5
measure: Effect of treatment with amiloride on arterial stiffness in high-salt group
timeFrame: At week 5 and at week 7
measure: Effect of treatment with amiloride on arterial stiffness in low-salt group
timeFrame: At week 5 and at week 7
Secondary outcomes:
measure: Blood pressure
timeFrame: At week 3, week 5 and at at week 7
measure: Salt tasting thresholds
timeFrame: At inclusion, week 3, week 5 and at week 7
measure: Skin sodium accumulation
timeFrame: At week 3, week 5 and at week 7
measure: Markers of (vascular) inflammation and endothelial dysfunction
timeFrame: At inclusion, week 3, week 5 and at week 7
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Centre Rotterdam
state: South-Holland
Study officials:
affiliation: Erasmus Medical Center
name: M. Salih, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: