Treatment of Vascular Stiffness in ADPKD

NCT ID: NCT05228574

Last Updated: 2025-08-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-11
• Study Completion Date: 2025-06-18

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

Conditions

Autosomal Dominant Polycystic Kidney

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

High-salt group (group 1)

All participants will be subjected to a low-salt diet (3.5 grams/day) for six weeks.

Group 1 will receive sodium chloride capsules (6 grams/day) for four weeks. In the last two weeks of the trial, all participants will be treated with amiloride tablets (20 mg daily) in open-label setting.

Group Type: ACTIVE_COMPARATOR

No interventions assigned to this group

Low-salt group (group 2)

All participants will be subjected to a low-salt diet (3.5 grams/day) for six weeks.

Group 2 will receive placebo capsules (6 grams/day) for four weeks. In the last two weeks of the trial, all participants will be treated with amiloride tablets (20 mg daily) in open-label setting.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Placebo capsules, 6 grams per day for 4 weeks.

Amiloride Hcl 5mg Tab

Intervention Type: DRUG

Amiloride 5mg tablets, 20 mg per day for two weeks in open-label setting.

Interventions

Sodium chloride (NaCl)

Sodium chloride capsules 6 grams per day for 4 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo capsules, 6 grams per day for 4 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Amiloride Hcl 5mg Tab

Amiloride 5mg tablets, 20 mg per day for two weeks in open-label setting.

Intervention Type: DRUG

Other Intervention Names

Table salt; Amiloride

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: lead

Responsible Party

dr. M. Salih

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

M. Salih, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

Erasmus University Medical Centre Rotterdam

Rotterdam, South Holland, Netherlands

Countries

Netherlands

References

St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Reference Type: DERIVED

PMID: 39356039 (View on PubMed)

Other Identifiers

NL72836.340.10

Identifier Type: -

Identifier Source: org_study_id