Treatment of Vascular Stiffness in ADPKD

NCT05228574 | Completed Phase 4

• 1 other identifier: NL72836.340.10
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Autosomal Dominant Polycystic Kidney

Keywords

Polycystic kidney disease; Amiloride; Salt; Hypertension

Outcome Measures

Primary Outcomes (3)

• Arterial stiffness induced by high salt diet

  Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), in high-salt group versus low-salt group.

  At week 3, week 5

• Effect of treatment with amiloride on arterial stiffness in high-salt group

  Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), before versus after amiloride treatment in high-salt group.

  At week 5 and at week 7

• Effect of treatment with amiloride on arterial stiffness in low-salt group

  Difference in central arterial stiffness, measured as the pulse wave velocity (PWV), before versus after amiloride treatment in low-salt group.

  At week 5 and at week 7

Secondary Outcomes (4)

• Blood pressure

  At week 3, week 5 and at at week 7

• Salt tasting thresholds

  At inclusion, week 3, week 5 and at week 7

• Skin sodium accumulation

  At week 3, week 5 and at week 7

• Markers of (vascular) inflammation and endothelial dysfunction

  At inclusion, week 3, week 5 and at week 7

Study Arms (2)

High-salt group (group 1)

ACTIVE COMPARATOR

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.

Low-salt group (group 2)

PLACEBO COMPARATOR

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.

Dietary Supplement: Placebo; Drug: Amiloride Hcl 5mg Tab

Interventions

Sodium chloride (NaCl) DIETARY_SUPPLEMENT

Sodium chloride capsules 6 grams per day for 4 weeks.

Also known as: Table salt

Placebo DIETARY_SUPPLEMENT

Placebo capsules, 6 grams per day for 4 weeks.

Low-salt group (group 2)

Amiloride Hcl 5mg Tab DRUG

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

Also known as: Amiloride

Low-salt group (group 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus University Medical Centre Rotterdam

Rotterdam, South Holland, 3015GD, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 39356039 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Polycystic Kidney Diseases; Hypertension

Interventions

Sodium Chloride; Sodium Chloride, Dietary; Amiloride

Condition Hierarchy (Ancestors)

Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Sodium, Dietary; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• M. Salih, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a single-centre, randomized, double-blinded, and placebo-controlled clinical trial with a secondary open-label part.

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: February 8, 2022
• Study Start: March 11, 2022
• Primary Completion: June 18, 2025
• Study Completion: June 18, 2025
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)