Safety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease

NCT ID: NCT06291116

Last Updated: 2024-03-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-01
• Study Completion Date: 2029-05-01

Brief Summary

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease linked to mutation of the PKD1 or PKD2 genes encoding polycystins 1 and 2. Patients develop renal cysts with progressive impairment of renal function leading to renal failure. terminal renal failure for 1/3 of them. These patients also present early with high blood pressure and cardiovascular complications, notably intracerebral aneurysms. This phenotype is linked to abnormal polycystins on the cilia of renal epithelial and vascular endothelial cells which no longer ensure the mechanotransduction of shear forces linked to urinary and blood flow leading to the modification of numerous cellular functions.

Experimental results suggested that stimulation of dopamine receptor type 5 (DR5) could restore the mechanosensitivity of endothelial cells, a hypothesis supported by our first results showing that local administration of dopamine improves endothelial function in patients with ADPKD. through restoration of endothelial NO release upon increased blood flow. Similar positive results on endothelial function and hemodynamics were recently obtained in the IMPROVE-PKD study with rotigotine, a dopamine agonist administered via transdermal patches for 2 months at a low dose (4 mg/24h).

Dopaminergic stimulation could also prevent abnormalities linked to polycystin deficiency at the renal level and we therefore hypothesize that rotigotine could slow the progression of ADPKD both at the renal and cardiovascular levels.

This phase 2 study aims to ensure the good long-term tolerance of rotigotine in patients with ADPKD and to collect preliminary data on its renal impact.

Conditions

Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

experimental

Experimental group: standard care + rotigotine at 4 mg/24 hours for 24 months.

Group Type: EXPERIMENTAL

standard care + rotigotine at 4 mg/24h for 24 months.

Intervention Type: DRUG

standard care + rotigotine at 4 mg/24h for 24 months.

Control

Control group: standard care for 24 months.

Group Type: ACTIVE_COMPARATOR

standard care for 24 months.

Intervention Type: DRUG

standard care for 24 months.

Interventions

standard care + rotigotine at 4 mg/24h for 24 months.

standard care + rotigotine at 4 mg/24h for 24 months.

Intervention Type: DRUG

standard care for 24 months.

standard care for 24 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• ADPKD patients aged 18 to 60 years
• Normotensive or hypertensive patients treated controlled (SBP/DBP on daytime ABPM <135/85 mmHg less than 3 months old)
• Patient having read and understood the information letter and signed the consent form
• Effective contraception in women of childbearing age (for postmenopausal women, a confirmatory diagnosis should be obtained)
• Patient benefiting from a social protection scheme

Exclusion Criteria

• Stage 4 or 5 renal insufficiency (GFR CKD-EPI <30 ml/min)
• Renal transplant patients
• Dialysis patients
• History of myocardial infarction or stroke less than 6 months old
• Severe hepatic insufficiency (Child-Pugh class C)
• Patients currently being treated or treated in the 6 months preceding the trial with a dopamine agonist or antagonist
• Systolic heart failure requiring hospitalization in the 6 months preceding inclusion or known heart failure with an LVEF <30%
• Orthostatic hypotension (decrease > 20 mm Hg)
• Pregnant, breastfeeding woman, or proven absence of contraception
• Excessive alcohol consumption (greater than 20 g/day)
• History of addictive behavior, particularly gambling, compulsive purchasing or hypersexuality
• Drug addiction or suspected illicit drug use
• Taking other sedative medications or other central nervous system depressants (benzodiazepines, antipsychotics, antidepressants or neuroleptics with antiemetic intent)
• Hypersensitivity to the active ingredient, rotigotine, or to one of its excipients
• Known allergy to sulphites
• Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection, or guardianship or curatorship.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

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

2022/0345/HP

Identifier Type: -

Identifier Source: org_study_id