Safety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease

NCT06291116 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2022/0345/HP
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is caused by mutations in the PKD1 or PKD2 genes, which encode polycystins 1 and 2. Patients develop renal cysts associated with a progressive decline in kidney function, ultimately leading to end-stage renal disease in approximately one third of cases. ADPKD is also characterized by early-onset hypertension and cardiovascular complications, notably intracranial aneurysms. This phenotype is related to abnormal polycystin function in the primary cilia of renal epithelial and vascular endothelial cells, resulting in impaired mechanotransduction of shear stress induced by urinary and blood flow and subsequent alterations in multiple cellular functions. Experimental studies have suggested that stimulation of dopamine receptor type 5 (DR5) may restore endothelial mechanosensitivity. This hypothesis is supported by our preliminary results showing that local administration of dopamine improves endothelial function in patients with ADPKD through restoration of nitric oxide (NO) release in response to increased blood flow. Consistent with these findings, the IMPROVE-PKD study recently demonstrated similar beneficial effects on endothelial function and hemodynamics using rotigotine, a dopamine agonist administered via transdermal patches for two months at a low dose (4 mg/24 h). Dopaminergic stimulation may also prevent renal abnormalities related to polycystin deficiency. We therefore hypothesize that rotigotine could slow the progression of ADPKD at both the renal and cardiovascular levels. This phase 2 study aims to evaluate the long-term tolerability of rotigotine in patients with ADPKD and to collect preliminary data on its effects on renal outcomes.

Conditions

Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety and tolerability of rotigotine administered at a dose of 4 mg/24h for 24 months in patients with ADPKD

  Safety is defined by the occurrence of adverse events (AvE) and the occurrence of serious adverse events (SvA) for 24 months. The main safety criterion is based on the proportion of participants who experienced at least one EvIG during the 24 months of study follow-up such as the occurrence of serious reactions at the application site or certain behavioral disorders.

  throught 24 months

Study Arms (2)

experimental

EXPERIMENTAL

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

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

Control

ACTIVE COMPARATOR

Control group: standard care for 24 months.

Drug: standard care for 24 months.

Interventions

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

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

experimental

standard care for 24 months. DRUG

standard care for 24 months.

Control

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University Hospital, Rouen: lead

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

Kidney Diseases

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 4, 2024
• Study Start: March 1, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share