Safety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease

Kidney Diseases Clinical Trial

— ETERNAL-PKD  

Official title:

Safety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06291116
• Other study ID #: 2022/0345/HP
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2025
• Est. completion date: May 1, 2029

Study information

• Verified date: February 2024
• Source: University Hospital, Rouen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: May 1, 2029
• Est. primary completion date: May 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Rouen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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