Safety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

Study 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.

Eligibility

Primary outcome measure(s)

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

Trial sites (4)

More University Hospital, Rouen trials in France

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