Safety of RotigotiNe in Patients With Autosomal Dominant Polycystic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 4
- 主要终点
- Evaluate the safety and tolerability of rotigotine administered at a dose of 4 mg/24h for 24 months in patients with ADPKD
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Control
Control group: standard care for 24 months.
干预措施: standard care for 24 months. (Drug)
experimental
Experimental group: standard care + rotigotine at 4 mg/24 hours for 24 months.
干预措施: standard care + rotigotine at 4 mg/24h for 24 months. (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of rotigotine administered at a dose of 4 mg/24h for 24 months in patients with ADPKD
时间窗: 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.
次要结局
未报告次要终点