Randomized Cross-Over Study of Fesoterodine on Urgency Episodes in Parkinson's Disease Population
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Urgency episodes
研究概览
简要总结
Parkinson's disease (PD) causes several non-motor autonomic symptoms including lower urinary tract dysfunction. Their symptoms can be managed with antimuscarinics with variable efficacy. Fesoterodine offers a new therapeutic molecule to target the symptoms of urinary frequency, urgency and nocturia in this patient population. The purpose of this protocol is to compare the impact of fesoterodine to placebo on urinary urgency and nocturnal sleep problems in a heterogeneous population of PD patients in a cross-over fashion.
A representative number of patients with baseline overactive bladder (OAB) symptoms and Parkinson's disease will be recruited to receive either the active drug or placebo for the first phase of eight weeks. The groups will then be crossed-over during the second phase of eight weeks. The main outcomes assessed will be the urgency episodes on a 3-day voiding diary, as well as the nocturnal sleep problems will be the Parkinson's Disease Sleep Scale (PDSS).
详细描述
Study purpose and rationale:
Patients with Parkinson's disease (PD) commonly develop lower urinary tract symptoms as their disease severity progresses. The most frequent symptoms are nocturia (night time urinary frequency), urinary frequency and urgency. (1) The effects on voiding function of levodopa and dopamine agonists for the treatment of motor symptoms in patients with PD are not clearly understood because studies conclude conflicting results. (2) Their overactive bladder (OAB) symptoms are primarily managed with antimuscarinics with variable efficacy, and there is concern for possible heightened central side-effects such as cognitive or motor deterioration in this patient population. (3, 4) Current standard of care for PD patients with lower urinary tract symptoms requires a full evaluation with history and physical exam. This is followed by a microscopic urinalysis, a 3-day bladder diary along with several questionnaires. According to their symptoms, some patients may require a non-invasive uroflowmetry and assessment of post void residual, while others will undergo a full urodynamic studies. Management of their voiding symptoms will require initial conservative measures and behavioral modifications (reducing caffeinated drinks and smoking cessation, optimizing fluid intake, weight loss) and bladder training. If this fails to improve their symptoms, oral pharmacotherapy will be offered with antimuscarinics or beta-3 agonists.
The purpose of this protocol is to compare the impact of fesoterodine to placebo on urinary urgency and nocturnal sleep problems in a heterogeneous population of PD patients in a cross-over fashion. Although OAB can be effectively treated, there is compelling and scientifically sound methodological reasons for its use as participants in the study will not face additional risks of serious or irreversible harm from exposure to placebo. Placebo controlled trials are the most rigorous test of treatment efficacy for evaluating a medical therapy and will require fewer subjects than active control trials. Lastly, anticholinergic studies have shown to have a very large placebo effect and are only partially effective in treating voiding symptoms, which justifies the use of a placebo arm.
Sample size:
This is an initial pilot study to identify the effect size of fesoterodine treatment on urgency episodes in patients with PD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 50-85 years-old
- •self-reported OAB symptoms for ≥3 months
- •a mean of ≥8 micturitions/ 24 hr
- •≥3 urgency episodes/24 hr on a 3-day bladder diary
- •at least "some moderate problems" on the Patient Perception of Bladder Condition (PPBC)
- •Montreal cognitive assessment (MOCA) score ≥24
- •Stable dose of dopaminergic medications and levodopa (between 300 and 1200 mg daily)
排除标准
- •Urinary retention: PVR >150 ml (as assessed by bladder scan)
- •Contra-indications to fesoterodine
- •Unwilling to stop current antimuscarinics
- •Patients on anticholinergics for motor disturbances
- •Dementia based on clinical evaluation
- •Atypical Parkinsonian syndrome
- •Deep brain stimulation
- •Presence of hallucination
研究组 & 干预措施
Placebo
Subjects will be started on placebo tablets, similar to fesoterodine 4 mg, and will have the option to escalate as well.
干预措施: Fesoterodine (Drug)
Placebo
Subjects will be started on placebo tablets, similar to fesoterodine 4 mg, and will have the option to escalate as well.
干预措施: Placebo (Drug)
Fesoterodine
Drug intervention of fesoterodine 4 mg once a day in the morning after the two-week washout period. They will have the option to escalate to 8 mg (2 tablets of 4 mg each) after 4 weeks on fesoterodine. Patients will have the option to go back to one tablet (i.e., 4 mg) at any time in the study.
干预措施: Fesoterodine (Drug)
Fesoterodine
Drug intervention of fesoterodine 4 mg once a day in the morning after the two-week washout period. They will have the option to escalate to 8 mg (2 tablets of 4 mg each) after 4 weeks on fesoterodine. Patients will have the option to go back to one tablet (i.e., 4 mg) at any time in the study.
干预措施: Placebo (Drug)
结局指标
主要结局
Urgency episodes
时间窗: 10 weeks and 20 weeks
Mean change from baseline in number of urgency episodes per 24 hours
次要结局
- Patient's severity of overactive bladder symptoms as measured by OAB-Q score(10 weeks and 20 weeks)
- Patient's perception of his bladder condition as measured by PPBC score(10 weeks and 20 weeks)
- Patient's urgency perception as measured by the UPS score(10 weeks and 20 weeks)
- Cognitive ability as measured by the MOCA score(10 weeks and 20 weeks)
- Safety of fesoterodine in Parkinson's Disease population(10 weeks and 20 weeks)
- Micturitions(10 weeks and 20 weeks)
- Urgency urinary incontinence episodes(10 weeks and 20 weeks)
- Severe urgency episodes(10 weeks and 20 weeks)
- Nocturnal micturitions(10 weeks and 20 weeks)
- Incontinence pads used(10 weeks and 20 weeks)
- Nocturnal sleep disturbances measured by Parkinson's Disease Sleep Scale(10 weeks and 20 weeks)
研究者
Lysanne Campeau, MDCM, PhD, FRCSC
Assistant Professor
Sir Mortimer B. Davis - Jewish General Hospital