Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Continuous Subcutaneous Infusion in Parkinson's Disease Patients With Refractory Visual Hallucinations
试验速览
- 阶段
- 2 期
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Clinical Global Impression of Severity
研究概览
简要总结
This randomised, double-blind, placebo-controlled trial will evaluate the efficacy of continuous apomorphine infusion compared to placebo in PD patients with visual hallucinations, inadequately controlled with clozapine and cholinesterase inhibitors.
详细描述
Introduction Visual hallucinations occur frequently in Parkinson's disease (PD). The prevalence of visual hallucinations ranges from 22 to 38%, increasing after long-term follow-up to more than 60%. Risk factors for visual hallucinations are age, disease duration, and cognitive impairment. The treatment of visual hallucinations is cumbersome and options are limited. Only clozapine has been proven to be efficacious without deteriorating the motor symptoms of PD. Instead of oral dopamine agonists and rotigotine, continuous infusion of apomorphine is well-tolerated in PD patients with cognitive impairments and/or visual hallucinations. Even beneficial effect of apomorphine on visual hallucinations are suggested, however there is lack of a randomized controlled trial.
The purpose of this randomised, double-blind, placebo-controlled trial is to evaluate the efficacy of continuous apomorphine infusion compared to placebo in PD patients with visual hallucinations, inadequately controlled with clozapine and cholinesterase inhibitors.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female and male subjects aged ≥30;
- •Diagnosis of established PD, defined by the Movement Disorders Society PD criteria (Postuma et al., 2015);
- •Presence of visual severe hallucinations defined as more than 3 times a week (van Laar et al., 2010);
- •Visual hallucinations must have developed after PD diagnosis;
- •Visual hallucinations must have been optimally treated with reduction of dopamine agonists if possible, and prescription of clozapine and/or cholinesterase inhibitors if needed;
- •Female subjects must complaint with a highly effective contraceptive method (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method) during the study, if sexually active;
- •Subjects should be able and capable of adhering to the protocol, visit schedules, and medication intake according to the judgement of the investigator.
排除标准
- •Symptomatic, clinically relevant and medically uncontrolled orthostatic hypotension;
- •Patients with a prolonged QT interval corrected for heart rate according to Bazett's formula (QTc) of >450 ms for male and >470 ms for female at screening, or history of a long QT syndrome;
- •PD medication change (i.e., dopamine-agonists, amantadine, monoamine oxidase (MAO)-B inhibitors, anticholinergics and cholinesterase inhibitors) in last month prior to initiation (van Laar et al., 2010);
- •Active psychosis or a history of significant psychosis;
- •Any medical condition that is likely to interfere with an adequate participation in the study including e.g. current diagnosis of unstable epilepsy, clinically relevant cardiac dysfunction and/or myocardial infarction or stroke within the last 12 months.
研究组 & 干预措施
Apomorphine
This arm will be treated with continuous subcutaneous infusion of apomorphine. The infusion will start with 1 mg/hr during the waking day (approximately 16 hours). The flow rate will be adjusted on a weekly basis, and may be increased with 0.5 to 1.0 mg/hr per discretion of the investigator, aiming at the disappearance of visual hallucinations. The duration of treatment is 4 weeks.
干预措施: Apomorphine (Drug)
Placebo
This arm will be treated with continuous subcutaneous infusion of placebo. The infusion will start with 1 mg/hr during the waking day (approximately 16 hours). The flow rate will be adjusted on a weekly basis, and may be increased with 0.5 to 1.0 mg/hr per discretion of the investigator aiming at the disappearance of visual hallucinations. The duration of treatment is 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Clinical Global Impression of Severity
时间窗: Four weeks
Clinical Global Impression of Severity questionnaire
次要结局
- Apathy(Four weeks)
- Clinical Global Impression of Improvement(Four weeks)
- Motor complications(Four weeks)
- Sleeping problems(Four weeks)
- Neuropsychiatric symptoms(Four weeks)
- Visual perception(Four weeks)
- Cognition(Four weeks)
- Anxiety(Four weeks)
- Visual Hallucinations(Four weeks)
- Quality of Life(Four weeks)
- Depression(Four weeks)
- Motor symptoms(Four weeks)
- Attention(Four weeks)
研究者
Teus van Laar
MD PhD
University Medical Center Groningen