Evaluation of the Effect of Botulinum Toxin on Resting Tremor of the Refractory Upper Limb in Parkinsonians, Cross-over Study, Double Blind and Placebo-controlled
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- The effect of botulinum toxin on the resting tremor of the upper limb refractory to treatments
研究概览
简要总结
Tremor is one of the most common symptoms in Parkinson Disease (PD), affecting almost 60% of patients. There is currently no specific treatment for tremor in PD, and 30% of patients develop drug-resistant tremor, making its management more complex. Botulinum toxin (BT) is widely used in neurology, but few studies have been carried out on the effect of BT in parkinsonian tremor without consensus on its management in parkinsonian patients. In this study, we therefore propose to evaluate the effect of BT injected using precision medicine in the treatment of refractory resting tremor in patients with PD, compared with placebo injection.
详细描述
Parkinson's disease (PD) is the second most common neurodegenerative disease. Tremor is one of the most common symptoms, affecting almost 60% of patients. It has a considerable impact on their quality of life, causing psychosocial stress in over 25% of patients. There is currently no specific treatment for tremor in PD, and 30% of patients develop drug-resistant tremor, making its management more complex. Botulinum toxin (BT) has been approved in France in 1994 and is widely used in neurology. To date, few studies have been carried out on the effect of BT in parkinsonian tremor: most have been open-label and have mixed parkinsonian patients and patients with essential tremor. Therefore, there is no consensus on the management of tremor in patients with PD. Nevertheless, there is a real need for treatment of refractory tremor, particularly in elderly patients, patients who cannot tolerate high doses of medication or patients who are ineligible for neurostimulation. In this study, we therefore propose to evaluate the effect of BT injected using precision medicine in the treatment of refractory resting tremor in parkinsonian patients, compared with placebo injection. We hypothesize that BT treatment improves parkinsonian tremor in a clinically relevant way compared to placebo injection using an optimized and personalized injection technique (doses of toxin and muscles injected). The drug will be injected intramuscularly into the muscles identified as responsible for the tremor, by an investigator specialising in injections. PD patients with resistant tremor will be included and followed up in this study for one year. BT or placebo will be injected at 6 months apart in all patients thanks to the cross over study design.
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, Investigator)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with PD defined according to UKPDSBB criteria;
- •Men and women aged between 40 and 80 years;
- •Patients with troublesome rest tremor assessed by the CGI-S scale ≥ 3 and persistent despite the initiation of ≥ two anti-parkinsonian treatments (levodopa, dopaminergic agonist, anticholinergic), which defines drug-resistant parkinsonian tremor;
- •Patients naïve to botulinum toxin treatment;
- •Patients whose antiparkinsonian treatment has been stable for at least 4 weeks prior to inclusion and for the duration of the study;
- •Person affiliated with or beneficiary of a social security scheme;
- •Free, informed, and written consent signed by the participant and the investigator (no later than the day of inclusion and before any examination required by the research).
排除标准
- •Patients with tremors related to a pathology other than PD;
- •Patients with atypical parkinsonian syndrome;
- •Patients treated with drugs which have the adverse effect of causing the appearance or aggravation of tremors: lithium, sodium valproate, levetiracetam, benzodiazepines, corticosteroids, thyroid hormones, ciclosporin, alcohol, tricyclic antidepressants, theophillyne, terbutaline, antipsychotics (excluding clozapine) ;
- •Patients with hypersensitivity to the active substance or to one of the excipients (human albumin, lactulose);
- •patients with atrophy of the target muscle
- •patients with a urinary tract infection at the time of treatment if the patient suffers from urinary incontinence due to neurological detrusor overactivity
- •patients with a history of swallowing or respiratory disorders;
- •patients with marked clinical or subclinical neuromuscular transmission deficits (e.g., myasthenia gravis);
- •patients with fixed contractures Pregnant or breastfeeding women;
- •Women of childbearing age without effective contraception;
- •Patients under legal guardianship, tutorship, or curatorship.
研究组 & 干预措施
Botulinum toxin followed by placebo arm
In this cross-over study, the patient will be his or her own control. The patient will receive both treatments at 6 months apart: DYSPORT followed by the placebo (the order of injections has been randomly assigned).
干预措施: Injection of Dysport then placebo (Drug)
Placebo followed by botulinum toxin arm
In this cross-over study, the patient will be his or her own control. The patient will receive both treatments at 6 months apart: placebo followed by DYSPORT (the order of injections has been randomly assigned).
干预措施: Injection of placebo then Dysport (Drug)
结局指标
主要结局
The effect of botulinum toxin on the resting tremor of the upper limb refractory to treatments
时间窗: 7,5 months
It will be assessed by the PGI-C (Patient Global Impression-Change) score completed by the patient six weeks after injection and compared between treatments.
次要结局
- The effect of botulinum toxin on the resting tremor: evolution evaluated by the investigator(7,5 months)
- The effect of botulinum toxin on the resting tremor: severity evaluated by the investigator(7,5 months)
- The effect of botulinum toxin on the resting tremor: amplitude evaluated by the investigator(7,5 months)
- The effect of botulinum toxin on the resting tremor: patient-assessed severity(7,5 months)
- The effect of botulinum toxin on the postural tremor: evolution evaluated by the investigator(7,5 months)
- The effect of botulinum toxin on the postural tremor: severity evaluated by the investigator(7,5 months)
- The effect of botulinum toxin on the postural tremor: amplitude evaluated by the investigator(7,5 months)
- The effect of botulinum toxin on the postural tremor: patient-assessed change(7,5 months)
- The effect of botulinum toxin on the postural tremor: patient-assessed severity(7,5 months)
- The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): duration(12 months)
- The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): amplitude(7,5 months)
- The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): frequency(7,5 months)
- The effect of botulinum toxin on the patient's experience: life quality(7,5 months)
- The effect of botulinum toxin on the patient's experience: daily life activities(7,5 months)
- The safety of use for botulinum toxin: muscle weakness (1)(7,5 months)
- The safety of use for botulinum toxin: muscle weakness (2)(7,5 months)
- The safety of use for botulinum toxin: adverse events(12 months)