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 (TOX PARK)
2026年9月10日 更新者：University Hospital, Toulouse
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.
研究概览
详细说明
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.
研究类型
介入性
注册 (估计的)
39
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Clémence Leung, MD
- 电话号码：+33 05 61 77 61 76
- 邮箱：leung.c@chu-toulouse.fr
学习地点
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Nîmes、法国、30 029
- Nîmes University Hospital
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接触：
- Giovanni Castelnovo, MD
- 电话号码：+33 04 66 68 32 63
- 邮箱：giovanni.castelnovo@chu-nimes.fr
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首席研究员：
- Giovanni Castelnovo, MD
-
Toulouse、法国、31 059
- Pierre Paul Riquet Hospital - Toulouse University Hospital
-
接触：
- Clémence Leung, MD
- 电话号码：+33 05 61 77 61 76
- 邮箱：leung.c@chu-toulouse.fr
-
首席研究员：
- Clémence Leung, MD
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：交叉作业
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：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).
|
Both treatments, first DYSPORT 500UI for 6 months then placebo, also for 6 months, will be administered intramuscularly using the same schedule and procedures thus allowing the blind to be maintained.
The two injections will be carried at 6 months apart: the drug will be injected intramuscularly, into the muscles identified as responsible for the tremor, by an investigator specialized in carrying out injections.
The doses injected will depend on the severity of the tremor and the number of muscles injected, which is conditioned by the tremor phenotype.
|
|
实验性的：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).
|
Both treatments, first placebo for 6 months then DYSPORT 500UI, also for 6 months, will be administered intramuscularly using the same schedule and procedures thus allowing the blind to be maintained.
The two injections will be carried at 6 months apart: the drug will be injected intramuscularly, into the muscles identified as responsible for the tremor, by an investigator specialized in carrying out injections.
The doses injected will depend on the severity of the tremor and the number of muscles injected, which is conditioned by the tremor phenotype.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
The effect of botulinum toxin on the resting tremor of the upper limb refractory to treatments
大体时间：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.
|
7,5 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
The effect of botulinum toxin on the resting tremor: evolution evaluated by the investigator
大体时间：7,5 months
|
It will be assessed by the CGI-C (Clinician Global Impression-Change) investigator-level change score, six weeks after injection.
|
7,5 months
|
|
The effect of botulinum toxin on the resting tremor: severity evaluated by the investigator
大体时间：7,5 months
|
It will be assessed by the delta of severity scores at the CGI-S (Clinician Global Impression-Severity) investigator level between injection and six weeks post-injection.
|
7,5 months
|
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The effect of botulinum toxin on the resting tremor: amplitude evaluated by the investigator
大体时间：7,5 months
|
It will be assessed by the delta of the item score 3.17 (amplitude) at the MDS-UPDRS III investigator level between injection and six weeks post-injection.
|
7,5 months
|
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The effect of botulinum toxin on the resting tremor: patient-assessed severity
大体时间：7,5 months
|
It will be assessed by the delta of severity scores at the patient scale PGI-S (Patient Global Impression-Severity) between injection and six weeks post-injection.
|
7,5 months
|
|
The effect of botulinum toxin on the postural tremor: evolution evaluated by the investigator
大体时间：7,5 months
|
It will be assessed by the change score at the CGI-C investigator scale, at six weeks post-injection.
|
7,5 months
|
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The effect of botulinum toxin on the postural tremor: severity evaluated by the investigator
大体时间：7,5 months
|
It will be assessed by the delta of severity scores at the CGI-S investigator level between injection and six weeks post-injection.
|
7,5 months
|
|
The effect of botulinum toxin on the postural tremor: amplitude evaluated by the investigator
大体时间：7,5 months
|
It will be assessed by the delta of item 3.21 (amplitude) at the MDS-UPDRS III investigator level between injection and six weeks post-injection.
|
7,5 months
|
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The effect of botulinum toxin on the postural tremor: patient-assessed change
大体时间：7,5 months
|
It will be assessed by the PGI-C scale score completed by the patient six weeks after injection and compared between groups.
|
7,5 months
|
|
The effect of botulinum toxin on the postural tremor: patient-assessed severity
大体时间：7,5 months
|
It will be assessed by the delta of severity scores on the PGI-S (Patient Global Impression-Severity) scale completed by the patient between the injection and six weeks post-injection.
|
7,5 months
|
|
The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): duration
大体时间：12 months
|
It will be assessed by the proportion of time the patient has a tremor, measured using an actimeter for 7 days prior to the assessment visit.
|
12 months
|
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The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): amplitude
大体时间：7,5 months
|
It will be assessed by the mean angular amplitude measured using motion sensors placed on the hand and arm at six weeks post-injection.
|
7,5 months
|
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The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): frequency
大体时间：7,5 months
|
It will be assessed by the mean frequency in Hertz (Hz) measured using motion sensors placed on the hand and arm at six weeks post-injection.
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7,5 months
|
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The effect of botulinum toxin on the patient's experience: life quality
大体时间：7,5 months
|
It will be assessed by the delta of the patient's quality of life score on the PDQ-39 self-administered questionnaire between injection and six weeks post-injection.
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7,5 months
|
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The effect of botulinum toxin on the patient's experience: daily life activities
大体时间：7,5 months
|
It will be assessed by the delta of the daily life activities score by the MDS-UPDRS scale, parts one and two between injection and six weeks post-injection.
|
7,5 months
|
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The safety of use for botulinum toxin: muscle weakness (1)
大体时间：7,5 months
|
It will be assessed by the delta of the measurement in Newton of the manual dynamometer, for the treated hand, between injection and six weeks after injection.
|
7,5 months
|
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The safety of use for botulinum toxin: muscle weakness (2)
大体时间：7,5 months
|
It will be assessed by the delta of the severity scores for muscle weakness in the treated hand, on the PGI-S (Patient Global Impression Severity) scale, completed by the patient between the injection and six weeks after the injection.
|
7,5 months
|
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The safety of use for botulinum toxin: adverse events
大体时间：12 months
|
It will be assessed by all the adverse events collected during the study.
|
12 months
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
The factors associated with good response to botulinum toxin treatment
大体时间：12 months
|
The correct response to treatment will be determined from the scores of the PGI-S patient scale on the severity of the tremor and on the severity of the muscle weakness.
|
12 months
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Clémence Leung, MD、University Hospital, Toulouse
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2026年10月1日
初级完成 (估计的)
2029年10月1日
研究完成 (估计的)
2029年10月1日
研究注册日期
首次提交
2026年9月10日
首先提交符合 QC 标准的
2026年9月10日
首次发布 (实际的)
2026年9月16日
研究记录更新
最后更新发布 (实际的)
2026年9月16日
上次提交的符合 QC 标准的更新
2026年9月10日
最后验证
2026年9月1日
更多信息
与本研究相关的术语
其他研究编号
- RC31/25/0444
- PHRC 24-79 (其他赠款/资助编号：French Ministry of Health)
- 2026-525862-23-00 (其他标识符：ID-RCB)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
未定
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