Effect of Botulinum Toxin on Resting Tremor of the Refractory Upper Limb in Parkinsonians (TOX PARK)
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
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, the investigators 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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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, the investigators 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. The investigators 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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 3
Contactos e Locais
Contato de estudo
- Nome: Clémence Leung, MD
- Número de telefone: +33 05 61 77 61 76
- E-mail: leung.c@chu-toulouse.fr
Locais de estudo
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Nîmes, França, 30 029
- Nîmes University Hospital
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Contato:
- Giovanni Castelnovo, MD
- Número de telefone: +33 04 66 68 32 63
- E-mail: giovanni.castelnovo@chu-nimes.fr
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Investigador principal:
- Giovanni Castelnovo, MD
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Toulouse, França, 31 059
- Pierre Paul Riquet Hospital - Toulouse University Hospital
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Contato:
- Clémence Leung, MD
- Número de telefone: +33 05 61 77 61 76
- E-mail: leung.c@chu-toulouse.fr
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Investigador principal:
- Clémence Leung, MD
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: 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. |
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Experimental: 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. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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The effect of botulinum toxin on the resting tremor of the upper limb refractory to treatments
Prazo: 7,5 months
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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
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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The effect of botulinum toxin on the resting tremor: evolution evaluated by the investigator
Prazo: 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
|
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The effect of botulinum toxin on the resting tremor: severity evaluated by the investigator
Prazo: 7,5 months
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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
Prazo: 7,5 months
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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
Prazo: 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
|
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The effect of botulinum toxin on the postural tremor: evolution evaluated by the investigator
Prazo: 7,5 months
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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
Prazo: 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
|
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The effect of botulinum toxin on the postural tremor: amplitude evaluated by the investigator
Prazo: 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
Prazo: 7,5 months
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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
|
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The effect of botulinum toxin on the postural tremor: patient-assessed severity
Prazo: 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
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The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): duration
Prazo: 12 months
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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
Prazo: 7,5 months
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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
Prazo: 7,5 months
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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. |
7,5 months
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The effect of botulinum toxin on the patient's experience: life quality
Prazo: 7,5 months
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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. |
7,5 months
|
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The effect of botulinum toxin on the patient's experience: daily life activities
Prazo: 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)
Prazo: 7,5 months
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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)
Prazo: 7,5 months
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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
Prazo: 12 months
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It will be assessed by all the adverse events collected during the study. |
12 months
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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The factors associated with good response to botulinum toxin treatment
Prazo: 12 months
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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
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Clémence Leung, MD, University Hospital, Toulouse
Datas de registro do estudo
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Mais Informações
Termos relacionados a este estudo
Palavras-chave
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Outros números de identificação do estudo
- RC31/25/0444
- PHRC 24-79 (Número de outro subsídio/financiamento: French Ministry of Health)
- 2026-525862-23-00 (Outro identificador: ID-RCB)
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