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)
10. září 2026 aktualizováno: 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.
Přehled studie
Postavení
Zatím nenabíráme
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Intervenční
Zápis (Odhadovaný)
39
Fáze
- Fáze 3
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
- Jméno: Clémence Leung, MD
- Telefonní číslo: +33 05 61 77 61 76
- E-mail: leung.c@chu-toulouse.fr
Studijní místa
-
-
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Nîmes, Francie, 30 029
- Nîmes University Hospital
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Kontakt:
- Giovanni Castelnovo, MD
- Telefonní číslo: +33 04 66 68 32 63
- E-mail: giovanni.castelnovo@chu-nimes.fr
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Vrchní vyšetřovatel:
- Giovanni Castelnovo, MD
-
Toulouse, Francie, 31 059
- Pierre Paul Riquet Hospital - Toulouse University Hospital
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Kontakt:
- Clémence Leung, MD
- Telefonní číslo: +33 05 61 77 61 76
- E-mail: leung.c@chu-toulouse.fr
-
Vrchní vyšetřovatel:
- Clémence Leung, MD
-
-
Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ne
Popis
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.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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.
|
|
Experimentální: 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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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
The effect of botulinum toxin on the resting tremor of the upper limb refractory to treatments
Časové okno: 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.
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7,5 months
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
The effect of botulinum toxin on the resting tremor: evolution evaluated by the investigator
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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.
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7,5 months
|
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The effect of botulinum toxin on the postural tremor: evolution evaluated by the investigator
Časové okno: 7,5 months
|
It will be assessed by the change score at the CGI-C investigator scale, at six weeks post-injection.
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7,5 months
|
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The effect of botulinum toxin on the postural tremor: severity evaluated by the investigator
Časové okno: 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
Časové okno: 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
Časové okno: 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.
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7,5 months
|
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The effect of botulinum toxin on the postural tremor: patient-assessed severity
Časové okno: 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
Časové okno: 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.
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12 months
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The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): amplitude
Časové okno: 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.
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7,5 months
|
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The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): frequency
Časové okno: 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
Časové okno: 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
Časové okno: 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.
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7,5 months
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The safety of use for botulinum toxin: muscle weakness (1)
Časové okno: 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)
Časové okno: 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.
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7,5 months
|
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The safety of use for botulinum toxin: adverse events
Časové okno: 12 months
|
It will be assessed by all the adverse events collected during the study.
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12 months
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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The factors associated with good response to botulinum toxin treatment
Časové okno: 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.
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12 months
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Clémence Leung, MD, University Hospital, Toulouse
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Odhadovaný)
1. října 2026
Primární dokončení (Odhadovaný)
1. října 2029
Dokončení studie (Odhadovaný)
1. října 2029
Termíny zápisu do studia
První předloženo
10. září 2026
První předloženo, které splnilo kritéria kontroly kvality
10. září 2026
První zveřejněno (Aktuální)
16. září 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
16. září 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
10. září 2026
Naposledy ověřeno
1. září 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- RC31/25/0444
- PHRC 24-79 (Jiné číslo grantu/financování: French Ministry of Health)
- 2026-525862-23-00 (Jiný identifikátor: ID-RCB)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
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